The Css1/CcsB/ResB family of proteins are found in bacteria and chloroplasts. They are essential for the biogenesis of c-type cytochromes, apparently being required at the step of heme attachment [
,
,
].
A group of microtubule-associated proteins called +TIPs (plus end tracking
proteins), including EB1 (end-binding protein 1) family proteins, labelgrowing microtubules ends specifically in diverse organisms and are implicated
in spindle dynamics, chromosome segregation, and directing microtubules towardcortical sites. EB1 members have a bipartite composition: the N-terminal CHdomain (
) mediates microtubule plus end localization and a C-terminal cargo binding domain (EB1-C) that captures cell polarity
determinants. The EB1-C domain comprises a unique EB1-like sequence motif thatacts as a binding site for other +TIP proteins. It interacts with the carboxy
terminus of the adenomatous polyposis coli (APC) tumor suppressor, a wellconserved +TIP phosphoprotein with a pivotal function in cell cycle
regulation. Another binding partner of the EB1-C domain is the well conserved+TIP protein dynactin, a component of the large cytoplasmic dynein/dynactin
complex [,
,
].The ~80-residue EB1-C domain starts with a long smoothly curved helix
(alpha1), which is followed by a hairpin connection leading to a short secondhelix (alpha2) running antiparallel to alpha1. The two
parallel alpha1 helices of the EB1-C domain dimer wrap around each other in aslightly left-handed supercoil. The two alpha2 helices run antiparallel to
helices alpha1 and form a similar fork in the opposite orientation and rotatedby 90 degrees. As a result, two helical segments from each monomer form a four-helix
bundle. The side chain forming the hydrophobic core of this bundle are highlyconserved [
,
,
].Some protein known to contain an EB1-C domain are listed below:
Yeast protein BIM1.Fission yeast microtubule integrity protein mal3.Vertebrate microtubule-associated protein RP/EB family member 1 (EB1).Vertebrate microtubule-associated protein RP/EB family member 2 (EB2 or
RP1).Vertebrate microtubule-associated protein RP/EB family member 3 (EBF3).
This entry represents the microtubule-associated protein RP/EB (MAPRE) family, including MAPRE1 (EB1), MAPRE2 (RP1, also known as EB2), MAPRE3 (EBF3, also known as EB3) and their homologues from eukaryotes. Despite their high protein sequence conservation, the individual EBs exhibit different regulatory and functional properties [
]. For instance, EB1 and EB3, but not EB2, promote persistent microtubule growth by suppressing catastrophes [].EB1 contains an N-terminal calponin homology (CH) domain that is responsible for the interaction with microtubules (MTs), and a C-terminal coiled coil domain that extends into a four-helix bundle, required for dimer formation [
]. Through their C-terminal sequences, EBs interact with most other known +TIPs (plus end tracking proteins) and recruit many of them to the growing MT ends [,
]. EB1 is involved in MT anchoring at the centrosome and cell migration []. EB2 is highly expressed in pancreatic cancer cells, and seems to be involved in perineural invasion [
]. EB3 is specifically upregulated upon myogenic differentiation. Knockdown of EB3, but not that of EB1, prevents myoblast elongation and fusion into myotubes [
]. This entry also includes bZIP transcription factor hapX from the yeast
Neosartorya fumigata, which is a transcription factor required for repression of genes during iron starvation [
].
This short domain is rich in cysteines and histidines. The pattern of conservation is similar to that found in DAG_PE-bind (
), therefore we have termed this domain DC1 for divergent C1 domain. This domain probably also binds to two zinc ions. The function of proteins with this domain is uncertain, however this domain may bind to molecules such as diacylglycerol. This family are found in plant proteins.
Globins are haem-containing proteins involved in binding and/or transporting oxygen. They belong to a very large and well studied family that is widely distributed in many organisms [
]. Globins have evolved from a common ancestor and can be divided into three groups: single-domain globins, and two types of chimeric globins, flavohaemoglobins and globin-coupled sensors. Bacteria have all three types of globins, while archaea lack flavohaemoglobins, and eukaryotes lack globin-coupled sensors []. Several functionally different haemoglobins can coexist in the same species. The major types of globins include:Haemoglobin (Hb): tetramer of two alpha and two beta chains, although embryonic and foetal forms can substitute the alpha or beta chain for ones with higher oxygen affinity, such as gamma, delta, epsilon or zeta chains. Hb transports oxygen from lungs to other tissues in vertebrates [
]. Hb proteins are also present in unicellular organisms where they act as enzymes or sensors [].Myoglobin (Mb): monomeric protein responsible for oxygen storage in vertebrate muscle [
].Neuroglobin: a myoglobin-like haemprotein expressed in vertebrate brain and retina, where it is involved in neuroprotection from damage due to hypoxia or ischemia [
]. Neuroglobin belongs to a branch of the globin family that diverged early in evolution. Cytoglobin: an oxygen sensor expressed in multiple tissues. Related to neuroglobin [
].Erythrocruorin: highly cooperative extracellular respiratory proteins found in annelids and arthropods that are assembled from as many as 180 subunit into hexagonal bilayers [
].Leghaemoglobin (legHb or symbiotic Hb): occurs in the root nodules of leguminous plants, where it facilitates the diffusion of oxygen to symbiotic bacteriods in order to promote nitrogen fixation.Non-symbiotic haemoglobin (NsHb): occurs in non-leguminous plants, and can be over-expressed in stressed plants [
].Flavohaemoglobins (FHb): chimeric, with an N-terminal globin domain and a C-terminal ferredoxin reductase-like NAD/FAD-binding domain. FHb provides protection against nitric oxide via its C-terminal domain, which transfers electrons to haem in the globin [
].Globin-coupled sensors: chimeric, with an N-terminal myoglobin-like domain and a C-terminal domain that resembles the cytoplasmic signalling domain of bacterial chemoreceptors. They bind oxygen, and act to initiate an aerotactic response or regulate gene expression [
,
]. Protoglobin: a single domain globin found in archaea that is related to the N-terminal domain of globin-coupled sensors [
].Truncated 2/2 globin: lack the first helix, giving them a 2-over-2 instead of the canonical 3-over-3 α-helical sandwich fold. Can be divided into three main groups (I, II and II) based on structural features [
].Leghaemoglobins are haem-proteins, first identified in root nodules of leguminous plants, where they are crucial for supplying sufficient oxygen to root nodule bacteria for nitrogen fixation to occur [,
]. Although leghaemoglobin and myoglobin both share a common fold, and both regulate the facilitated diffusion of oxygen, leghemoglobins regulate oxygen affinity through a mechanism different from that of myoglobin using a novel combination of haem pocket amino acids that lower the oxygen affinity [,
]. The structure of leghaemoglobins is similar to that of haemoglobins and myoglobins, although there is little sequence conservation []. The protein is largely α-helical, eight helices providing the scaffold for a well-defined haem-binding pocket []. By contrast with the tetrameric mammalian globin assembly, the plant form is monomeric []. The structural similarity of leghaemoglobins and haemoglobins has suggested a common evolutionary origin. It was thought that haemoglobins may be found in plants other than legumes [
], and indeed globins have now been identified in the roots of non-leguminous plants, where they have a role in respiratory metabolism in the root cells []. This entry also represents Non-symbiotic haemoglobins (NsHb) which play important roles in a variety of cellular processes. A class I NsHb from cotton plants can be induced in plant roots as a defence mechanism against pathogen invasions, possibly by modulating nitric oxide (NO) levels [
]. Several NsHbs appear to play a role NO scavenging in plants, indicating that the primordial function of haemoglobins may well be to protect against nitrosative stress and to modulate NO signalling functions [].
