The SR (serine- and arginine-rich) family proteins and SR-related proteins are important regulators of pre-mRNA splicing. SRRP53 (for SR-related protein of 53kDa) is required in the second step of pre-mRNA splicing and also regulates alternative splicing in a concentration-dependent manner [
]. SRRP53, also known as RSRC1, may also be required for regulation of PIAS1-mediated estrogen receptor beta SUMOylation [].
This is a family of plant antifungal proteins, including defensin-like protein 20-28. It has insecticidal and antifungal activity against certain plant pathogens [
,
,
].
This entry consist of uncharacterised proteins from bacteria, such as YqeY from Bacillus subtilis, and Aim41/YOR215C from yeast. Altered inheritance of mitochondria protein 41 (Aim41/YOR215C) is a protein of unknown function. It was detected in highly purified mitochondria in high-throughput studies, and null mutant displays reduced frequency of mitochondrial genome loss [
]. Aim41/YOR215C is not an essential gene.
Ribosomal protein L25 is an RNA binding protein, that binds 5S rRNA [
,
]. Ribosomal protein L25 has a long-form and a short-form. The long-form is represented by the general stress protein Ctc of Bacillus subtilis, which has now been localised to ribosomes [
], and ribosomal protein TL5 of Thermus thermophilus. Ribosomal protein L25 of Escherichia coli and Haemophilus influenzae appear to be orthologous, but consist only of the N-terminal half of Ctc and TL5. Both short (L25-like) and full-length (CTC-like) members of this family bind the E-loop of bacterial 5S rRNA [,
]. Eukaryotes contain a protein called L25, which is not homologous to bacterial L25, but rather to bacterial L23.
This is a group of animal peptidoglycan recognition proteins homologous to Bacteriophage T3 lysozyme [
]. The bacteriophage molecule, but not its moth homologue, has been shown to have N-acetylmuramoyl-L-alanine amidase activity. One member, Tag7, is a cytokine [].
This entry represents tail sheath proteins from various bacteriophages [
,
], including GpL from Bacteriophage Mu [] and Gp18 from Bacteriophage T4 [,
].
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 [
]. Members of this protein family are cas, or CRISPR-associated, proteins. They are found within cas gene clusters that are adjacent to CRISPR DNA repeats in two members of the order Bacteroidales, Porphyromonas gingivalis W83 and Bacteroides forsythus ATCC 43037.
DNA-packaging protein gp3 (terminase small subunit) is involved in DNA packing in bacteriophage. It contains a channel where DNA is bound and passed to DNA-packaging protein gp2 (terminase large subunit) [
].
Eukaryotic P1 and P2 are functionally equivalent to the bacterial protein L7/L12, but are not homologous to L7/L12. P2 is located in the L12 stalk, with proteins P1, P0, L11, and 28S rRNA. P1 and P2 are the only proteins in the ribosome to occur as multimers, always appearing as sets of heterodimers. Eukaryotes have four copies (two heterodimers), while most archaeal species contain six copies of L12p (three homodimers). Bacteria may have four or six copies of L7/L12 (two or three homodimers) depending on the species [
,
,
]. Experiments using S. cerevisiae P1 and P2 indicate that P1 proteins are positioned more internally with limited reactivity in the C-terminal domains, while P2 proteins seem to be more externally located and are more likely to interact with other cellular components []. In lower eukaryotes, P1 and P2 are further subdivided into P1A, P1B, P2A, and P2B, which form P1A/P2B and P1B/P2A heterodimers []. Some plants have a third P-protein, called P3, which is not homologous to P1 and P 2 [].In humans, P1 and P2 are strongly autoimmunogenic. They play a significant role in the etiology and pathogenesis of systemic lupus erythema (SLE). In addition, the ribosome-inactivating protein trichosanthin (TCS) interacts with human P0, P1, and P2, with its primary binding site in the C-terminal region of P2. TCS inactivates the ribosome by depurinating a specific adenine in the sarcin-ricin loop of 28S rRNA [
].This entry represents the eukaryotic large ribosomal protein P2.
This family consists of several bacterial membrane proteins, including GlpM Pseudomonas aeruginosa and YdgC from
E. coli. GlpM may play a role in alginate biosynthesis [
]. The function of inner membrane protein YdgC is not clear [].
This family includes a group of Leucine rich-repeat (LRR) receptor-like proteins (RLP) from plants. In Arabidopsis, 57 members have been described, some of them are known to be involved in basal developmental processes, whereas others are involved in defence responses [
]. This family represents a group of RLPs including RLP23 from Arabidopsis, which is a component of the RLP23-SOBIR1-BAK1 complex that mediates NLP-triggered immunity [,
]. RLP42 recognizes fungal endopolygalacturonases (PGs) and acts as a novel microbe-associated molecular pattern receptor []. Receptor-like protein 9DC3/9DC2 and Cf-9 homologue from Solanum pimpinellifolium are also included in this family. 9DC3 is involved in plant defense; it confers resistance to the fungal pathogen C.fulvum through recognition of the AVR9 elicitor protein [].
The Escherichia coli nucleoid contains DNA in a condensed but functional form. Analysis of proteins released from isolated spermidine nucleoids after treatment with DNase I revealed significant amounts of two proteins not previously detected in wild-type E. coli. Partial amino-terminal sequencing has identified them as the products of rdgC and yejK. These proteins are strongly conserved in Gram-negative bacteria, suggesting that they have important cellular roles [
].This entry represents the product of gene yejK, nucleoid associated protein NdpA.
