This entry represents a group of plant basic leucine zipper proteins (bZIPs), including AtbZIP8 and AtbZIP43. AtbZIP43 may act as positive regulator of BHLH109, which is associated with somatic embryogenesis (SE) induction [
].The basic (region) leucine zippers (bZIPs) are evolutionarily conserved transcription factors in eukaryotic organisms. In plants bZIPs regulate processes including pathogen defence, light and stress signalling, seed maturation and flower development [
]. The bZIP domain consists of a basic DNA-binding region and the adjacent ZIP domain. The ZIP domain consists of heptad repeats of leucine (L) or related hydrophobic amino acids. The DNA-binding region is a basic region of ~16 amino acid residues containing a nuclear localization signal followed by an invariant N-x7-R/K motif that contacts the DNA The heptad repeat of leucines or other bulky hydrophobic amino acids positioned exactly nine amino acids towards the C terminus, creating an amphipathic helix. To bind DNA, two subunits adhere via interactions between the hydrophobic sides of their helices, which creates a superimposing coiled-coil structure. The ability to form homo- and heterodimers is influenced by the electrostatic attraction and repulsion of polar residues flanking the hydrophobic interaction surface of the helices [
]. As bZIPs generally perform as dimers, heterodimerisation results in an enormous regulatory flexibility [].
This entry includes a group of plant proteins, such as QUIRKY and FTIP1/3/4/7 from Arabidopsis [
,
]. These are Multiple C2 domain and Transmembrane region Proteins (MCTPs) which are involved in Ca2 signalling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2 but not phospholipids. QUIRKY may contribute to plant organ organogenesis mediated by the receptor-like kinase STRUBBELIG and may play a role in Ca2-dependent signaling and membrane trafficking [
]. It has been shown to be required for the appropriate spatial expression of several epidermal cell fate regulators []. FTIP1 is involved in the export of FT from the phloem companion cells to the sieve elements through the plasmodesmata. It regulates flowering time under long days []. FTIP3/4 play an essential role in mediating proliferation and differentiation of shoot stem cells []. FTIP7 promotes nuclear translocation of the transcription factor OSH1 and reduces auxin levels at late stage of anther development, after meiosis of microspore mother cells. It is necessary for normal anther dehiscence and seed setting [].
Plasmids may be maintained stably in bacterial populations through the action of addiction modules, in which a toxin and antidote are encoded in a cassette on the plasmid. In any daughter cell that lacks the plasmid, the toxin persists and is lethal after the antidote protein is depleted. Toxin/antitoxin pairs are also found on main chromosomes, and likely represent selfish DNA. Sequences in the seed for this alignment all were found adjacent to toxin genes. Several toxin/antitoxin pairs may occur in a single species. RelE and RelB form a toxin-antitoxin system; RelE cleaves mRNA during translation on the ribosome [
,
,
]. RelB binds and inhibits RelE and it regulates transcription by operator binding and conditional cooperativity controlled by RelE. RelE and RelB form a V-shaped heterotetrameric complex which has a ribbon-helix-helix (RHH) dimerization domain at the apex. [].DinJ is an antitoxin component of a toxin-antitoxin (TA) module. It is a labile antitoxin that counteracts the effect of the YafQ toxin [
]. It forms a heterotetrameric complex with YafQ and the structure of this complex revealed that the N-terminal region of DinJ folds into a ribbon-helix-helix motif that dimerises for DNA recognition, and the C-terminal portion of each DinJ wraps around a YafQ molecule []. Together, they they bind their own promoter, and by analogy to other TA modules probably repress its expression. Cell death governed by the mazEF and dinJ-yafQ TA modules seems to play a role in biofilm formation [,
,
].
This domain is named after Bet v 1, the major birch pollen allergen. Bet v 1 belongs to family 10 of plant pathogenesis-related proteins (PR-10), cytoplasmic proteins of 15-17 kd that are wide-spread among dicotyledonous plants [
]. In recent years, a number of diverse plant proteins with low sequence similarity to Bet v 1 was identified. A classification by sequence similarity yielded several subfamilies related to PR-10 []:Pathogenesis-related proteins PR-10: These proteins were identified as major tree pollen allergens in birch and related species (hazel, alder), as plant food allergens expressed in high levels in fruits, vegetables and seeds (apple, celery, hazelnut), and as pathogenesis-related proteins whose expression is induced by pathogen infection, wounding, or abiotic stress. Hyp-1 (
), an enzyme involved in the synthesis of the bioactive naphthodianthrone hypericin in St. John's wort (Hypericum perforatum) also belongs to this family. Most of these proteins were found in dicotyledonous plants. In addition, related sequences were identified in monocots and conifers.