The cytochrome b6f integral membrane protein complex transfers electrons
between the two reaction centre complexes of oxygenic photosynthetic membranes, and participates in formation of the transmembrane
electrochemical proton gradient by also transferring protons from the stromal to the internal lumen compartment. The cytochrome b6f complex
contains four polypeptides: cytochrome f (285 aa); cytochrome b6 (215 aa); Rieske iron-sulphur protein (179 aa); and subunit IV (160 aa) [
]. In its structure and functions, the cytochrome b6f complex bears extensive analogy
to the cytochrome bc1 complex of mitochondria and photosynthetic purple bacteria; cytochrome f (cyt f) plays a role analogous to that of cytochrome
c1, in spite of their different structures []. The 3D structure of Brassica rapa (Turnip) cyt f has been determined [
]. The lumen-side segment of cyt f includes two structural domains: a small one above a
larger one that, in turn, is on top of the attachment to the membrane domain. The large domain consists of an anti-parallel β-sandwich and a
short haem-binding peptide, which form a three-layer structure. The small domain is inserted between β-strands F and G of the large domain and is
an all-beta domain. The haem nestles between two short helices at the N terminus of cyt f. Within the second helix is the sequence motif for the
c-type cytochromes, CxxCH (residues 21-25), which is covalently attached tothe haem through thioether bonds to Cys-21 and Cys-24. His-25 is the fifth
haem iron ligand. The sixth haem iron ligand is the alpha-amino group of Tyr-1 in the first helix [
]. Cyt f has an internal network of water molecules that may function as a proton wire [
]. The water chain appearsto be a conserved feature of cyt f.
This entry represents the large domain of cytochrome f.
The cytochrome b6f integral membrane protein complex transfers electrons
between the two reaction centre complexes of oxygenic photosynthetic membranes, and participates in formation of the transmembrane
electrochemical proton gradient by also transferring protons from the stromal to the internal lumen compartment. The cytochrome b6f complex
contains four polypeptides: cytochrome f (285 aa); cytochrome b6 (215 aa); Rieske iron-sulphur protein (179 aa); and subunit IV (160 aa) [
]. In its structure and functions, the cytochrome b6f complex bears extensive analogy
to the cytochrome bc1 complex of mitochondria and photosynthetic purple bacteria; cytochrome f (cyt f) plays a role analogous to that of cytochrome
c1, in spite of their different structures [].
Nucleolar GTP-binding protein 1, Rossman-fold domain
Type:
Domain
Description:
This domain represents a conserved region of approximately 60 residues in length within nucleolar GTP-binding protein 1 (NOG1). The NOG1 family includes eukaryotic, bacterial and archaeal proteins. In Saccharomyces cerevisiae, the NOG1 gene has been shown to be essential for cell viability, suggesting that NOG1 may play an important role in nucleolar functions. In particular, NOG1 is believed to be functionally linked to ribosome biogenesis, which occurs in the nucleolus. In eukaryotes, NOG1 mutants were found to disrupt the biogenesis of the 60S ribosomal subunit [].The DRG and OBG proteins as well as the prokaryotic NOG-like proteins are homologous throughout their length to the amino half of eukaryotic NOG1, which contains the GTP binding motifs (
); the N-terminal GTP-binding motif is required for function.
Protein tyrosine (pTyr) phosphorylation is a common post-translational modification which can create novel recognition motifs for protein interactions and cellular localisation, affect protein stability, and regulate enzyme activity. Consequently, maintaining an appropriate level of protein tyrosine phosphorylation is essential for many cellular functions. Tyrosine-specific protein phosphatases (PTPase;
) catalyse the removal of a phosphate group attached to a tyrosine residue, using a cysteinyl-phosphate enzyme intermediate. These enzymes are key regulatory components in signal transduction pathways (such as the MAP kinase pathway) and cell cycle control, and are important in the control of cell growth, proliferation, differentiation and transformation [
,
]. The PTP superfamily can be divided into four subfamilies []:(1) pTyr-specific phosphatases(2) dual specificity phosphatases (dTyr and dSer/dThr)(3) Cdc25 phosphatases (dTyr and/or dThr)(4) LMW (low molecular weight) phosphatasesBased on their cellular localisation, PTPases are also classified as:Receptor-like, which are transmembrane receptors that contain PTPase domains [
]
Non-receptor (intracellular) PTPases [
]
All PTPases carry the highly conserved active site motif C(X)5R (PTP signature motif), employ a common catalytic mechanism, and share a similar core structure made of a central parallel β-sheet with flanking α-helices containing a β-loop-α-loop that encompasses the PTP signature motif [
]. Functional diversity between PTPases is endowed by regulatory domains and subunits. This family includes the mammalian protein tyrosine phosphatase-like protein, PTPLA. A significant variation of PTPLA from other protein tyrosine phosphatases is the presence of proline instead of catalytic arginine at the active site. It is thought that PTPLA proteins have a role in the development, differentiation, and maintenance of a number of tissue types [
].
The Kunitz-type soybean trypsin inhibitor (STI) family consists mainly of proteinase inhibitors from Leguminosae seeds [
]. They belong to MEROPS inhibitor family I3, clan IC. They exhibit proteinase inhibitory activity against serine proteinases; trypsin (MEROPS peptidase family S1, ) and subtilisin (MEROPS peptidase family S8,
), thiol proteinases (MEROPS peptidase family C1,
) and aspartic proteinases (MEROPS peptidase family A1,
) [
]. Inhibitors from cereals are active against subtilisin and endogenous alpha-amylases, while some also inhibit tissue plasminogen activator. The inhibitors are usually specific for either trypsin or chymotrypsin, and some are effective against both. They are thought to protect the seeds against consumption by animal predators, while at the same time existing as seed storage proteins themselves - all the actively inhibitory members contain 2 disulphide bridges. The existence of a member with no inhibitory activity, winged bean albumin 1, suggests that the inhibitors may have evolved from seed storage proteins.Proteins from the Kunitz family contain from 170 to 200 amino acid residues and one or two intra-chain disulphide bonds. The best conserved region is found in their N-terminal section. The crystal structures of soybean trypsin inhibitor (STI), trypsin inhibitor DE-3 from the Kaffir tree Erythrina caffra (ETI) [
] and the bifunctional proteinase K/alpha-amylase inhibitor from wheat (PK13) have been solved, showing them to share the same 12-stranded β-sheet structure as those of interleukin-1 and heparin-binding growth factors []. The β-sheets are arranged in 3 similar lobes around a central axis, 6 strands forming an anti-parallel β-barrel. Despite the structural similarity, STI shows no interleukin-1 bioactivity, presumably as a result of their primary sequence disparities. The active inhibitory site containing the scissile bond is located in the loop between β-strands 4 and 5 in STI and ETI.The STIs belong to a superfamily that also contains the interleukin-1
proteins, heparin binding growth factors (HBGF) and histactophilin, all of which have very similar structures, but share no sequence similarity with
the STI family.
The Kunitz-type soybean trypsin inhibitor (STI) family consists mainly of proteinase inhibitors from Leguminosae seeds [
]. They belong to MEROPS inhibitor family I3, clan IC. They exhibit proteinase inhibitory activity against serine proteinases; trypsin (MEROPS peptidase family S1, ) and subtilisin (MEROPS peptidase family S8,
), thiol proteinases (MEROPS peptidase family C1,
) and aspartic proteinases (MEROPS peptidase family A1,
) [
]. STI has a beta-Trefoil type fold consisting of a closed barrel and a hairpin triplet, with internal pseudo threefold symmetry.The C-terminal domain of Clostridium spp. neurotoxins have an overfold that is very similar to that of the Kunitz STI family. The tetanus toxin binds to the gangliosides receptor, GT1b, and is composed of light and heavy chains, where the light chain is responsible for toxicity; the Kunitz-like domain is found on the C-terminal of the heavy chain, and is responsible for binding to sensitive cells [
].
