MXD1, also known as MAD, binds Max to form a repressive transcription factor. It antagonizes MYC transcriptional activity by competing for MAX []. It has also been shown to regulate rRNA synthesis [].
MAX gene-associated protein (MGA) is a dual-specificity transcription factor, acting as a repressor or an activator and binding to 5'-AATTTCACACCTAGGTGTGAAATT-3'. MGA regulates genes targeted by MYC-MAX, suppressing transcriptional activation by MYC and inhibiting MYC-dependent cell transformation. MGA binds DNA via a T-Box []. MGA is a component of the MLL1 complex [].
Protein max is a transcription regulator that forms a complex with MYC or MAD []. The MYC:MAX complex is a transcriptional activator, whereas the MAD:MAX complex is a repressor. MAX is also a component of the E2F6.com-1 []and MLL1 complexes []. Mutations in the MAX gene are associated with hereditary pheochromocytoma, which is a tumour of the chromaffin tissue of the adrenal medulla or sympathetic paraganglia resulting in hypertension [].This entry also includes Mxl-1 and Mxl-3 from Caenorhabditis elegans. Mxl-1 forms complexes with Mdl1. The Mdl-1:Mxl-1 complex functions in both the insulin signaling and dietary restriction pathways and is involved in the control of lifespan in response to dietary restriction []. Mxl-3 is a transcription factor that modulates the inhibition of lipolysis. It also regulates lipid metabolism during nutritional excess [].
These vegatative storage proteins are close relatives of the plant acid phosphatases () and are limited to members of the Phaseoleae including Glycine max (Soybean) and Phaseolus vulgaris (Kidney bean). These proteins are highly expressed in the leaves of repeatedly depodded plants [, ]. Vegetative storage protein (VSP) differs most strikingly from the acid phosphatases in the lack of the conserved nucleophilic aspartate residue in the N terminus, thus, they should be inactive as phosphatases. This issue was confused by the publication in 1992 of an article claiming activity for the G. max VSP. In 1994 this assertion was refuted by the separation of the activity from the VSP [].
This domain can be found in the MAX gene-associated protein (Mga), which is a dual-specificity transcription factor that contains both a bHLHZip domain and a T-box domain and is able to bind to and regulate transcriptional targets through both E-box sites as well as T-box-binding elements (TBEs) []. MAX gene-associated protein (MGA) is a dual-specificity transcription factor, acting as a repressor or an activator and binding to 5'-AATTTCACACCTAGGTGTGAAATT-3'. MGA regulates genes targeted by MYC-MAX, suppressing transcriptional activation by MYC and inhibiting MYC-dependent cell transformation. MGA binds DNA via a T-Box []. MGA is a component of the MLL1 complex [].
Mlx is a Max-like basic-helix-loop-helix zipper protein that interacts with the Max network of transcription factors [, , ]. Mlx forms a complex with MondoA (also known as MLXIP), and this complex regulates glucose-induced gene expression []. The transcriptional activity of the MondoA-Mlx complex is limited by mTOR-MondoA interaction [].
GH3 protein was first isolated from Glycine max (soybean) as an early auxin-responsive gene [, ]. Later, several plant GH3 family proteins have been identified and classified into three groups: group I proteins synthesise JA-amino acid conjugates [], group II proteins produce indole-3-acetic acid (IAA) conjugates [], group III protein are involved in the conjugation of amino acids to 4-substituted benzoate []. This entry also includes proteins from bacteria, fungi and animals.
Sin3a is a transcriptional repressor and a homologue of the SIN3 repressor from yeast. Sin3a associates with the strong repressive isoform of Mxi1, a helix-loop-helix leucone zipper that associates with Max to antagonize Myc oncogenic activities []. Unlike Mxi1 and Myc, expression of Sin3a does not vary during development []. Sin3a is a component of several complexes, including the REST-CoREST repressor complex [], the PER complex which maintains circadian rhythm []and the Sin3 HDAC complex []. Sin3a also interacts with FOXK1 to regulate cell cycle progression []. Sin3a has three PAH domains by which it interacts with HCFC1, REST and SAP30 [, ].
This entry represents a group acetyltransferases, including NSI from Arabidopsis, SNAT1/2 from rice and Histone acetyltransferase TAP1/2 from Glycine max (Soybean). NSI is a vascular-expressed acetyltransferase that interacts with NSP, which is a nuclear shuttle protein []. It has been shown to regulate the nuclear export of the viral genome and potentially other non transcriptional nuclear events in plant cells []. SNAT1 catalyses the N-acetylation of serotonin into N-acetylserotonin, the penultimate step in the synthesis of melatonin [, , , ]. TAP1 acts as a susceptibility factor that is hijacked by Avh52 in order to promote acetylation of histones H2A and H3 during early infection by Phytophtora sojae [].This entry also includes predicted N-acetyltransferases from bacteria.