This entry represents a group of putative transmembrane proteins. The protein is only approximately 130 amino acids in length. The function is unknown.
The YycFG two-component system is the only signal transduction system in Bacillus subtilis known to be essential for cell viability. This system is highly conserved in low-G+C Gram-positive bacteria, regulating important processes such as cell wall homeostasis, cell membrane integrity, and cell division. Four other genes, yycHIJK, are organised within the same operon with yycF and yycG in B. subtilis. This entry represents a domain found in the YycH proteins. YycH plays a role in signal transduction and is found immediately downstream of the essential histidine kinase YycG. YycG forms a two component system together with its cognate response regulator YycF. PhoA fusion studies have shown that YycH is transported across the cytoplasmic protein. It is postulated that YycH functions as an antagonist to YycG [
]. The molecule is made up of three domains, and has a novel three-dimensional structure. The N-terminal domain features a calcium binding site and the central domain contains two conserved loop regions [].YycI and YycH proteins interact to control the activity of the YycG kinase. Both YycI and YycH proteins are localized outside the cytoplasm and attached to the membrane by an N-terminal transmembrane sequence. Bacterial two-hybrid data showed that the YycH, YycI, and the kinase YycG form a ternary complex. The data suggest that YycH and YycI control the activity of YycG in the periplasm and that this control is crucial in regulating important cellular processes
[,
].
This family consists of several Geminiviridae R3 (or V3) proteins of around 90 residues in length. It may be involved in the viral transport within, and between cells [
].
DsbA is a double stranded binding protein found in bacteriophage T4 which is involved in transcriptional regulation. DsbA, along with other viral proteins, interacts with the host RNA polymerase core enzyme enabling initiation of transcription. DsbA acts as an enhancer protein of late genes in vitro. The protein consists of mainly alpha helices [
].
This is a highly conserved set of proteins which contains three pairs of cysteine residues within a length of 42 amino acids and is rich in proline residues towards the N terminus. It includes a membrane protein that has been found to be highly expressed in the mouse brain and consequently, several members have been assigned as brain protein i3 (Bri3) [
]. Their function is unknown but they appear to play a role in TNF-induced cell death [].
Retroviral matrix proteins (or major core proteins) are components of envelope-associated capsids, which line the inner surface of virus envelopes and are associated with viral membranes []. Matrix proteins are produced as part of Gag precursor polyproteins. During viral maturation, the Gag polyprotein is cleaved into major structural proteins by the viral protease, yielding the matrix (MA), capsid (CA), nucleocapsid (NC), and some smaller peptides. Gag-derived proteins govern the entire assembly and release of the virus particles, with matrix proteins playing key roles in Gag stability, capsid assembly, transport and budding. Although matrix proteins from different retroviruses appear to perform similar functions and can have similar structural folds which predominantly consist of four closely packed α-helices that are interconnected through loops, their primary sequences can be very different []. This superfamily represents structurally homologous matrix proteins from different retroviruses, their structure consisting of four-five alpha helices in a right-handed superhelix. Retroviral matrix proteins bearing this structure have been isolated from Human immunodeficiency virus (HIV), Simian immunodeficiency virus (SIV-cpz), Human T-lymphotropic virus 1, Human T-cell leukemia virus 2 (HTLV-2), Mason-Pfizer monkey virus (MPMV) (Simian Mason-Pfizer virus), Rous sarcoma virus (RSV), Equine infectious anemia virus (EIAV), and Moloney murine leukemia virus (MoMLV). This entry also identifies matrix proteins from several eukaryotic endogenous retroviruses, which arise when one or more copies of the retroviral genome becomes integrated into the host genome [
].
This is a small, rapidly-evolving domain predicted to possess a compact, four-helix structure. Along with a gene encoding a TPR repeat region fused to a CASPASE domain and a gene encoding the CATRA module (CATRA-N CATRA-C) C-terminally fused to a diverse range of conflict effector domains, forms the three gene island making up the CATRA conflict systems. Plays a possible inhibitory role in the CATRA system which is relieved upon sensing of an invasive molecule or is directly cleaved by the CASPASE domain [
].
This family includes Kiwa protein KwaB from E.coli, a component of antiviral defense system Kiwa, composed of KwaA and KwaB. The expression of Kiwa in E.coli (strain MG1655) confers resistance to phages lambda and SECphi18 [
].This family includes a phylogenetically broad range of bacteria associated with the human gut microbiome. A member of this family from Lactobacillus casei CRL 705 is part of the gene cluster involved in synthesis of bacteriocin toxin [
].
Mobilization protein B (MobB) contains a putative membrane-spanning domain, and might be involved in anchoring or presenting MobA, and the covalently-linked plasmid DNA, to the conjugative pore for subsequent export. In agreement with this, MobB has been shown to be associated with the membrane. Deletion of the membrane-spanning domain disrupts this association and decreases the frequency of both type IV transport and plasmid mobilization. MobB is one out of three proteins encoded by RSF1010 that are required for its mobilization along with MobA and MobC [
]. MobB encoded by the broad-host-range plasmid R1162 is required for its efficient transfer by conjugation. The C-terminal half of the protein contains a membrane domain essential for transfer, while the other, functionally active region of MobB, identified by mutagenesis, is at the N-terminal end. One mutation affecting this region inhibits replication, suggesting that this part of the protein is contacting and sequestering the relaxase-linked primase. A model that represents MobB molecules as anchored in the membrane at one end and engaging the relaxase at the other. This arrangement is suggested to increase the transfer frequency by raising the probability of contact between the relaxase and the membrane-embedded, coupling protein for type IV secretion [].