The ubiquitin fold modifier 1 (Ufm1) is the most recently discovered ubiquitin-like modifier whose conjugation (ufmylation) system is conserved in multicellular organisms. Ufm1 is known to covalently attach with cellular protein(s) via a specific E1-activating enzyme (Uba5), an E2-conjugating enzyme (Ufc1), and a E3-ligating enzyme [
]. This entry represents E3 UFM1-protein ligase 1 (Ufl1) which mediates the covalent attachment of the ubiquitin-like modifier UFM1 to lysine residues on target proteins and plays a key role in reticulophagy (also called ER-phagy) induced in response to endoplasmic reticulum stress [,
,
,
,
].
RNA polymerases catalyse the DNA dependent polymerisation of RNA. Prokaryotes contain a single RNA polymerase compared to three in eukaryotes (not including mitochondrial and chloroplast polymerases). This entry, domain 4, represents the funnel domain. The funnel domain contains the binding site for some elongation factors [
,
].
Phosphopantetheine (or pantetheine 4' phosphate) is the prosthetic group of acyl carrier proteins (ACP) in some multienzyme complexes where it serves as a 'swinging arm' for the attachment of activated fatty acid and amino-acid groups [
].The amino-terminal region of the ACP proteins is well defined and consists of four α helices arranged in a right-handed bundle held together by interhelical hydrophobic interactions. The Asp-Ser-Leu (DSL) motif is conserved in all of the ACP sequences, and the 4'-PP prosthetic group is covalently linked via a phosphodiester bond to the serine residue. The DSL sequence is present at the amino terminus of helix II, a domain of the protein referred to as the recognition helix and which is responsible for the interaction of ACPs with the enzymes of type II fatty acid synthesis [
].This entry represents the phosphopantetheine-binding domain from polyketide synthases. Polyketide synthases are large multidomain proteins involved in the synthesis of secondary metabolites [
].
This domain is typically between 142 to 163 amino acids in length is found at the C terminus of activator complex subunit 4 (gene name PSME4, PA2000 or BLM10), a component of the 19S cap complex of the eukaryotic 26S proteasome. The tertiary structure of BLM10 from
Saccharomyces cerevisiaehas been solved, showing that the C terminus is important for helping to form the BLM10 cap that covers the entry pore of the proteasome, restricting access for potential substrates. The C-terminal residues bind in the pocket between proteasome subunits alpha5 and alpha6, in a similar site to where the C-termini of the ATPases of the 19S proteasomal cap also bind [
].
Malic enzymes (malate oxidoreductases) catalyse the oxidative decarboxylation of malate to form pyruvate, a reaction important in a number of metabolic pathways - e.g. carbon dioxide released from the reaction may be used in sugar production during the Calvin cycle of photosynthesis [
]. There are 3 forms of the enzyme []: an NAD-dependent form that decarboxylates oxaloacetate; an NAD-dependent form that does not decarboxylate oxalo-acetate; and an NADPH-dependent form []. Other proteins known to be similar to malic enzymes are the Escherichia coli scfA protein; an enzyme from Zea mays (Maize), formerly thought to be cinnamyl-alcohol dehydrogenase []; and the hypothetical Saccharomyces cerevisiae protein YKL029c.Studies on the duck liver malic enzyme reveals that it can be alkylated by bromopyruvate, resulting in the loss of oxidative decarboxylation and the subsequent enhancement of pyruvate reductase activity [
]. The alkylated form is able to bind NADPH but not L-malate, indicating impaired substrate or divalent metal ion-binding in the active site []. Sequence analysis has highlighted a cysteine residue as the point of alkylation, suggesting that it may play an important role in the activity of the enzyme [], although it is absent in the sequences from some species.Malic enzyme is a tetramer comprised of subunits with four domains each [
,
,
].This entry represents the N-terminal domain of the NAD(P)-dependent malic enzyme and related proteins from bacteria, eukaryotes and archaea.
Malic enzymes (malate oxidoreductases) catalyse the oxidative decarboxylation of malate to form pyruvate, a reaction important in a number of metabolic pathways - e.g. carbon dioxide released from the reaction may be used in sugar production during the Calvin cycle of photosynthesis [
]. There are 3 forms of the enzyme []: an NAD-dependent form that decarboxylates oxaloacetate; an NAD-dependent form that does not decarboxylate oxalo-acetate; and an NADPH-dependent form []. Other proteins known to be similar to malic enzymes are the Escherichia coli scfA protein; an enzyme from Zea mays (Maize), formerly thought to be cinnamyl-alcohol dehydrogenase []; and the hypothetical Saccharomyces cerevisiae protein YKL029c.Studies on the duck liver malic enzyme reveals that it can be alkylated by bromopyruvate, resulting in the loss of oxidative decarboxylation and the subsequent enhancement of pyruvate reductase activity [
]. The alkylated form is able to bind NADPH but not L-malate, indicating impaired substrate-or divalent metal ion-binding in the active site []. Sequence analysis has highlighted a cysteine residue as the point of alkylation, suggesting that it may play an important role in the activity of the enzyme [], although it isabsent in the sequences from some species.
There are three well conserved regions in the enzyme sequences. Two of them seem to be involved in the binding NAD or NADP. This entry represents the third domain, located in the central part of the enzymes, its function is not yet known.
Members of this family are predicted to be bifunctional enzymes. Their C-terminal domain belongs to the GHMP kinase domain superfamily. Based on sequence similarity, it is predicted to be galactokinases (a subgroup of GHMP kinases).GHMP kinases are a unique class of ATP-dependent enzymes (the abbreviation of which refers to the original members: galactokinase, homoserine kinase, mevalonate kinase, and phosphomevalonate kinase) [
]. Enzymes belonging to this superfamily contain three well-conserved motifs, the second of which has the typical sequence Pro-X-X-X-Gly-Leu-X-Ser-Ser-Ala and is involved in ATP binding []. The phosphate binding loop in GHMP kinases is distinct from the classical P-loops found in many ATP/GTP binding proteins. The bound ADP molecule adopts a rare syn conformation and is in the opposite orientation from those bound to the P-loop-containing proteins []. GHMP kinases display a distinctly bilobal appearance with their N-terminal subdomains dominated by a mixed β-sheet flanked on one side by α-helices and their C-terminal subdomains containing a four stranded anti-parallel β-sheet [,
,
,
].The domain in the N-terminal region belongs to the UDP-glycosyltransferase/glycogen phosphorylase SCOP domain superfamily (as detected by SMART), and to the glycosyltransferase family according to PSI-BLAST analysis. The exact function of this particular variety of this domain is unknown.
This entry represents an N-terminal conserved domain found in all galactokinases, irrespective of how many other ATP binding sites, etc that they carry [
]. The function of this domain appears to be to bind galactose [], and it is normally located at the N terminus of these enzymes []. It is associated with and
. While all enzymes in this entry posses galactokinase activity, some are annotated as N-acetylgalactosamine kinases as they also posses this enzyme activity.
This domain can also be found in mevalonate kinase and related proteins from all domains of life. It can also be found in arabinose kinase from Arabidopsis [
].
The RbcX protein has been identified as having a chaperonin-like function as it assists in the correct assembly of RbcL and RbcS subunits during RuBisCO biogenesis and it is also required to reach its maximal activity [
,
]. The rbcX gene is juxtaposed to and cotranscribed with rbcL and rbcS encoding RubisCO in Anabaena sp. (strain CA / ATCC 33047) []. Crystal structure studies revealed that RbcX is composed almost exclusively of α-helices, which form an unusual four-helix bundle. Additionally, all known RbcX proteins exist as homodimers (RbcX2). The central cleft of this homodimer binds the C-terminal of a RbcL monomer, stabilizing it, and the peripheral region of RbcX2 binds a second RbcL monomer, which allows the RbcL homodimers to be in the correct orientation [].