Cytokinin-specific binding proteins: These legume proteins bind cytokinin plant hormones [].(S)-Norcoclaurine synthases are enzymes catalysing the condensation of dopamine and 4-hydroxyphenylacetaldehyde to (S)-norcoclaurine, the first committed step in the biosynthesis of benzylisoquinoline alkaloids such as morphine [
]. Major latex proteins and ripening-related proteins are proteins of unknown biological function that were first discovered in the latex of opium poppy (Papaver somniferum) and later found to be upregulated during ripening of fruits such as strawberry and cucumber [
]. The occurrence of Bet v 1-related proteins is confined to seed plants with the exception of a cytokinin-binding protein from the moss Physcomitrella patens (
).
Molecular chaperones are a diverse family of proteins that function to protect proteins in the intracellular milieu from irreversible aggregation during synthesis and in times of cellular stress. The bacterial molecular chaperone DnaK is an enzyme that couples cycles of ATP binding, hydrolysis, and ADP release by an N-terminal ATP-hydrolysing domain to cycles of sequestration and release of unfolded proteins by a C-terminal substrate binding domain. In prokaryotes, the grpE protein is a co-chaperone for DnaK, and acts as a nucleotide exchange factor, stimulating the rate of ADP release 5000-fold [
]. DnaK is itself a weak ATPase; ATP hydrolysis by DnaK is stimulated by its interaction with another co-chaperone, DnaJ. Thus the co-chaperones DnaJ and GrpE are capable of tightly regulating the nucleotide-bound and substrate-bound state of DnaK in ways that are necessary for the normal housekeeping functions and stress-related functions of the DnaK molecular chaperone cycle.Members of this family are the chaperone DnaK, of the DnaK-DnaJ-GrpE chaperone system. All members of the seed alignment were taken from completely sequenced bacterial or archaeal genomes and (except for the Mycoplasma sequence) found clustered with other genes of this systems. This entry excludes DnaK homologues that are not DnaK itself, such as the heat shock cognate protein HscA (
). However, it is not designed to distinguish among DnaK paralogs in eukaryotes. Note that a number of DnaK genes have shadow ORFs in the same reverse (relative to dnaK) reading frame, a few of which have been assigned glutamate dehydrogenase activity. The significance of this observation is unclear; the lengths of such shadow ORFs are highly variable as if the presumptive protein product is not conserved.
This entry represents the fourth C2 domain, referred to as C2D, from QUIRKY and related proteins. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions [
,
].This entry includes a group of plant proteins, such as QUIRKY and FTIP1/3/4/7 from Arabidopsis [
,
]. These are Multiple C2 domain and Transmembrane region Proteins (MCTPs) which are involved in Ca2 signalling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2 but not phospholipids. QUIRKY may contribute to plant organ organogenesis mediated by the receptor-like kinase STRUBBELIG and may play a role in Ca2-dependent signaling and membrane trafficking [
]. It has been shown to be required for the appropriate spatial expression of several epidermal cell fate regulators []. FTIP1 is involved in the export of FT from the phloem companion cells to the sieve elements through the plasmodesmata. It regulates flowering time under long days []. FTIP3/4 play an essential role in mediating proliferation and differentiation of shoot stem cells []. FTIP7 promotes nuclear translocation of the transcription factor OSH1 and reduces auxin levels at late stage of anther development, after meiosis of microspore mother cells. It is necessary for normal anther dehiscence and seed setting [].
This entry represents the second C2 domain, referred to as C2B, from QUIRKY and related proteins. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions [
,
].This entry includes a group of plant proteins, such as QUIRKY and FTIP1/3/4/7 from Arabidopsis [
,
]. These are Multiple C2 domain and Transmembrane region Proteins (MCTPs) which are involved in Ca2 signalling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2 but not phospholipids. QUIRKY may contribute to plant organ organogenesis mediated by the receptor-like kinase STRUBBELIG and may play a role in Ca2-dependent signaling and membrane trafficking [
]. It has been shown to be required for the appropriate spatial expression of several epidermal cell fate regulators []. FTIP1 is involved in the export of FT from the phloem companion cells to the sieve elements through the plasmodesmata. It regulates flowering time under long days []. FTIP3/4 play an essential role in mediating proliferation and differentiation of shoot stem cells []. FTIP7 promotes nuclear translocation of the transcription factor OSH1 and reduces auxin levels at late stage of anther development, after meiosis of microspore mother cells. It is necessary for normal anther dehiscence and seed setting [].