This family is composed of five highly homologous small secreted proteins, TAFA1-5. These proteins contain conserved cysteine residues at fixed positions, and are distantly related to MIP-1alpha, a member of the CC-chemokine family. The FAM19/TAFA proteins are predominantly expressed in specific regions of the brain, and are postulated to function as brain-specific chemokines or neurokines that act as regulators of immune and nervous cells [
]. Mouse TAFA2 is involved in neuronal survival and neurobiological functions []. TAFA5 has been shown to inhibit postinjury neointima formation via sphingosine-1-phosphate receptor 2-G12/13-RhoA signaling [].
This entry represents a group of animal proteins, including TAFA-5 from mammals. TAFA-5 is a secreted protein distantly related to the CC-chemokine family. It has been shown to inhibit postinjury neointima formation via sphingosine-1-phosphate receptor 2-G12/13-RhoA signaling [
]. Together with its target receptor FPR2 can negatively regulate osteoclast formation [].
This entry includes protein I (also known as accessory protein N2) from bovine enteritic coronavirus-F15 strain (BECV-F15) and related Embecoviruses (A lineage) including murine hepatitis virus [
]. The gene encoding protein I is included in the N gene as an alternative ORF []. Protein I appears to have no homologous proteins in Sarbecovirus lineage B, which includes Severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) and SARS-CoV-2 (2019 novel coronavirus, 2019-nCoV). BECV-F15 protein I is not essential for viral replication. It is related to the ORF8b accessory protein of Middle East respiratory syndrome-related coronavirus (MERS-CoV) and other related merbecoviruses (C lineage); the gene encoding ORF8b is an internal ORF that is overlapped by the N (nucleocapsid) protein gene (ORF8a) [,
,
,
].
This entry represents short coiled-coil protein (SCOC). In human, SCOC is required for autophagosome formation during amino acid starvation. It forms a starvation-sensitive trimeric complex with UVRAG (UV radiation resistance associated gene) and FEZ1 and may regulate ULK1 and Beclin 1 complex activities [
].
This protein family represents Taxis protein CheF1/F2 from Halobacterium salinarum and similar proteins found in archaea. CheF1/2 are archaea-specific adaptor proteins that link the bacterial-like chemotaxis signal transduction system to the archaeal motility machinery [
,
].CheF1 interact with the chemotaxis proteins CheY, CheD and CheC2 as well as the flagella-accessory proteins FlaCE and FlaD, and is essential for any tactic response. This protein is conserved in almost all chemotactic archaea.CheF2 is found in a very limited set of haloarchaea and is thought to have a less important role in chemotaxis [
].
This family represents a group of proteins that bind and transfer iron-sulfur (Fe-S) clusters to target proteins and are required for Fe-S cluster assembly. They belong to the conserved family of P-loop ATPases. Iron-sulfur protein NUBPL, an IND1 homologue, is required for the assembly of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) [
,
]. Also included in this family is Fe-S cluster assembly factor HCF101 from Arabidopsis, which specifically assembles 4Fe-4S clusters and transfers them to the chloroplast PSI and ferredoxin-thioredoxin (FTR) complexes [,
]. Iron-sulfur cluster carrier proteins APBC from Bacteria and Archaea are also included in this family [].
This family of proteins is transcribed anti-sense along the DNA to the Parkin gene product and the two appear to be transcribed under the same promoter. The protein has predicted α-helical and β-sheet domains which suggest its function is in the ubiquitin/proteasome system [
]. Mutations in parkin are the genetic cause of early-onset and autosomal recessive juvenile parkinsonism.
Macroautophagy is a bulk degradation process induced by starvation in eukaryotic cells. In yeast, 15 Atg proteins coordinate the formation of autophagosomes. The pre-autophagosomal structure contains at least five Atg proteins: Atg1p, Atg2p, Atg5p, Aut7p/Atg8p and Atg16p, found in the vacuole [
,
]. The C-terminal glycine of Atg12p is conjugated to a lysine residue of Atg5p via an isopeptide bond. During autophagy, cytoplasmic components are enclosed in autophagosomes and delivered to lysosomes/vacuoles. Autophagy protein 16 (Atg16) has been shown to bind to Atg5 and is required for the function of the Atg12p-Atg5p conjugate []. Autophagy protein 5 (Atg5) is directly required for the import of aminopeptidase I via the cytoplasm-to-vacuole targeting pathway [].Autophagy protein 17 (Atg17) forms complex with Atg29 and Atg31, and this complex is critical for both PAS (preautophagosomal structure) formation and autophagy [
].
This entry represents a family of proteins that can be found in (and are an essential part of) actinomycete integrative and conjugative elements (AICEs), including Replication initiator protein from Streptomyces ambofaciens (RepSA), which is essential for pSAM2 replication [
,
].