This family represents a group of neutral/alkaline ceramidases found in both bacteria and eukaryotes [
,
,
]. They hydrolyse the sphingolipid ceramide into sphingosine and free fatty acid.
The essential RNA helicase Mtr4 is an exosome-activating cofactor. This arch domain can be found in Mtr4 and Ski2 (the cytosolic homologue of Mtr4). The arch domain is required for proper 5.8S rRNA processing, and appears to function independently of canonical helicase activity [
].
The sterile alpha motif (SAM) domain is a protein interaction module present in a wide variety of proteins [
,
] involved in many biological processes. The SAM domain that spreads over around 70 residues and one of the most common protein modules found in eukaryotic genomes []. SAM domains have been shown to form homo- and hetero-oligomers, forming multiple self-association architectures and also binding to various non-SAM domain-containing proteins [], nevertheless with a low affinity constant [
]. SAM domains also appear to possess the ability to bind RNA []. Smaug, a protein that helps to establish a morphogen gradient in Drosophila embryos by repressing the translation of nanos (nos) mRNA, binds to the 3' untranslated region (UTR) of nos mRNA via two similar hairpin structures. The 3D crystal structure of the Smaug RNA-binding region shows a cluster of positively charged residues on the Smaug-SAM domain, which could be the RNA-binding surface. This electropositive potential is unique among all previously determined SAM-domain structures and is conserved among Smaug-SAM homologues. These results suggest that the SAM domain might have a primary role in RNA binding.Structural analyses show that the SAM domain is arranged in a small five-helix bundle with two large interfaces [
]. In the case of the SAM domain of EphB2, each of these interfaces is able to form dimers. The presence of these two distinct intermonomers binding surface suggest that SAM could form extended polymeric structures [].
The biosynthesis of disaccharides, oligosaccharides and polysaccharides involves the action of hundreds of different glycosyltransferases. These enzymes catalyse the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, forming glycosidic bonds. A classification of glycosyltransferases using nucleotide diphospho-sugar, nucleotide monophospho-sugar and sugar phosphates ([intenz:2.4.1.-]) and related proteins into distinct sequence based families has been described []. This classification is available on the CAZy (CArbohydrate-Active EnZymes) web site. The same three-dimensional fold is expected to occur within each of the families. Because 3-D structures are better conserved than sequences, several of the families defined on the basis of sequence similarities may have similar 3-D structures and therefore form 'clans'.Proteins in this entry are glycosyltransferases with phosphorylase activities. Members use phosphate to break alpha 1,4 linkages between pairs of glucose residues at the end of long glucose polymers, releasing alpha-D-glucose 1-phosphate. The nomenclature convention is to preface the name according to the natural substrate, as in glycogen phosphorylase, starch phosphorylase, maltodextrin phosphorylase, etc.The main role of glycogen phosphorylase (GPase) is to provide phosphorylated glucose molecules (G-1-P) [
]. GPase is a highly regulated allosteric enzyme. The net effect of the regulatory site allows the enzyme to operate at a variety of rates; the enzyme is not simply regulated as "on"or "off", but rather it can be thought of being set to operate at an ideal rate based on changing conditions at in the cell. The most important allosteric effector is the phosphate molecule covalently attached to Ser14. This switches GPase from the b (inactive) state to the a (active) state. Upon phosphorylation, GPase attains about 80% of its Vmax. When the enzyme is not phosphorylated, GPase activity is practically non-existent at low AMP levels.
There is some apparent controversy as to the structure of GPase. All sources agree that the enzyme is multimeric, but there is apparent controversy as to the enzyme being a tetramer or a dimer. Apparently, GPase (in the a
form) forms tetramers in the crystal form. The consensus seems to be that `regardless of the a or b form, GPase functions as a dimer in vivo[
]. The GPase monomer is best described as consisting of two domains, an N-terminal domain and a C-terminal domain []. The C-terminal domain is often referred to as the catalytic domain. It consists of a β-sheet core surrounded by layers of helical segments [
]. The vitamin cofactor pyridoxal phosphate (PLP) is covalently attached to the amino acid backbone. The N-terminal domain also consists of a central β-sheet core and is surrounded by layers of helical segments. The N-terminal domain contains different allosteric effector sites to regulate the enzyme.Bacterial phosphorylases follow the same catalytic mechanisms as their plant and animal counterparts, but differ considerably in terms of their substrate specificity and regulation. The catalytic domains are highly conserved while the regulatory sites are only poorly conserved. For maltodextrin phosphorylase from Escherichia coli the physiological role of the enzyme in the utilisation of maltidextrins is known in detail; that of all the other bacterial phosphorylases is still unclear. Roles in regulatuon of endogenous glycogen metabolism in periods of starvation, and sporulation, stress response or quick adaptation to changing environments are possible [
].
Photosystem I (PSI) [
] is an integral membrane protein complex that uses light energy to mediate electron transfer from plastocyanin to ferredoxin. PSI is found in the chloroplast of plants and cyanobacteria. The electron transfer components of the reaction centre of PSI are a primary electron donor P-700 (chlorophyll dimer) and five electron acceptors: A0 (chlorophyll), A1 (a phylloquinone) and three 4Fe-4S iron-sulphur centres: Fx, Fa, and Fb.PsaA and psaB, two closely related proteins, are involved in the binding of P700, A0, A1, and Fx. psaA and psaB are both integral membrane proteins of 730 to 750 amino acids that seem to contain 11 transmembrane segments. The Fx 4Fe-4S iron-sulphur centre is bound by four cysteines; two of these cysteines are provided by the psaA protein and the two others by psaB. The two cysteines in both proteins are proximal and located in a loop between the ninth and tenth transmembrane segments. A leucine zipper motif seems to be present [
] downstream of the cysteines and could contribute to dimerisation of psaA/psaB.
Cdc6 (also known as Cell division cycle 6 or Cdc18) functions as a regulator at the early stages of DNA replication, by helping to recruit and load the Minichromosome Maintenance Complex (MCM) onto DNA and may have additional roles in the control of mitotic entry. Precise duplication of chromosomal DNA is required for genomic stability during replication. Cdc6 has an essential role in DNA replication and irregular expression of Cdc6 may lead to genomic instability. Cdc6 over-expression is observed in many cancerous lesions. DNA replication begins when an origin recognition complex (ORC) binds to a replication origin site on the chromatin. Studies indicate that Cdc6 interacts with ORC through the Orc1 subunit, and that this association increases the specificity of the ORC-origins interaction. Further studies suggest that hydrolysis of Cdc6-bound ATP promotes the association of the replication licensing factor Cdt1 with origins through an interaction with Orc6 and this in turn promotes the loading of MCM2-7 helicase onto chromatin. The MCM2-7 complex promotes the unwinding of DNA origins, and the binding of additional factors to initiate the DNA replication. S-Cdk (S-phase cyclin and cyclin-dependent kinase complex) prevents rereplication by causing the Cdc6 protein to dissociate from ORC and prevents the Cdc6 and MCM proteins from reassembling at any origin. By phosphorylating Cdc6, S-Cdk also triggers Cdc6's ubiquitination. The Cdc6 protein is composed of three domains, an N-terminal AAA+ domain with Walker A and B, and Sensor-1 and -2 motifs. The central region contains a conserved nucleotide binding/ATPase domain and is a member of the ATPase superfamily. [
,
,
,
,
].The C-terminal domain of cell division control protein 6 (CDC6) assumes a winged helix fold, with a five α-helical bundle (α15-α19) structure, backed on one side by three beta strands (β6-β8). It has been shown that this domain acts as a DNA-localisation factor, however its exact function is, as yet, unknown. Putative functions include: (1) mediation of protein-protein interactions and (2) regulation of nucleotide binding and hydrolysis. Mutagenesis studies have shown that this domain is essential for appropriate CDC6 activity [
].