This entry represents the third C2 domain, referred to as C2C, from QUIRKY and related proteins. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions [
,
].This entry includes a group of plant proteins, such as QUIRKY and FTIP1/3/4/7 from Arabidopsis [
,
]. These are Multiple C2 domain and Transmembrane region Proteins (MCTPs) which are involved in Ca2 signalling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchoredto membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2 but not phospholipids.
QUIRKY may contribute to plant organ organogenesis mediated by the receptor-like kinase STRUBBELIG and may play a role in Ca2-dependent signaling and membrane trafficking [
]. It has been shown to be required for the appropriate spatial expression of several epidermal cell fate regulators []. FTIP1 is involved in the export of FT from the phloem companion cells to the sieve elements through the plasmodesmata. It regulates flowering time under long days []. FTIP3/4 play an essential role in mediating proliferation and differentiation of shoot stem cells []. FTIP7 promotes nuclear translocation of the transcription factor OSH1 and reduces auxin levels at late stage of anther development, after meiosis of microspore mother cells. It is necessary for normal anther dehiscence and seed setting [].
Zinc fingers are a ubiquitous class of protein domain with considerable variation in structure and function. The FCS-type zinc finger is a highly diverged group of C2-C2 zinc finger which is present in animals, prokaryotes and viruses, but not in plants. It is named after the conserved phenylalanine and serine residues associated with the third cysteine. The FCS-type zinc finger is a structurally diverse family which accommodate both nucleic-protein and protein-protein interaction zinc fingers. The FCS-Like Zinc finger (FLZ) domain is a plant specific domain found in all taxa except algae. FLZ domain containing proteins are bryophytic in origin and this protein family is expanded in higher plants. Although the molecular functions of the FLZ protein family members in general are not well understood, many of the members are attributed to plant growth and development, stress mitigation, sugar signaling and senescence. The FLZ-type zinc finger is likely to be involved in protein-protein interaction [
,
,
].The FLZ-type zinc finger is predicted to form an α-β-alpha secondary structure composed of an N-terminal short α-helix, a beta hairpin followed by a longer C-terminal alpha helix. Four highly conserved cysteine residues in the FLZ-type zinc finger are believed to bind zinc in a tetrahedral coordination [
,
].Some proteins known to contain a FLZ-type zinc finger are listed below [
]:Arabidopsis thaliana MEDIATOR OF ABA-REGULATED DORMANCY 1 (MARD1) or FLZ9, involved in absissic acid (ABA)-mediated seed dormancy and induced during senescence.Arabidopsis thaliana INCREASED RESISTANCE TO MYZUS PERSICAE (IRM1) or FLZ4, constitutive overexpression of IRM1 results in mechanical barriers that make it difficult for M. persicae to reach the phloem and subsequently reduces its population size.Wheat salt related hypothetical protein (TaSRHP), overexpression of TaSHRP results in enhanced resistance to salt and drought stress.
This entry includes a group of acetyltransferases, such as NeuD sialic acid O-acetyltransferase enzymes from Escherichia coli and Streptococcus agalactiae (group B strep) [
,
,
], UDP-N-acetylbacillosamine N-acetyltransferase pglD from Campylobacter jejuni subsp. jejuni [,
] and GDP-perosamine N-acetyltransferase perB from Escherichia coli O157:H7 []. This group is composed of mostly uncharacterized proteins containing an N-terminal helical subdomain followed by a LbH domain. The alignment contains 6 turns, each containing three imperfect tandem repeats of a hexapeptide repeat motif (X-[STAV].-X-[LIV]-[GAED]-X). Proteins containing hexapeptide repeats are often enzymes showing acyltransferase activity [
].The neuD gene is often observed in close proximity to the neuABC genes for the biosynthesis of CMP-N-acetylneuraminic acid (CMP-sialic acid), and NeuD sequences from these organisms were used to construct the seed for this model. Nevertheless, there are numerous instances of sequences identified by this model which are observed in a different genomic context (although almost universally in exopolysaccharide biosynthesis-related loci), as well as in genomes for which the biosynthesis of sialic acid (SA) has not been demonstrated. Even in the cases where the association with SA biosynthesis is strong, it is unclear in the literature whether the biological substrate is SA itself, CMP-SA, or a polymer containing SA. Similarly, it is unclear to what extent the enzyme has a preference for acetylation at the 7, 8 or 9 positions. In the absence of evidence of association with SA, members of this family may be involved with the acetylation of differing sugar substrates, or possibly the delivery of alternative acyl groups. The closest related sequences to this family (and those used to root the phylogenetic tree constructed to create this model) are believed to be succinyltransferases involved in lysine biosynthesis.