This entry represents flotillin-like protein FloA from bacteria.Bacterial flotillin-like proteins are found in membrane microdomains that may be equivalent to eukaryotic membrane rafts [
]. Similarly to eukaryotic flotillin proteins, flotillins in bacteria play an essential role in organizing and maintaining the correct architecture of the functional membrane microdomains [,
]. Bacillus subtilis has two flotillin paralogs, FloT and FloA. The absence of one of the flotillins has only minor effects, but the absence of both proteins has very severe effects: loss of proper cell shape, a defect in cell division [].
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 archaeal S27ae protein, which is a component of the 30S subunit.
This entry includes WDL7 from Arabidopsis and related proteins. WDL7 is a TPX2 C-terminal domain containing protein. Similar to WVD2 and other WVD2-like proteins, it contains the KLEEK-motif, which is typical for microtubule-binding proteins [
]. The function of WDL7 is not clear.
This entry represents the nucleocapsid protein from bovine, porcine and equine toroviruses. It is the major structural component of virions associating with the virion genomic RNA.
F-box proteins regulate a number of cellular processes, including cell cycle transition, transcriptional regulation and signal transduction, by playing roles in Skp1p-cullin-F-box protein (SCF) complexes or non-SCF complexes []. F-box proteins have also a role of receptors recruiting substrates into a Skp1/Cdc53/Cdc34 complex for ubiquitination []. The two largest classes of F-box proteins either contain WD-40 repeats like Cdc4 or leucine-rich repeats (LRR) [].The function of At5g39250 is not clear. It has been found to interact with ASK1, indicating that it might be a component of the SCF complex [
].
This entry represents a group of plant calcium-binding proteins, including KRP1/PBP1/KIC from Arabidopsis. KIC interacts with kinesin-like calmodulin binding protein (KCBP) and modulates its activity in response to changes in cytosolic Ca2 and regulates trichome morphogenesis [
].
This entry represents a group of proteins from plants and bacteria, including At5g03900 from Arabidopsis. At5g03900 is an uncharacterised chloroplastic protein.
This family includes the colicin M immunity protein Cmi, and the protein of unknown function YebF. Cmi protects cells from the colicin M toxin, though the mechanism by which it achieves this is not known [
]. The protein forms an α-β fold and contains a disulphide bond that is essential for function []. Although the function of YbeF is not known, it is secreted by E. coli, and contains the two conserved cysteine residues responsible for the disulphide bond in Cmi [].
Cse60 is expressed during sporulation in Bacillus subtilis. Transcription commences around 2h after the start of sporulation and had an absolute requirement for the transcription factor sigmaE. Maximal expression of cse60 further depended on the DNA-binding protein SpoIIID. Cse60 is an acidic product of only 60 residues, whose function is not known [
].
This entry includes Dr1 homologues from plants. They are putative transcription factors. Human Dr1 has been shown to interact with TATA-binding protein (TBP) and block its ability to activate transcription [
]. Arabidopsis Dr1 may affect the regulatory pathway for sexual development [].
This family represents the transmembrane protein 230 (TMEM230) which is involved in trafficking and recycling of synaptic vesicles. Mutations in this protein lead to vesicle trafficking defects associated with Parkinson's disease pathogenesis [
].
The Bacillus subtilis YqaH protein is encoded within a cryptic phage-like region of the chromosome known as the skin element. It is part of the YqaF-YqaN operon, whose expression is negatively regulated by the skin repressor protein SknR. Overexpression of YqaH and YqaM is lethal to the cell, while overexpression of either YqaH and YqaM on their own leads to cell filamentation and abnormal chromosome segregation [
,
]. Yeast two-hydbrid studies suggest that these effects occur via the interaction of YqaH and YqaM with DNA replication proteins DnaA and DnaC, respectively.
This entry represents a group of plant cGTPases, including AtNOA1 from Arabidopsis and OsNOA1 (Os02g01440) from rice. They share homology with bacterial protein YqeH, a circularly permuted GTPase (cGTPase). AtNOA1 (also known as RIF1) has GTPase activity and targets chloroplasts [
]. It is essential for proper chloroplast ribosome assembly and/or translation in plants [].
This entry represents a group of plant fatty-acid-binding proteins, including AtFAP1 from Arabidopsis. The function of AtFAP1 is not clear. Despite its similarity with chalcone isomerase (CHI), AtFAP1 has substitutions at nearly all of the critical catalytic positions of AtCHI, and is devoid of catalytic activity [
]. This entry also includes CHIL1 from Humulus lupulus (European hop). CHIL1 is involved in DMX (demethylxanthohumol) biosynthesis [].
This entry represents a group of plant proteins, including DYAD from Arabidopsis and AMEIOTIC 1 from Zea mays (AM1) and Oryza sativa (OsAM1). DYAD, also known as SWITCH1, is required for the establishment of sister chromatid cohesion and for bivalent formation at meiosis [
]. It may also be required for meiotic recombination initiation []. AM1 plays an important role in multiple early meiotic processes and may be required for the initiation of meiosis []. OsAM1 has a coiled-coil domain in its central region, it is required for the leptotene-zygotene transition step in meiocytes and plays an important role in the building the proper chromosome structure at the beginning of meiosis [].
This entry consists of proteins from tailed bacteriophages (Caudovirales) and bacteria, including Uncharacterized protein RP532 from Rickettsia prowazekii (strain Madrid E). The characteristics of the protein distribution suggest prophage matches. Members of this family are thought to be membrane proteins.