This group represents the cell division control protein Cdc6 and Cdc18, which are essential initiation factors for DNA replication [
].Cdc6 appears to have an important and perhaps unique dual role in S phase, it is first required for the initiation of DNA replication and then actively participates in the suppression of nuclear division. It interacts with the origin recognition complex (ORC). It targeted for degradation by the E3 ubiquitin ligase complex SCF (Cdc4) [
,
].Cdc18 is part of the checkpoint control that prevents mitosis from occurring until S phase is completed. It plays a key role in coupling S phase to start and mitosis. It acts at the initiation of DNA replication and plays a major role in controlling the onset of S-phase. Together with orp1, it is involved in the maintenance of replication forks and activation of cds1-dependent S-phase checkpoint [
,
,
,
,
].
This entry represents a group of haemoglobin-like proteins found in eubacteria, cyanobacteria, protozoa, algae and plants, but not in animals or yeast. These proteins have a truncated 2-over-2 rather than the canonical 3-over-3 α-helical sandwich fold []. They include:HbN (or GlbN): a truncated haemoglobin-like protein that binds oxygen cooperatively with a very high affinity and a slow dissociation rate, which may exclude it from oxygen transport. It appears to be involved in bacterial nitric oxide detoxification and in nitrosative stress [
].Cyanoglobin (or GlbN): a truncated haemoprotein found in cyanobacteria that has high oxygen affinity, and which appears to serve as part of a terminal oxidase, rather than as a respiratory pigment [
].HbO (or GlbO): a truncated haemoglobin-like protein with a lower oxygen affinity than HbN. HbO associates with the bacterial cell membrane, where it significantly increases oxygen uptake over membranes lacking this protein. HbO appears to interact with a terminal oxidase, and could participate in an oxygen/electron-transfer process that facilitates oxygen transfer during aerobic metabolism [
].Glb3: a nuclear-encoded truncated haemoglobin from plants that appears more closely related to HbO than HbN. Glb3 from Arabidopsis thaliana (Mouse-ear cress) exhibits an unusual concentration-independent binding of oxygen and carbon dioxide [
].
This family consists of several bacterial lipopolysaccharide core biosynthesis proteins (WaaY or RfaY). The waaY, waaQ, and waaP genes are located in the central operon of the waa (formerly rfa) locus on the chromosome of Escherichia coli. This locus contains genes whose products are involved in the assembly of the core region of the lipopolysaccharide molecule. WaaY is the enzyme that phosphorylates HepII in this system [
].
Basic leucine-zipper (bZIP) proteins are found in eukaryotes. They are typically between 174 and 411 amino acids in length. Various bZIP proteins have been found and shown to play a role in seed-specific gene expression. bZIP binds to the alpha-globulin gene promoter, but not to promoters of other major storage genes such as glutelin, prolamin and albumin [
]. This entry represents a C-terminal domain found in bZIP proteins. It is found in association with
. There is a conserved KVK sequence motif and a single completely conserved residue K that may be functionally important.
This group of metallopeptidases belong to the MEROPS peptidase family M1 (clan MA(E)), the type example being aminopeptidase N from Homo sapiens (Human). The protein fold of the peptidase domain for members of this family resembles that of thermolysin, the type example for clan MA.Membrane alanine aminopeptidase ()
is part of the HEXXH+E
group; it consists entirely of aminopeptidases, spread across a widevariety of species [
]. Functional studies show that CD13/APN catalyzes the removal of single amino acids from the amino terminus of small peptides and probably plays a role in their final digestion; one family member (leukotriene-A4 hydrolase) is known to hydrolyse the epoxide leukotriene-A4to form an inflammatory mediator [
]. This hydrolase has been shown tohave aminopeptidase activity [
], and the zinc ligands of the M1 familywere identified by site-directed mutagenesis on this enzyme [
] CD13 participates in trimming peptides bound to MHC class II molecules [] and cleaves MIP-1 chemokine, which alters target cell specificity from basophils to eosinophils []. CD13 acts as a receptor for specific strains of RNA viruses (coronaviruses) which cause a relatively large percentage of upper respiratory tract infections.
The 3-dehydroquinate synthase (DHQS) domain can exist in isolation or as a domain in the pentafunctional AROM polypeptide (
) [
]. 3-dehydroquinate synthase catalyses the formation of dehydroquinate (DHQ) and orthophosphate from 3-deoxy-D-arabino heptulosonic 7 phosphate []. This reaction is part of the shikimate pathway which is involved in the biosynthesis of aromatic amino acids.
This entry represents vacuolar protein sorting-associated protein 35 (Vps35) from eukaryotes.
Vps35 is a core component of the retromer complex which functions in the endosome-to-Golgi retrieval cargo transport pathway [
,
]. Vps35 is part of the a cargo-selective complex trimer (CSC) of the retromer, which is composed of Vps26, Vps29 and Vps35 and is responsible for binding to and sorting protein cargo []. Mutations in the Vps35 gene have been linked to Parkinson's disease [
]. Structurally, VPS35 forms a horseshoe-shaped, right-handed, α-helical solenoid [].
TrmO (also known as TsaA or YaeB) is a RNA methyltransferase responsible for N6-methylation of N6-threonylcarbamoyladenosine in tRNAs. It has a unique single-sheeted β-barrel structure and represent a new category of AdoMet-dependent methyltransferases [
].The following uncharacterised proteins have been shown to be evolutionary related and to contain a TrmO-like beta barrel structural domain domain:Agrobacterium tumefaciens Ti plasmid protein virR.Pseudomonas aeruginosa protein rcsF.Archaeoglobus fulgidus hypothetical protein AF0241.Archaeoglobus fulgidus hypothetical protein AF0433.Methanococcus jannaschii hypothetical protein MJ1583.Methanobacterium thermoautotrophicum hypothetical protein MTH1797.Mammalian Nef-associated protein 1 (NAP1). The crystal structure of Haemophilus influenzae TrmO has been solved. In addition to the N-terminal β-barrel methyltransferase domain it has a C-terminal domain containing the conserved sequence motif DPRxxY [
].
Thymidine kinase (TK) (
) is an ubiquitous enzyme that catalyzes the ATP-dependent phosphorylation of thymidine.
Two different families of thymidine kinase have been identified [
,
] and are represented in this entry; one groups together thymidine kinase from herpesviruses, as well as cytosolic thymidylate kinases and the second family groups thymidine kinase from various sources that include, vertebrates, bacteria, the bacteriophage T4, poxviruses, African swine fever virus (ASFV) and fish lymphocystis disease virus (FLDV). The major capsid protein of insect iridescent viruses also belongs to this family.
Thymidine kinase (TK) (
) is an ubiquitous enzyme that catalyzes the ATP-dependent phosphorylation of thymidine.
Two different families of thymidine kinase have been identified [
,
] and are represented in this entry; one groups together thymidine kinase from herpesviruses, as well as cytosolic thymidylate kinases and the second family groups thymidine kinase from various sources that include, vertebrates, bacteria, the bacteriophage T4, poxviruses, African swine fever virus (ASFV) and fish lymphocystis disease virus (FLDV). The major capsid protein of insect iridescent viruses also belongs to this family.This entry represents a conserved site of thymidine kinase.
The bifunctional nuclease (BFN) domain is specific to bacteria and plant
organisms. It has both RNase and DNase activities [].The dimer of the BFN domain forms a wedge, each monomer being a basic
triangular shape. The BFN domain is composed of an eight-stranded, distortedβ-sheet consisting of a four-stranded, antiparallel β-sheet (B1, B2, B3,
B8), and a four-stranded mixed β-sheet (B4, B5, B6, B7). The sheets areintercalated by three short α-helices (H1, H3, H4), while a longer α-helix (H2) forms the central core of the dimer interface [
].Some proteins known to contain a BFN domain are listed below:Thermotoga maritima TM0160, a conserved hypothetical protein. Plant bifunctional nuclease in basal defense response (BBD) proteins,
regulators in abscisic acid (ABA)-mediated defense responses.This entry represents the BFN domain.