Ethylene is an endogenous plant hormone that influences many aspects of plant growth and development. Some defense related genes that are induced by ethylene contain a cis-regulatory element known as the Ethylene-Responsive Element (ERE) [
]. Sequence analysis on various ERE regions has identified a short motif rich in G/C nucleotides, the GCC-box, essential for the response to ethylene. This short motif is recognised by a family of transcrition factors, the ERE binding factors (ERF) [].ERF proteins contain a domain of around 60 amino acids which is also found in the APETALA2 (AP2) protein [
]. This AP2/ERF domain has been shown in various proteins to be necessary and sufficient to bind the GCC-box [
].The structure of the AP2/ERF domain in complex with the target DNA has been solved [
]. The structure resembles that of bacteriophage integrases and the methyl-CpG-binding domain (MBD): a three-stranded β-sheet and an alpha helix almost parallel to the β-sheet. It contacts DNA via Arg and Trp residues located in the β-sheet. Some proteins known to contain an AP2/ERF domain include:Arabidopsis thaliana ERF1 to 6. Tobacco ethylene-responsive element-binding proteins (EREBPs), homologues of ERF proteins. Arabidopsis thaliana AP2 protein. It regulates meristeme identity, floral organ specification and seed coat development. Arabidopsis thaliana C-repeat/dehydration-responsive element (DRE) binding factor 1 (CBF1 or DREB1) and DREB2. They bind a GCC-box-like element found in dehydratation responsive element. Binding to this element mediates cold-inducible transcription. Arabidopsis thaliana and maize abscisic acid (ABA)-insensitive 4 (ABI4) proteins. They bind to a GCC-box-like element found in ABA-responsive genes.Octadecanoid-derivative responsive catharenthus AP2-domain (ORCA2) protein. It binds a GCC-box-like element in the jasmonate responsive element of Str promoter. Tomato Pto-interacting proteins 4 to 6 (Pti4 to Pti6). Pti5 and 6 bind a GCC-box-like element in regulatory regions of various pathogenesis-related (PR) genes. Trichodesmium erythraeum, Tetrahymena thermophila, Enterobacteria phage RB49 and bacteriophage Felix 01 HNH endonucleases. HNH endonucleases are homing endonucleases that move extensively via lateral gene transfer [
]. This entry represents the AP2/ERF domain.
Ethylene is an endogenous plant hormone that influences many aspects of plant growth and development. Some defense related genes that are induced by ethylene contain a cis-regulatory element known as the Ethylene-Responsive Element (ERE) [
]. Sequence analysis on various ERE regions has identified a short motif rich in G/C nucleotides, the GCC-box, essential for the response to ethylene. This short motif is recognised by a family of transcrition factors, the ERE binding factors (ERF) [].ERF proteins contain a domain of around 60 amino acids which is also found in the APETALA2 (AP2) protein [
]. This AP2/ERF domain has been shown in various proteins to be necessary and sufficient to bind the GCC-box [].The structure of the AP2/ERF domain in complex with the target DNA has been solved [
]. The structure resembles that of bacteriophage integrases and the methyl-CpG-binding domain (MBD): a three-stranded β-sheet and an alpha helix almost parallel to the β-sheet. It contacts DNA via Arg and Trp residues located in the β-sheet. Some proteins known to contain an AP2/ERF domain include:Arabidopsis thaliana ERF1 to 6. Tobacco ethylene-responsive element-binding proteins (EREBPs), homologues of ERF proteins. Arabidopsis thaliana AP2 protein. It regulates meristeme identity, floral organ specification and seed coat development. Arabidopsis thaliana C-repeat/dehydration-responsive element (DRE) binding factor 1 (CBF1 or DREB1) and DREB2. They bind a GCC-box-like element found in dehydratation responsive element. Binding to this element mediates cold-inducible transcription. Arabidopsis thaliana and maize abscisic acid (ABA)-insensitive 4 (ABI4) proteins. They bind to a GCC-box-like element found in ABA-responsive genes.Octadecanoid-derivative responsive catharenthus AP2-domain (ORCA2) protein. It binds a GCC-box-like element in the jasmonate responsive element of Str promoter. Tomato Pto-interacting proteins 4 to 6 (Pti4 to Pti6). Pti5 and 6 bind a GCC-box-like element in regulatory regions of various pathogenesis-related (PR) genes. Trichodesmium erythraeum, Tetrahymena thermophila, Enterobacteria phage RB49 and bacteriophage Felix 01 HNH endonucleases. HNH endonucleases are homing endonucleases that move extensively via lateral gene transfer [
]. This entry represents the AP2/ERF domain superfamily.