This entry represents a group of plant regulatory proteins, including NPR1-4 from Arabidopsis. NPR1 is a central regulator of salicylic-acid (SA)-mediated defense signaling in Arabidopsis. It contains a BTB/POZ domain at the N-terminal and an ankyrin-repeat domain in the central region. It binds to TGA1, a member of the TGA family of transcription factors that activate SA-responsive elements in the promoters of PR (PATHOGENESIS-RELATED) genes. It also has cytosolic function in cross-communication between SA- and JA-dependent defense signaling pathways [
]. NPR1 is functionally conserved in diverse plant species, including rice (Oryza sativa L.) []. NPR3 and NPR4 have also been shown to be required for basal defense against pathogens [,
].
This entry represents a group of plant BTB/POZ domain and ankyrin repeat-containing proteins, including NPR5/6 from Arabidopsis and NOOT1 from Medicago truncatula [
,
].NPR5 and NPR6, also known as BLADE ON PETIOLE 2 and 1 (BOP2/1), regulates Arabidopsis thaliana lateral organ cell fate and polarity through regulation of LOB domain and adaxial-abaxial polarity genes [
]. They function as transcriptional activators during Arabidopsis thaliana leaf formation [,
]. They are also required for maintaining floral fate [].In Gossypium hirsutum BLADE-ON-PETIOLE1 homologue, GhBOP1, is involved in in plant defence against a fungal pathogen [
].
This entry includes GIP1 and GIP1L from plants. GIP1 may act as a coactivator that regulates transcription factors involved in lateral organ development of plants, such as bZIP transcription factors and LBD18 [
,
]. The function of GIP1L is not clear.
The nitrate and nitrite-sensing (NIT) domain is a (~250 aa) sensor domain found in various receptor components of signal transduction pathways from different bacterial lineages [
]. The NIT domain is predicted to be all α-helical in structure []. Proteins containing a NIT domain belong to one of four known classes of prokaryotic signal transduction proteins: intracellular transcription anti-termination regulators, sensor histidine kinases, methyl-accepting chemotaxis proteins, diguanylate cyclases/phosphodiesterases. NIT-containing receptors regulate cellular functions such as gene expression (transcription anti-terminators and histidine kinases), cell motility (chemotaxis receptors), and enzyme activity (diguanylate cyclases/phosphodiesterases), in response to changes in nitrate and/or nitrite concentrations. The NIT domain is found as both an extracellular and an intracellular sensor. The NIT domain can be found in combination with other signalling domains, such as ANTAR, HAMP (
), MCP, Hemerythrins (
), CHASE (
), GGDEF (
), PAS (
), EAL (
), HK (
), GAF, REC and Hpt (
).
The hD52 gene was originally identified through its elevated expression level in human breast carcinoma. Cloning of D52 homologues from other species has indicated that D52 may play roles in calcium-mediated signal transduction and cell proliferation. Two human homologues of hD52, hD53 and hD54, have also been identified, demonstrating the existence of a novel gene/protein family [
]. These proteins have an N-terminal coiled-coil that allows members to form homo- and heterodimers with each other [].
This entry include Protein BREVIS RADIX (BRX) and related proteins such as BRXL1-4 from plants. BRX has been identified through a natural loss-of-function allele in the Arabidopsis accession Umkirch-1 (Uk-1), and results in reduced root meristem size, reduced mature cell size, and thus reduced root growth [
]. BRX has been shown to regulate the growth rate in both the root and shoot. It mediates cross-talk between the auxin and brassinosteroid pathways [,
].Despite the protein sequence similarity between Arabidopsis BRXL proteins, analysis of brx brx-like multiple mutants indicates that functional redundancy of BRXLs is limited [
].
Transmembrane protein 100 (TMEM100) is a two-transmembrane protein highly conserved in vertebrates. It acts as an ALK1 receptor signalling-dependent protein during endothelial differentiation and vascular morphogenesis, and regulates TRPA1-TRPV1 complex that mediates pain signals in dorsal root ganglia neurons [
,
].
This entry represents a group of plant F-box proteins, including At5g50450 and At1g67340 from Arabidopsis. They contain the MYND-type zinc finger. At1g67340 may be the F-box subunit of the SCF E3 complex [
].
This family of proteins are mitochondrial 18kDa proteins that are often misannotated as carbonic anhydrases. It was shown that knockdown of MTP18 protein results in a cytochrome c release from mitochondria and consequently leads to apoptosis [
]. Over expression studies suggest that MTP18 is required for mitochondrial fission [].
This entry represents a group disulfide-isomerases, including PDIA6 from animals, Mpd1 from yeasts and PDI22/PDI23 from Arabidopsis. Protein-disulfide isomerase (PDI) is a resident of the endoplasmic reticulum (ER) that catalyses the formation, reduction, and isomerization of disulfide bonds. PDIA6 is an active oxidoreductase with similar enzymatic properties to other PDIs; however, it doesn't seem to be involved directly in protein folding. Instead, it regulates the unfolded protein response (UPR) through controlling the decay of IRE1alpha signaling via disulfide-dependent association []. Mpd1 have oxidative refolding activity and interacts with Cne1, an integral membrane ER chaperone involved in folding and quality control of glycoproteins [].
Sec22 is an nonessential SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) involved in targeting and fusion of ER-derived transport vesicles with the Golgi complex as well as Golgi-derived retrograde transport vesicles with the ER
[].