RNA polymerases catalyse the DNA dependent polymerisation of RNA. Prokaryotes contain a single RNA polymerase compared to three in eukaryotes (not including mitochondrial and chloroplast polymerases). This domain, domain 7, represents a mobile module of the RNA polymerase. Domain 7 interacts with the lobe domain of Rpb2 (
) [
,
].
RNA polymerases catalyse the DNA dependent polymerisation of RNA. Prokaryotes contain a single RNA polymerase compared to three in eukaryotes (not including mitochondrial and chloroplast polymerases). This domain, domain 6, represents a mobile module of the RNA polymerase. Domain 6 forms part of the shelf module [
,
]. This family appears to be specific to the largest subunit of RNA polymerase II.
This entry represents the plant phospholipase D (PLD), a calcium-dependent enzyme that hydrolyses glycerol-phospholipids at the terminal phosphodiesteric bond. Arabidopsis PLD has been implicated in plant response to macronutrient availability [
]. PLD alpha 1 from Setaria italica (foxtail millet) has been linked to drought tolerance [].
This entry represents a group of transcriptional adaptors, including transcriptional adapter 2 (TADA2) from animals and plants, and Ada2 from yeasts.Ada2 is a component of the SAGA/ADA coactivator complex, which regulates numerous cellular processes by coordinating histone acetylation [
,
]. There are two Drosophila Ada2 homologues, dAda2a and dAda2b. dAda2b is a component of Spt-Ada-Gcn5-acetyltransferase (SAGA) complexes, while dAda2a associates with dGcn5 but is not incorporated into dSAGA-type complexes [
]. Mammalian TADA2 is a component of the ATAC complex, a complex with histone acetyltransferase activity on histones H3 and H4. The ATAC complex is involved in mammalian development, histone acetylation, cell cycle progression, and prevention of apoptosis during embryogenesis [
].
Aconitase A/isopropylmalate dehydratase small subunit, swivel domain
Type:
Domain
Description:
Aconitase (aconitate hydratase;
) is an iron-sulphur protein that contains a [4Fe-4S]-cluster and catalyses the interconversion of isocitrate and citrate via a cis-aconitate intermediate. Aconitase functions in both the TCA and glyoxylate cycles, however unlike the majority of iron-sulphur proteins that function as electron carriers, the [4Fe-4S]-cluster of aconitase reacts directly with an enzyme substrate. In eukaryotes there is a cytosolic form (cAcn) and a mitochondrial form (mAcn) of the enzyme. In bacteria there are also 2 forms, aconitase A (AcnA) and B (AcnB). Several aconitases are known to be multi-functional enzymes with a second non-catalytic, but essential function that arises when the cellular environment changes, such as when iron levels drop [
,
]. Eukaryotic cAcn and mAcn, and bacterial AcnA have the same domain organisation, consisting of three N-terminal alpha/beta/alpha domains, a linker region, followed by a C-terminal 'swivel' domain with a beta/beta/alpha structure (1-2-3-linker-4), although mAcn is small than cAcn. However, bacterial AcnB has a different organisation: it contains an N-terminal HEAT-like domain, followed by the 'swivel' domain, then the three alpha/beta/alpha domains (HEAT-4-1-2-3) [].This entry represents the 'swivel' domain found at the C-terminal of eukaryotic mAcn, cAcn/IPR1 and IRP2, and bacterial AcnA. This domain has a three layer beta/beta/alpha structure, and in cytosolic Acn is known to rotate between the cAcn and IRP1 forms of the enzyme. This domain is also found in the small subunit of isopropylmalate dehydratase (LeuD).3-isopropylmalate dehydratase (or isopropylmalate isomerase; IPMI;
) catalyses the stereo-specific isomerisation of 2-isopropylmalate and 3-isopropylmalate, via the formation of 2-isopropylmaleate. This enzyme performs the second step in the biosynthesis of leucine, and is present in most prokaryotes and many fungal species. The prokaryotic enzyme is a heterodimer composed of a large (LeuC) and small (LeuD) subunit, while the fungal form is a monomeric enzyme. Both forms of isopropylmalate are related and are part of the larger aconitase family [
].
Aconitase (aconitate hydratase) [
] is the enzyme from the tricarboxylic acid cycle that catalyzes the reversible isomerization of citrate and isocitrate. Cis-aconitate is formed as an intermediary product during the course of the reaction. In eukaryotes two isozymes of aconitase are known to exist: one found in the mitochondrial matrix and the other found in the cytoplasm. Aconitase, in its active form, contains a 4Fe-4S iron-sulphur cluster; three cysteine residues have been shown to be ligands of the 4Fe-4S cluster. It has been shown that the aconitase family also contains the following proteins: Iron-responsive element binding protein (IRE-BP). IRE-BP is a cytosolic protein that binds to iron-responsive elements (IREs). IREs are stem-loop structures found in the 5'UTR of ferritin, and delta aminolevulinic acid synthase mRNAs, and in the 3'UTR of transferrin receptor mRNA. 3-isopropylmalate dehydratase (
) (isopropylmalate isomerase), the enzyme that catalyzes the second step in the biosynthesis of leucine.
Homoaconitase (
) (homoaconitate hydratase), an enzyme that participates in the alpha-aminoadipate pathway of lysine biosynthesis and that converts cis-homoaconitate into homoisocitric acid.
Esherichia coli protein YbhJ. The signatures in this entry, identify the cysteine residues involved in the binding of the 4Fe-4S iron-sulphur cluster.
This domain is found in tRNA methyltransferases including tRNA (guanine-N(1)-)-methyltransferases (TRMD) and mitochondrial ribonuclease P protein 1. Proteins containing this domain also include tRNA (guanine(9)-N1)-methyltransferase (Trm10) from yeasts. Escherichia coli K12 tRNA (guanine-N(1)-)-methyltransferase catalyses the conversion of a guanosine residue to N1-methylguanine in position 37, next to the anticodon, in tRNA [
]. Mitochondrial RNase P (mtRNase P) functions in mitochondrial tRNA maturation [].
This entry represents a domain found in class IV SAM-dependent methyltransferases TRM10-type [
]. Methyltransferases classified as class IV (SPOUT) are homodimers and methylate only RNA. The common core of the SPOUT fold contains a five-stranded beta sheet, flanked by two layers of alpha helices. The core can be divided into two subdomains, both displaying an alpha/beta architecture: (1) the N-terminal strands exhibit a Rossmanoidal alpha/beta fold while (2) an important part of the C-terminal (~ 30 residues) is tucked back into the structure forming a conserved topological trefoil knot where SAM binding occurs. The active site, located at the interface of the two subunits, isformed by amino acids from both monomers [,
].TRM10-type methyltransferases include tRNA (guanine(9)-N(1))-methyltransferase, tRNA (adenine(9)-N(1))-methyltransferase and RNA (guanine-9-)-methyltransferase domain-containing protein. TRM10 homologues are widely found in eukaryotes and archaea, but not in bacteria.
In transfer RNA many different modified nucleosides are found, especially in the anticodon region.
tRNA (guanine-N1-)-methyltransferase is one of several nucleases operating together with the tRNA-modifying enzymes before the formation of the mature tRNA. It catalyses the reaction:
S-adenosyl-L-methionine + tRNA ->S-adenosyl-L-homocysteine + tRNA containing
N1-methylguanine methylating guanosine(G) to N1-methylguanine (1-methylguanosine (m1G)) at position 37 of tRNAs that read CUN (leucine), CCN(proline), and CGG (arginine) codons. The presence of m1G improves the cellular growth rate and the polypeptide steptime and also prevents the tRNA from shifting the reading frame []. The mechanism of the trmD3-induced frameshift involving mutant tRNA(Pro) and tRNA(Leu) species has been investigated []. It has been suggested that the conformation of the anticodon loop may be a major determining element for the formation of m1G37 in vivo [].