Pseudouridine synthases catalyse the isomerisation of uridine to pseudouridine (Psi) in a variety of RNA molecules, and may function as RNA chaperones. Pseudouridine is the most abundant modified nucleotide found in all cellular RNAs. There are four distinct families of pseudouridine synthases that share no global sequence similarity, but which do share the same fold of their catalytic domain(s) and uracil-binding site and are descended from a common molecular ancestor. The catalytic domain consists of two subdomains, each of which has an α+β structure that has some similarity to the ferredoxin-like fold (note: some pseudouridine synthases contain additional domains). The active site is the most conserved structural region of the superfamily and is located between the two homologous domains. These families are [
,
]:Pseudouridine synthase I, TruA.Pseudouridine synthase II, TruB, which contains and additional C-terminal PUA domain.Pseudouridine synthase RsuA. RluB, RluE and RluF are also part of this family.Pseudouridine synthase RluA. TruC, RluC and RluD belong to this family.Pseudouridine synthase TruD, which has a natural circular permutation in the catalytic domain, as well as an insertion of a family-specific α+β subdomain.TruB is responsible for the pseudouridine residue present in the T loops of virtually all tRNAs. TruB recognises the preformed 3-D structure of the T loop primarily through shape complementarity. It accesses its substrate uridyl residue by flipping out the nucleotide and disrupts the tertiary structure of tRNA [
].This model is built on a seed alignment of bacterial proteins only. Saccharomyces cerevisiae protein YNL292w (Pus4) has been shown to be the pseudouridine 55 synthase of both cytosolic and mitochondrial compartments, active at no other position on tRNA and the only enzyme active at that position in the species. A distinct yeast protein YLR175w, (centromere/microtubule-binding protein CBF5) is an rRNA pseudouridine synthase, and the archaeal set is much more similar to CBF5 than to Pus4. It is unclear whether the archaeal proteins found by this model are tRNA pseudouridine 55 synthases like TruB, rRNA pseudouridine synthases like CBF5, or (as suggested by the absence of paralogs in the Archaea) both. CBF5 likely has additional, eukaryotic-specific functions.
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. The two sequences in the alignment seed 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. This cas protein family is unique to the Pging (Porphyromonas gingivalis) subtype, but shows some sequence similarity to genes of the Cas5 type (see
).