This entry includes C2-domain abscisic acid-related protein CAR1-11 from Arabidopsis and GTPase activating protein 1 (OsGAP1) from rice. CARs interact with the PYR/PYL ABA receptors and recruit them to membranes in a Ca2+-dependent manner [
]. OsGAP1 is a soluble protein that can loosely associate with plasma membrane. It can also interact with an unconventional G-protein, OsYchF1, and stimulate its NTPase activities [].
This entry represents a group of plant F-box/kelch-repeat proteins, including KMD1-4 from Arabidopsis. They belong to the kiss me deadly (KMD) family, whose members target type-B ARR proteins for degradation. They form an S-phase kinase-associated PROTEIN1 (SKP1)/Cullin/F-box protein (SCF) E3 ubiquitin ligase complex and directly interact with type-B ARR proteins, which then regulates the transcriptional response to cytokinin [
]. KMD1 (At1g80440, also known as KFB20), KMD2 (AT1G15670, also known KFB01) and KDM4 (also known as SKIP20) interact with four PAL isozymes and mediate their proteolytic turnover via the ubiquitination-26S proteasome pathway [].
The 17kDa protein Skp (also known as OmpH) of Escherichia coli is a homotrimeric periplasmic chaperone for newly synthesised outer-membrane proteins, the X-ray structure of which has been reported at resolutions of 2.35 A and 2.30 A [
,
]. Three hairpin-shaped α-helical extensions reach out by approximately 60 A from a trimerisation domain, which is composed of three intersubunit β-sheets that wind around a central axis. The α-helical extensions approach each other at their distal turns, resulting in a fold that resembles a 'three-pronged grasping forcep'. The overall shape of Skp is reminiscent of the cytosolic chaperone prefoldin, although it is based on a radically different topology. The peculiar architecture, with apparent plasticity of the prongs and distinct electrostatic and hydrophobic surface properties, supports the recently proposed biochemical mechanism of this chaperone: formation of a Skp(3)-Omp complex protects the outer membrane protein from aggregation during passage through the bacterial periplasm.The ability of Skp to prevent the aggregation of model substrates in vitro is independent of ATP. Skp can interact directly with membrane lipids and lipopolysaccharide. These interactions are needed for efficient Skp-assisted folding of membrane proteins [
].The Haemophilus influenzae member of the family, OMP26, is an outer membrane protein that shows significant potential as a vaccine candidate [
]. It is not clear if this protein has undergone adaptive changes in H. influenzae so as to locate to the outer membrane, or if Skp proteins are to some extent peripherally associated with the outer membrane in all species.
Hexon is the major coat protein in type 2 adenoviruses. Hexon forms a homo-trimer, 240 copies of which are present in the capsid, organised so that 12 lie on each of the 20 facets of this structure. The central 9 hexons in a facet are cemented together by 12 copies of protein IX [
]. Protein IX is not neccessarily required for viral replication, but has been shown to affect several processes including DNA-packaging capacity, thermostability, and the transcriptional activity of several promoters. For more information see [].
This entry represents a family of transmembrane proteins, which function as a negative regulator of MYRF in oligodendrocyte differentiation and myelination. Interacts with the C-terminal of MYRF inhibiting MYRF self-cleavage and N-fragment nuclear translocation [
]. The secreted TMEM98 form promotes differentiation of T helper 1 cells (Th1) [].
MEOX1 and MEOX2 are homeodomain transcription factors that have been shown to be partially functionally redundant during development. They regulate the cyclin dependent kinase inhibitors p21 and p16 in vascular endothelial cells [
]. Nevertheless, MEOX1 also plays important, non-redundant roles in maintaining sclerotome polarity and the formation of cranio-cervical joints []. Mutations in the MEOX1 gene cause Klippel-Feil syndrome 2, autosomal recessive (KFS2), a skeletal disorder characterised by congenital fusion of cervical vertebrae [,
].
Bacteriocins are antibacterial proteinaceous compounds produced by bacteria. In Gram-positive bacteria, they are divided into four classes. Within the class II, constituted by non-modified peptides produced mainly by lactic acid bacteria, bacteriocins of the subclass IIa (also known as pediocin-like bacteriocins), such as mesentericin Y105, are of particular interest. They are active against the foodborne pathogen Listeria monocytogenes and share a similar primary structure, with a conserved N-terminal motif (YGNGV). Subclass IIa bacteriocins induce membrane permeabilization of sensitive strains [
]. Class-IId contains the one-peptide non-cyclic bacteriocins that show no sequence similarity to the pediocin-like bacteriocins, andinclude lactococcin A (LcnA) [
].The translocation of most of the class II bacteriocins requires a type I secretion system which is composed of maturation and secretion protein and an accessory factor. MesD and MesE encode the dedicated transport system of mesentericin Y105 [
]. Secretion and maturation of LcnA depends on the two membrane proteins LcnC and LcnD []. This family consist of accessory factors such as MesE and LcnD. Their function remains unclear, but they are required for full production of these bacteriocins [,
].
This entry includes [3-methyl-2-oxobutanoate dehydrogenase [lipoamide]] kinase (BCKDK) and [Pyruvate dehydrogenase (acetyl-transferring)]kinase (PDK). BCKDK catalyzes the phosphorylation and inactivation of the branched-chain alpha-ketoacid dehydrogenase complex, the key regulatory enzyme of the valine, leucine and isoleucine catabolic pathways [
].Pyruvate dehydrogenase kinase inhibits the pyruvate dehydrogenase complex by phosphorylation of the E1 alpha subunit, thus contributing to the regulation of glucose metabolism [
].