O-Glycosyl hydrolases (
) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families [
,
]. This classification is available on the CAZy (CArbohydrate-Active EnZymes) website.Glycoside hydrolase family 38
comprises enzymes with only one known activity; alpha-mannosidase (
) (
).
Lysosomal alpha-mannosidase is necessary for the catabolism of N-linked carbohydrates released during glycoprotein turnover. The enzyme catalyses the hydrolysis of terminal, non-reducing alpha-D-mannose residues in alpha-D-mannosides, and can cleave all known types of alpha-mannosidic linkages. Defects in the gene cause lysosomal alpha-mannosidosis (AM), a lysosomal storage disease characterised by the accumulation of unbranched oligo-saccharide chains.This entry represents the N-terminal domain of the glycoside hydrolase 38 family protein.
O-Glycosyl hydrolases (
) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families [
,
]. This classification is available on the CAZy (CArbohydrate-Active EnZymes) website.Glycoside hydrolase family 38
comprises enzymes with only one known activity; alpha-mannosidase (
) (
). This domain is found at the C terminus of glycosyl hydrolases from family 38.
This superfamily represents a structural domain found in glycoside hydrolase families 38 (
, e.g. alpha-mannosidase) [
] and 57 (, e.g. 4-alpha-glucanotransferase, N-terminal) [
], as well as in NodB-like polysaccharide deacetylase and in some hypothetical proteins (e.g. TT1467, N-terminal domain). This domain consists of a 7-stranded β/α barrel, although in some families the β-barrels may be distorted and may vary in the number of strands.
This entry represents a domain found in members of the glycosyl hydrolases families 38. This domain is found in the central region that adopts a structure consisting of three alpha helices, in an immunoglobulin/albumin-binding domain-like fold. The domain is predominantly found in the enzyme alpha-mannosidase [
]. Glycoside hydrolase family 38
comprises enzymes with only one known activity; alpha-mannosidase (
) (
).
Lysosomal alpha-mannosidase is necessary for the catabolism of N-linked carbohydrates released during glycoprotein turnover. The enzyme catalyses the hydrolysis of terminal, non-reducing alpha-D-mannose residues in alpha-D-mannosides, and can cleave all known types of alpha-mannosidic linkages. Defects in the gene cause lysosomal alpha-mannosidosis (AM), a lysosomal storage disease characterised by the accumulation of unbranched oligo-saccharide chains.
This superfamily represents a structural domain found in glycoside hydrolase families 38 (
, e.g. alpha-mannosidase) [
].O-Glycosyl hydrolases (
) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families [
,
]. This classification is available on the CAZy (CArbohydrate-Active EnZymes) website.Glycoside hydrolase family 38
comprises enzymes with only one known activity; alpha-mannosidase (
) (
).
Lysosomal alpha-mannosidase is necessary for the catabolism of N-linked carbohydrates released during glycoprotein turnover. The enzyme catalyses the hydrolysis of terminal, non-reducing alpha-D-mannose residues in alpha-D-mannosides, and can cleave all known types of alpha-mannosidic linkages. Defects in the gene cause lysosomal alpha-mannosidosis (AM), a lysosomal storage disease characterised by the accumulation of unbranched oligo-saccharide chains.
The 26S proteasome is composed of a core protease, known as the 20S proteasome, capped at one or both ends by the 19S regulatory complex (RC). The RC is composed of at least 18 different subunits in two subcomplexes, the base and the lid, which form the portions proximal and distal to the 20S proteolytic core, respectively [
].This family consists of the RC subunit S5A or non-ATPase regulatory subunit 4 (PSMD4, also known as Rpn10). Rpn10 binds and presumably selects ubiquitin-conjugates for destruction [
,
].
This is the AAA ATPase domain found at the C-terminal of plant senescence-associated proteins and spartin. In Hemerocallis, petals have a genetically based program that leads to senescence and cell death approximately 24 hours, after the flower opens, and it is believed that senescence proteins produced around that time have a role in this program [
]. This domain is also found at the C-terminal of Spartin, a protein from higher vertebrates associated with endosomal trafficking and microtubule dynamics []. Spartin functions presynaptically with endocytic adaptor Eps15 to regulate synaptic growth and function. Mutations in human spartin gene cause Troyer syndrome, a hereditary spastic paraplegia []. This AAA ATPase domain similar to other AAA proteins contain an α/β nucleotide-binding domain (NBD) and a smaller four-helix bundle domain (HBD) []. Uniquely among AAA structures, spastin has two helices (N-terminal α1 and C-terminal α11) that embrace the NBD [].
This is a family of nucleoporins conserved from yeast to human.Nup85 Nucleoporin is an essential component of the nuclear pore complex (NPC) that seems to be required for NPC assembly and maintenance. As part of the NPC Nup107-160 subcomplex plays a role in RNA export and in tethering NUP98/Nup98 and NUP153 to the nucleus. The Nup107-160 complex seems to be required for spindle assembly during mitosis. NUP85 is required for membrane clustering of CCL2-activated CCR2. Seems to be involved in CCR2-mediated chemotaxis of monocytes and may link activated CCR2 to the phosphatidyl-inositol-3-kinase-Rac-lammellipodium protrusion cascade [
,
,
]. The Nup84 complex is composed of one copy each of Nup84, Nup85, Nup120, Nup133, Nup145C, Sec13, and Seh1. The structure of a complex of Nup85 and Seh1 was solved [
]. The N terminus of Nup85 is inserted and forms a three-stranded blade that completes the Seh1 6-bladed β-propeller in trans. Following its N-terminal insertion blade, Nup85 forms a compact cuboid structure composed of 20 helices, with two distinct modules, referred to as crown and trunk [].
This family represents Respirasome Complex Assembly Factor 1 (RCAF1) a Rab5-interacting protein involved in the assembly of mitochondrial respiratory complexes [
].
Transcription factor IIA (TFIIA) is one of several factors that form part of a transcription pre-initiation complex along with RNA polymerase II, the TATA-box-binding protein (TBP) and TBP-associated factors, on the TATA-box sequence upstream of the initiation start site. After initiation, some components of the pre-initiation complex (including TFIIA) remain attached and re-initiate a subsequent round of transcription. TFIIA binds to TBP to stabilise TBP binding to the TATA element. TFIIA also inhibits the cytokine HMGB1 (high mobility group 1 protein) binding to TBP [
], and can dissociate HMGB1 already bound to TBP/TATA-box.Human and Drosophila TFIIA have three subunits: two large subunits, LN/alpha and LC/beta, derived from the same gene, and a small subunit, S/gamma. Yeast TFIIA has two subunits: a large TOA1 subunit that shows sequence similarity to the N-terminal of LN/alpha and the C-terminal of LC/beta, and a small subunit, TOA2 that is highly homologous with S/gamma. The conserved regions of the large and small subunits of TFIIA combine to form two domains: a four-helix bundle (helical domain) composed of two helices from each of the N-terminal regions of TOA1 and TOA2 in yeast; and a β-barrel (β-barrel domain) composed of β-sheets from the C-terminal regions of TOA1 and TOA2 [
].This superfamily represents the α-helical domain found at the N-terminal of the gamma subunit of transcription factor TFIIA.