Two lysine biosynthesis pathways evolved separately in organisms, the diaminopimelic acid (DAP) and aminoadipic acid (AAA) pathways. The DAP pathway synthesizes L-lysine from aspartate and pyruvate, and diaminopimelic acid is an intermediate. This pathway is utilised by most bacteria, some archaea, some fungi, some algae, and plants. The AAA pathway synthesizes L-lysine from alpha-ketoglutarate and acetyl coenzyme A (acetyl-CoA), and alpha-aminoadipic acid is an intermediate. This pathway is utilised by most fungi, some algae, the bacterium Thermus thermophilus, and probably some archaea, such as Sulfolobus, Thermoproteus, and Pyrococcus. No organism is known to possess both pathways [
].There four known variations of the DAP pathway in bacteria: the succinylase, acetylase, aminotransferase, and dehydrogenase pathways. These pathways share the steps converting L-aspartate to L-2,3,4,5- tetrahydrodipicolinate (THDPA), but the subsequent steps leading to the production of meso-diaminopimelate, the immediate precursor of L-lysine, are different [
].The succinylase pathway acylates THDPA with succinyl-CoA to generate N-succinyl-LL-2-amino-6-ketopimelate and forms meso-DAP by subsequent transamination, desuccinylation, and epimerization. This pathway is utilised by proteobacteria and many firmicutes and actinobacteria. The acetylase pathway is analogous to the succinylase pathway but uses N-acetyl intermediates. This pathway is limited to certain Bacillus species, in which the corresponding genes have not been identified. The aminotransferase pathway converts THDPA directly to LL-DAP by diaminopimelate aminotransferase (DapL) without acylation. This pathway is shared by cyanobacteria, Chlamydia, the archaeon Methanothermobacter thermautotrophicus, and the plant Arabidopsis thaliana. The dehydrogenase pathway forms meso-DAP directly from THDPA, NADPH, and NH4 _ by using diaminopimelate dehydrogenase (Ddh). This pathway is utilised by some Bacillus and Brevibacterium species and Corynebacterium glutamicum. Most bacteria use only one of the four variants, although certain bacteria, such as C. glutamicum and Bacillus macerans, possess both the succinylase and dehydrogenase pathways.The four sequences which make up the seed for this model are not closely related, although they are all members of the
family of aminotransferases and are more closely related to each other than to anything else. Additionally, all of them are found in the vicinity of genes involved in the biosynthesis of lysine via the diaminopimelate pathway (
), although this amounts to a separation of 12 genes in the case of Sulfurihydrogenibium azorense Az-Fu1. None of these genomes contain another strong candidate for this role in the pathway. Note: the detailed information included in the
record includes the assertions that the enzyme uses the pyridoxal pyrophosphate cofactor, which is consistent with the
family, and the assertion that the amino group donor is L-glutamate, which is undetermined for the sequences in this clade.
Peptidase family A1, also known as the pepsin family, contains peptidases with bilobed structures [
,
]. The two domains most probably evolved from the duplication of an ancestral gene encoding a primordial domain []. The active site is formed from an aspartic acid residue from each domain. Each aspartic acid occurs within a motif with the sequence D(T/S)G(T/S). Exceptionally, in the histoaspactic peptidase from Plasmodium falciparum, one of the Asp residues is replaced by His [
]. A third essential residue, Tyr or Phe, is found on the N-terminal domain only in a β-hairpin loop known as the "flap"; this residue is important for substrate binding, and most members of the family have a preference for a hydrophobic residue in the S1 substrate binding pocket. Most members of the family are active at acidic pH, but renin is unusually active at neutral pH. Family A1 peptidases are found predominantly in eukaryotes (but examples are known from bacteria [
,
]). Currently known eukaryotic aspartyl peptidases and homologues include the following:Vertebrate gastric pepsins A (
), gastricsin (
, also known pepsin C), chymosin (
; formerly known as rennin), and cathepsin E (
). Pepsin A is widely used in protein sequencing because of its limited and predictable specificity. Chymosin is used to clot milk for cheese making.
Lysosomal cathepsin D (
).
Renin (
) which functions in control of blood pressure by generating angiotensin I from angiotensinogen in the plasma.
Memapsins 1 (
; also known as BACE 2) and 2 (
; also known as BACE) are membrane-bound and are able to perform one of the two cleavages (the beta-cleavage, hence they are also known as beta-secretases) in the beta-amyloid precursor to release the the amyloid-beta peptide, which accumulates in the plaques of Alzheimer's disease patients.
Fungal peptidases such as aspergillopepsin A (
), candidapepsin (
), mucorpepsin (
; also known as
Mucorrennin), endothiapepsin (
), polyporopepsin (
), and rhizopuspepsin (
) are secreted for sapprophytic protein digestion.
Fungal saccharopepsin (
) (proteinase A) (gene PEP4) is implicated in post-translational regulation of vacuolar hydrolases.
Yeast barrierpepsin (
) (gene BAR1); a protease that cleaves alpha-factor and thus acts as an antagonist of the mating pheromone.
Fission yeast Sxa1 may be involved in degrading or processing the mating pheromones [
].In plants, phytepsin (
) degrades seed storage proteins and nepenthesin (EC 3.4.23.12) from a pitcher plant digests insect proteins. Also are included Aspartic proteinase 36 and Aspartic proteinase 39, which contribute to pollen and ovule development and have an important role in plant development in Arabidopsis [
].Plasmepsins (
and
) from Plasmodium species are important for the degradation of host haemoglobin.
Non-peptidase homologues where one or more active site residues have been replaced, include mammalian pregnancy-associated glycoproteins, an allergen from a cockroach, and a xylanase inhibitor [
].