This family consists of Rhizobium NolX and Xanthomonas HrpF proteins. The interaction between the plant pathogen Xanthomonas campestris pv. vesicatoria (strain 85-10) and its host plants is controlled by hrp genes (hypersensitive reaction and pathogenicity), which encode a type III protein secretion system. Among type III-secreted proteins are avirulence proteins, effectors involved in the induction of plant defence reactions. HrpF is dispensable for protein secretion but required for AvrBs3 recognition in planta, is thought to function as a translocator of effector proteins into the host cell []. NolX, a Glycine max (Soybean) cultivar specificity protein, is secreted by a type III secretion system (TTSS) and shows homology to HrpF. It is not known whether NolX functions at the bacterium-plant interface or acts inside the host cell. NolX is expressed in planta only during the early stages of nodule development [].
This entry represents aldo-keto reductase family 4A/B. This is a group of plant aldo-keto reductases, including NAD(P)H-dependent 6'-deoxychalcone synthase from Glycine max (Soybean) [], Deoxymugineic acid synthase 1 from Zea mays [], and NADPH-dependent codeinone reductase from Papaver somniferum (Opium poppy). Codeinone reductase catalyses the NADPH-dependent reduction of codeinone to codeine [].In general, the aldo-keto reductase (AKR) protein superfamily members reduce carbonyl substrates such as: sugar aldehydes, keto-steroids, keto-prostaglandins, retinals, quinones, and lipid peroxidation by-products [, ]. However, there are some exceptions, such as the reduction of steroid double bonds catalysed by AKR1D enzymes (5beta-reductases); and the oxidation of proximate carcinogen trans-dihydrodiol polycyclic aromatic hydrocarbons; while the beta-subunits of potassium gated ion channels (AKR6 family) control Kv channel opening [].Structurally, they contain an (alpha/beta)8-barrel motif, display large loops at the back of the barrel which govern substrate specificity, and have a conserved cofactor binding domain. The binding site is located in a large, deep, elliptical pocket in the C-terminal end of the beta sheet, the substrate being bound in an extended conformation. The hydrophobic nature of the pocket favours aromatic and apolar substrates over highly polar ones []. They catalyse an ordered bi bi kinetic mechanism in which NAD(P)H cofactor binds first and leaves last []. Binding of the NADPH coenzyme causes a massive conformational change, reorienting a loop, effectively locking the coenzyme in place. This binding is more similar to FAD- than to NAD(P)-binding oxidoreductases [].
The following small plant proteins are evolutionary related:Gamma-thionins from Triticum aestivum (Wheat) endosperm (gamma-purothionins) and gamma-hordothionins from Hordeum vulgare(Barley) are toxic to animal cells and inhibit protein synthesis in cell free systems [].A flower-specific thionin (FST) from Nicotiana tabacum (Common Tobacco)[].Antifungal proteins (AFP) from the seeds of Brassicaceae species such as radish, mustard, turnip and Arabidopsis thaliana (Thale Cress)[].Inhibitors of insect alpha-amylases from sorghum [].Probable protease inhibitor P322 from Solanum tuberosum (Potato).A germination-related protein from Vigna unguiculata (Cowpea) [].Anther-specific protein SF18 from sunflower. SF18 is a protein that contains a gamma-thionin domain at its N terminus and a proline-rich C-terminal domain.Glycine max (Soybean) sulphur-rich protein SE60 [].Vicia faba (Broad bean) antibacterial peptides fabatin-1 and -2.In their mature form, these proteins generally consist of about 45 to 50 amino-acid residues. As shown in the following schematic representation, these peptides contain eight conserved cysteines involved in disulphide bonds.+-------------------------------------------+| +-------------------+ || | | |xxCxxxxxxxxxxCxxxxxCxxxCxxxxxxxxxCxxxxxxCxCxxxC| | | |+---|----------------+ |+------------------+'C': conserved cysteine involved in a disulphide bond.The folded structure of Gamma-purothionin is characterised by a well-defined 3-stranded anti-parallel β-sheet and a short α-helix []. Three disulphide bridges are located in the hydrophobic core between the helix and sheet, forming a cysteine-stabilised α-helical motif. This structure differs from that of the plant alpha- and beta- thionins, but is analogous to scorpion toxins and insect defensins.
This entry represents a family of acid phosphatase [, ]from plants which are closely related to the class B non-specific acid phosphatase OlpA (, which is believed to be a 5'-nucleotide phosphatase) and somewhat more distantly to another class B phosphatase, AphA (). Together these three clades define a subfamily of Acid phosphatase (Class B), which corresponds to the IIIB subfamily of the haloacid dehalogenase (HAD) superfamily of aspartate nucleophile hydrolases. It has been reported that the best substrates were purine 5'-nucleoside phosphates []. This is in concordance with the assignment of the Haemophilus influenzae hel protein (from ) as a 5'-nucleotidase, however there is presently no other evidence to support this specific function for this family of plant phosphatases. Many genes from this family have been annotated as vegetative storage proteins (VSPs) due to their close homology with these earlier-characterised gene products which are highly expressed in leaves. There are significant differences however, including expression levels and distribution []. The most important difference is the lack in authentic VSPs of the nucleophilic aspartate residue, which is instead replaced by serine, glycine or asparagine. Thus these proteins can not be expected to be active phosphatases. This issue was confused by the publication in 1992 of an article claiming activity for the Glycine max (Soybean) VSP []. In 1994 this assertion was refuted by the separation of the activity from the VSP. This entry explicitly excludes the VSPs which lack the nucleophilic aspartate. The possibility exists, however, that some members of this family may, while containing all of the conserved HAD-superfamily catalytic residues, lack activity and have a function related to the function of the VSPs rather than the acid phosphatases.