This entry represents the Rab29/Rab38/Rab32 subfamily. They are members of the Rab family of small GTPases. Human Rab32 was first identified in platelets but it is expressed in a variety of cell types, where it functions as an A-kinase anchoring protein (AKAP) [
]. Rab32 and closely related Rab38 are functionally redundant regulators of melanosomal protein trafficking and melanocyte pigmentation [,
].Ras-related protein Rab29 (also known as RAB7L) is related to Rab32 and Rab38. Rab29 regulates phagocytosis and traffic from the Golgi to the lysosome [
]. It is associated with trans-Golgi network (TGN) and is essential for maintaining the integrity of the TGN. Together with LRRK2, it plays a role in the retrograde trafficking pathway for recycling proteins, such as mannose 6 phosphate receptor (M6PR), between lysosomes and the Golgi apparatus in a retromer-dependent manner []. Rab29, Rab32 and Rab38 can be cleaved by GtgE, which is an effector protein from Salmonella Typhimurium that modulates trafficking of the Salmonella-containing vacuole (SCV) [
]. By targeting these GTPases, GtgE allows survival of the pathogen by preventing the delivery of antimicrobial factors to the SCV [].
T-complex testis-expressed protein 4 (Tctex4, ZNRD1-AS1) has been identified in mice as a protein that may be involved in male sterility [
]. Tctex4 interacts with protein kinase CK2beta subunit [].
This family of proteins can be found in plants and Cyanobacteria, including PG18 (At4g13200) from Arabidopsis and thylakoid protein sll1769 from Synechocystis sp. [
]. PG18 is a plastoglobular protein involved in chloroplast function and thylakoid formation [].
Nucleolar protein 9 (NOP9) is an RNA-binding nucleolar protein found in yeast and required for pre-rRNA processing. It is a component of both the 90S pre-ribosome and the pre-40S ribosome [
]. This entry also includes APUM23 from Arabidopsis. APUM23 is a nucleolar PUF protein involved in pre-rRNA processing [].
The DNA sequence of the entire colicin E2 operon has been determined [
].The operon comprises the colicin activity gene (ceaB), the colicin immunity
gene (ceiB) and the lysis gene (celB), which is essential for colicinrelease from producing cells [
]. A putative LexA binding site is locatedupstream from ceaB, and a rho-independent terminator structure is located
downstream from celB []. Comparison of the amino acid sequences of colicinE2 and cloacin DF13 reveal extensive similarity. These colicins have
different modes of action and recognise different cell surface receptors;the two major regions of heterology at the C terminus, and in the C-terminal
end of the central region are thought to correspond to the catalytic and receptor-recognition domains, respectively [
]. Sequence similarities between colicins E2, A and E1 [
] are less striking.The colicin E2 (pyocin) immunity protein does not share similarity with
either the colicin E3 or cloacin DF13 [] immunity proteins. By contrast,the lysis proteins of the ColE2, ColE1 and CloDF13 plasmids are almost
identical except in the N-terminal regions, which themselves are similar tolipoprotein signal peptides [
]. Processing of the ColE2 prolysis proteinto the mature form is prevented by globomycin, a specific inhibitor of the
lipoprotein signal peptidase []. The mature ColE2 lysis protein is locatedin the cell envelope [
].
Norrie disease is a severe, X-linked, recessive neurodevelopmental disorder
characterised by progressive atrophy of the eyes, deafness and mental retardation [
]. The Norrie disease gene is expressed in retina, choroidand foetal brain [
]. X-linked Familial Exudative Vitreoretinopathy (XLFEVR)is a hereditary eye disorder that affects both the retina and the vitreous
body and is characterised by abnormal vascularisation of the peripheralretina. It has been shown that phenotypes of both XLFEVR and Norrie
disease can result from mutations in the same gene [].Norrie disease protein (NDP) is thought to have a tertiary structure
similar to that of transforming growth factor beta (TGF beta). Molecular modelling studies have suggested that NDP is a member of anemerging family of growth factors containing a cystine knot motif [
].NDP is thought to be involved in a pathway that regulates neural cell
differentiation and proliferation, and may have a role in neuroectodermal cell-cell interaction.
The circumsporozoite (CS) protein is the most prominant surface antigen on
the sporozoite of the malaria parasite, Plasmodium spp. The sporozoite isthe infectious stage of the Plasmodium life cycle, the form in which malaria
is passed from the mosquito vector to the mammalian host []. Antibodies tothis protein are used in the field to detect exposure to malaria [
] and it is a target for several vaccines [
].The sequence of the CS protein consists of head and tail regions, which are
largely conserved, and a large set of low-complexity repeats, which are variant across strain and species [
]. The C-terminal region is probably used for anchoring the protein to the cell membrane, while the centralrepeat sequences would be the surface antigen of the organism. The repeats,
which encode the immunodominant epitope of the CS protein (see ), diverge more
rapidly than the remainder of the gene. It is thought that the maintenanceand evolution of the repeats is achieved via a mechanism that acts not at
the protein level, but rather directly on the DNA sequence [].
CXADR-like membrane protein (CLMP), also known as ACAM, belongs to the CTX family, whose members are type I transmembrane proteins within the immunoglobulin superfamily (IgSF). It is a component of epithelial tight junctions [
]. It has been implicated in adipocyte maturation and development of obesity []. Mutations of the CLMP gene cause Congenital Short Bowel Syndrome (CSBS) [].
This entry contains bacterial antiholin-like LrgA proteins, which have been shown to modulate murein hydrolase activity [
]. Together with holin-like CidA, LrgA function to control cell death and lysis during biofilm development [
].
This entry represents CidA, which increases the activity of extracellular murein hydrolases possibly by mediating their export via hole formation. It is inhibited by the antiholin-like proteins LrgAB. In an unstressed cell, the LrgAB products probably inhibit the function of the CidAB proteins. When a cell is stressed by the addition of antibiotics or by other factors in the environment, the CidAB proteins possibly oligomerise within the bacterial cell membrane, creating lesions that disrupt the proton motive force, which in turn results in loss of cell viability. These lesions are also hypothesised to regulate the subsequent cell lysis by either allowing the murein hydrolases access to the cell wall substrate and/or regulating their activity by a possible change in the cell wall pH that results from loss of membrane potential [
].
SH2B family contains three members of adaptor proteins: SH2B1, 2 and 3 [
]. Typical SH2B proteins contain a SH2 (Src homology 2) and a PH (pleckstrin homology) domain. They serve as adaptors involved in signalling by the receptors for growth factors, such as insulin-like growth factor 1, platelet-derived growth factor and nerve growth factor [].
Nucleoredoxin-like protein 1 (Nxnl1, also known as RdCVF) is a trophic factor with therapeutic potential that is involved in cone photoreceptor survival []. It may slow down cone degeneration [] and play an important role in photoreceptor maintenance and resistance to retinal oxidative stress [].
Colicin immunity proteins are plasmid encoded proteins necessary for protecting the cell against colicins. Colicins are toxins released by bacteria during times of stress [
].
Clag (cytoadherence linked asexual gene) is a malaria surface protein which has been shown to be involved in the binding of Plasmodium falciparum infected erythrocytes to host endothelial cells, a process termed cytoadherence. The cytoadherence phenomenon is associated with the sequestration of infected erythrocytes in the blood vessels of the brain, cerebral malaria. Clag is a multi-gene family in P. falciparum with at least 9 members identified to date. Orthologous proteins in the rodent malaria species Plasmodium chabaudi suggest that the gene family is found in other malaria species and may play a more generic role in cytoadherence.
Nucleoredoxin-like protein 2 (Nxnl2, also known as RdCVF2) is a trophic factor with therapeutic potential that are involved in cone photoreceptor survival [
]. It may be involved in the maintenance of both the function and the viability of sensory neurons, including photoreceptors and olfactory neurons [,
].
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 the Csc2 family of Cas proteins that are strictly associated with the Cyano subtype of CRISPR/Cas locus and found in several species of Cyanobacteria and several archaeal species. This family is designated Csc2 for CRISPR/Cas Subtype Cyano protein 2, as it is often the second gene upstream of the core cas genes, cas3-cas4-cas1-cas2 [
].
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 the Csc1 family of Cas proteins that are strictly associated with the Cyano subtype of CRISPR/Cas locus and found in several species of Cyanobacteria and several archaeal species. This family is designated Csc1 for CRISPR/Cas Subtype Cyano protein 1, as it is often the first gene upstream of the core cas genes, cas3-cas4-cas1-cas2 [
].
This entry includes Harmonin-binding protein USHBP1 also known as MCC2) and colorectal mutant cancer protein known as MCC. MCC has been found to suppresses cell proliferation and the Wnt/b-catenin pathway in colorectal cancer cells [
,
]. It may works as a scaffold protein regulating cell movement and able to bind Scrib, beta-catenin and NHERF1/2 []. MCC1 inhibits DNA binding of b-catenin/TCF/LEF transcription factors, and it is involved in cell migration independently of RAC1, CDC42 and p21-activated kinase (PAK) activation [,
,
].MCC2 protein binds the first PDZ domain of AIE-75 with its C-terminal amino acids -DTFL. A possible role of MCC2 as a tumour suppressor has been put forward. The carboxyl terminus of the predicted protein was DTFL which matched the consensus motif X-S/T-X-phi (phi: hydrophobic amino acid residue) for binding to the PDZ domain of AIE-75 [
,
].
This family of plant proteins includes Arabidopsis parting dancers (PTD), a protein that is required for chromosome segregation during meiosis [
]. It is involved in type I crossover formation [].
This entry represents autophagy-related protein 13 (Atg13) from yeasts, animals and plants, which functions in autophagy.Fission yeast autophagy initiation is controlled by the Atg1 kinase complex, which is composed of the Ser/Thr kinase Atg1, the adaptor protein Atg13, and the ternary complex of Atg17-Atg31-Atg29. Atg13 recruits Atg1 to the site of autophagosome formation and enhancing Atg1 kinase activity. Atg13 may have additional functions that are independent of a direct interaction or permanent colocalization with Atg1 []. In vertebrates, the orthologous ULK1 kinase complex contains the Ser/Thr kinase ULK1 and the accessory proteins ATG13, RB1CC1, and ATG101 [
]. Through its regulation of ULK1 activity, Atg13 plays a role in the regulation of the kinase activity of mTORC1 and cell proliferation [].