A number of eukaryotic proteins, which probably are sequence specific DNA-binding proteins that act as transcription factors, share a conserved domain of 40 to 50 amino acid residues. It has been proposed []that this domain is formed of two amphipathic helices joined by a variable length linker region that could form a loop. This 'helix-loop-helix' (HLH) domain mediates protein dimerization and has been found in the proteins listed below []. Most of these proteins have an extra basic region of about 15 amino acid residues that is adjacent to the HLH domain and specifically binds to DNA. They are referred as basic helix-loop-helix proteins (bHLH), and are classified in two groups: class A (ubiquitous) and class B (tissue-specific). Members of the bHLH family bind variations on the core sequence 'CANNTG', also referred to asthe E-box motif. The homo- or heterodimerization mediated by the HLH domain is independent of, but necessary for DNA binding, as two basic regions are required for DNA binding activity. The HLH proteins lacking the basic domain (Emc, Id) function as negative regulators, since they form heterodimers, but fail to bind DNA. The hairy-related proteins (hairy, E(spl), deadpan) also repress transcription although they can bind DNA. The proteins of this subfamily act together with co-repressor proteins, like groucho, through their -terminal motif WRPW.Proteins containing a HLH domain include:The myc family of cellular oncogenes [], which is currently known to contain four members: c-myc, N-myc, L-myc, and B-myc. The myc genes are thought to play a role in cellular differentiation and proliferation.Proteins involved in myogenesis (the induction of muscle cells). In mammals MyoD1 (Myf-3), myogenin (Myf-4), Myf-5, and Myf-6 (Mrf4 or herculin), in birds CMD1 (QMF-1), in Xenopus MyoD and MF25, in Caenorhabditis elegans CeMyoD, and in Drosophila nautilus (nau).Vertebrate proteins that bind specific DNA sequences ('E boxes') in various immunoglobulin chains enhancers: E2A or ITF-1 (E12/pan-2 and E47/pan-1), ITF-2 (tcf4), TFE3, and TFEB.Vertebrate neurogenic differentiation factor 1 that acts as differentiation factor during neurogenesis.Vertebrate MAX protein, a transcription regulator that forms a sequence- specific DNA-binding protein complex with myc or mad.Vertebrate Max Interacting Protein 1 (MXI1 protein) which acts as a transcriptional repressor and may antagonize myc transcriptional activity by competing for max.Proteins of the bHLH/PAS superfamily which are transcriptional activators. In mammals, AH receptor nuclear translocator (ARNT), single-minded homologues (SIM1 and SIM2), hypoxia-inducible factor 1 alpha (HIF1A), AH receptor (AHR), neuronal pas domain proteins (NPAS1 and NPAS2), endothelial pas domain protein 1 (EPAS1), mouse ARNT2, and human BMAL1. In Drosophila, single-minded (SIM), AH receptor nuclear translocator (ARNT), trachealess protein (TRH), and similar protein (SIMA).Mammalian transcription factors HES, which repress transcription by acting on two types of DNA sequences, the E box and the N box.Mammalian MAD protein (max dimerizer) which acts as transcriptional repressor and may antagonize myc transcriptional activity by competing for max.Mammalian Upstream Stimulatory Factor 1 and 2 (USF1 and USF2), which bind to a symmetrical DNA sequence that is found in a variety of viral and cellular promoters.Human lyl-1 protein; which is involved, by chromosomal translocation, in T- cell leukemia.Human transcription factor AP-4.Mouse helix-loop-helix proteins MATH-1 and MATH-2 which activate E box- dependent transcription in collaboration with E47.Mammalian stem cell protein (SCL) (also known as tal1), a protein which may play an important role in hemopoietic differentiation. SCL is involved, by chromosomal translocation, in stem-cell leukemia.Mammalian proteins Id1 to Id4 []. Id (inhibitor of DNA binding) proteins lack a basic DNA-binding domain but are able to form heterodimers with other HLH proteins, thereby inhibiting binding to DNA.Drosophila extra-macrochaetae (emc) protein, which participates in sensory organ patterning by antagonizing the neurogenic activity of the achaete- scute complex. Emc is the homologue of mammalian Id proteins.Human Sterol Regulatory Element Binding Protein 1 (SREBP-1), a transcriptional activator that binds to the sterol regulatory element 1 (SRE-1) found in the flanking region of the LDLR gene and in other genes.Drosophila achaete-scute (AS-C) complex proteins T3 (l'sc), T4 (scute), T5 (achaete) and T8 (asense). The AS-C proteins are involved in the determination of the neuronal precursors in the peripheral nervous system and the central nervous system.Mammalian homologues of achaete-scute proteins, the MASH-1 and MASH-2 proteins.Drosophila atonal protein (ato) which is involved in neurogenesis.