Transcription factor IIA (TFIIA) is one of several factors that form part of a transcription pre-initiation complex along with RNA polymerase II, the TATA-box-binding protein (TBP) and TBP-associated factors, on the TATA-box sequence upstream of the initiation start site. After initiation, some components of the pre-initiation complex (including TFIIA) remain attached and re-initiate a subsequent round of transcription. TFIIA binds to TBP to stabilise TBP binding to the TATA element. TFIIA also inhibits the cytokine HMGB1 (high mobility group 1 protein) binding to TBP [], and can dissociate HMGB1 already bound to TBP/TATA-box.Human and Drosophila TFIIA have three subunits: two large subunits, LN/alpha and LC/beta, derived from the same gene, and a small subunit, S/gamma. Yeast TFIIA has two subunits: a large TOA1 subunit that shows sequence similarity to the N-terminal of LN/alpha and the C-terminal of LC/beta, and a small subunit, TOA2 that is highly homologous with S/gamma. The conserved regions of the large and small subunits of TFIIA combine to form two domains: a four-helix bundle (helical domain) composed of two helices from each of the N-terminal regions of TOA1 and TOA2 in yeast; and a β-barrel (β-barrel domain) composed of β-sheets from the C-terminal regions of TOA1 and TOA2 [
].This entry represents the precursor that yields both the alpha and beta subunits of TFIIA. The TFIIA heterotrimer is an essential general transcription initiation factor for the expression of genes transcribed by RNA polymerase II [
].
The PWI domain, named after a highly conserved PWI tri-peptide located within its N-terminal region, is a ~80 amino acid module, which is found either at the N terminus or at the C terminus of eukaryotic proteins involved in pre-mRNA processing [
]. It is generally found in association with other domains such as RRM and RS. The PWI domain is a RNA/DNA-binding domain that has an equal preference for single- and double-stranded nucleic acids and is likely to have multiple important functions in pre-mRNA processing []. Proteins containing this domain include the SR-related nuclear matrix protein of 160kDa (SRm160) splicing and 3'-end cleavage-stimulatory factor, and the mammalian splicing factor PRP3.The PWI domain is a soluble, globular and independently folded domain which consists of a four-helix bundle, with structured N- and C-terminal elements [
].
This family consists of cytochrome b6/f complex subunit 5 (PetG). The cytochrome bf complex, found in green plants, eukaryotic algae and cyanobacteria, connects photosystem I to photosystem II in the electron transport chain, functioning as a plastoquinol:plastocyanin/cytochrome c6 oxidoreductase [
]. The purified complex from the unicellular alga Chlamydomonas reinhardtii contains seven subunits; namely four high molecular weight subunits (cytochrome f, Rieske iron-sulphur protein, cytochrome b6, and subunit IV) and three approximately miniproteins (PetG, PetL, and PetX) []. Stoichiometry measurements are consistent with every subunit being present as two copies per b6/f dimer. The absence of PetG affects either the assembly or stability of the cytochrome bf complex in C. reinhardtii [].
Oxygenic photosynthesis uses two multi-subunit photosystems (I and II) located in the cell membranes of cyanobacteria and in the thylakoid membranes of chloroplasts in plants and algae. Photosystem II (PSII) has a P680 reaction centre containing chlorophyll 'a' that uses light energy to carry out the oxidation (splitting) of water molecules, and to produce ATP via a proton pump. Photosystem I (PSI) has a P700 reaction centre containing chlorophyll that takes the electron and associated hydrogen donated from PSII to reduce NADP+ to NADPH. Both ATP and NADPH are subsequently used in the light-independent reactions to convert carbon dioxide to glucose using the hydrogen atom extracted from water by PSII, releasing oxygen as a by-product.PSII is a multisubunit protein-pigment complex containing polypeptides both intrinsic and extrinsic to the photosynthetic membrane [
,
,
]. Within the core of the complex, the chlorophyll and beta-carotene pigments are mainly bound to the antenna proteins CP43 (PsbC) and CP47 (PsbB), which pass the excitation energy on to the reaction centre proteins D1 (Qb, PsbA) and D2 (Qa, PsbD) that bind all the redox-active cofactors involved in the energy conversion process. The PSII oxygen-evolving complex (OEC) oxidises water to provide protons for use by PSI, and consists of OEE1 (PsbO), OEE2 (PsbP) and OEE3 (PsbQ). The remaining subunits in PSII are of low molecular weight (less than 10kDa), and are involved in PSII assembly, stabilisation, dimerisation, and photo-protection []. This family represents PsbZ (Ycf9), which is a core low molecular weight transmembrane protein of photosystem II in thylakoid-containing chloroplasts of cyanobacteria and plants. It is thought to be located at the interface of PSII and LHCII (light-harvesting complex II) complexes, the latter containing the light-harvesting antenna. PsbZ appears to act as a structural factor, or linker, that stabilises the PSII-LHCII supercomplexes, which fail to form in PsbZ-deficient mutants. This may in part be due to the marked decrease in two LHCII antenna proteins, CP26 and CP29, found in PsbZ-deficient mutants, which result in structural changes, as well as functional modifications in PSII [
]. PsbZ may also be involved in photo-protective processes under sub-optimal growth conditions.
This domain occurs in some putative nucleic acid binding proteins. One of these proteins has been partially characterised [
] and contains two putative phosphorylation sites and a possible dimerisation / leucine zipper domain.
This family consists of the DVL family of proteins. In a gain-of-function genetic screen for genes that influence fruit development in Arabidopsis, DEVIL (DVL) gene was identified. DVL (also known as Small polypeptide ROTUNDIFOLIA) is a small protein and over expression of the protein results in pleiotropic phenotypes featured by shortened stature, rounder rosette leaves, clustered inflorescences, shortened pedicles, and siliques with pronged tips. DVL family is a novel class of small polypeptides and the overexpression phenotypes suggest that these polypeptides may have a role in plant development playing a role as negative regulators of cell proliferation [
,
,
].
The SRAP (SOS-response associated peptidase) family is characterised by the SRAP domain with a novel thiol autopeptidase activity, whose active site in human HMCES is comprised of the catalytic triad residues C2, E127, and H210 [
]. SRAP proteins are evolutionarily conserved in all domains of life. For instance, human HMCES and E. coli YedK are similar in both sequence and structure []. HMCES was originally identified as a possible reader of 5hmC in embryonic stem cell extracts using a double-stranded DNA molecule containing 5hmC as bait []. The bacterial members have operonic associations with the SOS DNA damage response, mutagenic translesion DNA polymerases, non-homologous DNA-ending-joining networks that employ Ku and an ATP-dependent ligase, and other repair systems []. Abasic (AP) sites are one of the most common DNA lesions that block replicative polymerases. SRAP proteins shield the AP site from endonucleases and error-prone polymerases [
]. Both HMCES and YedK have been found to preferentially bind ssDNA and efficiently form DNA-protein crosslinks (DPCs) to AP sites in ssDNA. They crosslink to AP sites via a stable thiazolidine DNA-protein linkage formed with the N-erminal cysteine and the aldehyde form of the AP deoxyribose []. In B Cells, HMCES has also been shown to mediate microhomology-mediated alternative-end-joining through its SRAP domain [
].
Ubiquinone biosynthesis hydroxylase, UbiH/UbiF/VisC/COQ6, conserved site
Type:
Conserved_site
Description:
This entry represents FAD-dependent hydroxylases (monooxygenases) which are all believed to act in the aerobic ubiquinone biosynthesis pathway [
]. A separate set of hydroxylases, as yet undiscovered, are believed to be active under anaerobic conditions []. In Escherichia coli, three enzyme activities have been described: UbiB (which acts first at position 6, see ), UbiH (which acts at position 4, [
]) and UbiF (which acts at position 5, []). UbiH and UbiF are similar to one another and form the basis of this subfamily. Interestingly, E. coli contains another hydroxylase gene, called visC, that is highly similar to UbiF, adjacent to UbiH and, when mutated, results in a phenotype similar to that of UbiH (which has also been named visB) []. Several other species appear to have three homologs in this family, although they assort themselves differently on phylogenetic trees (e.g. Xylella and Mesorhizobium) making it difficult to ascribe a specific activity to each one. Eukaryotes appear to have only a single homologue in this subfamily (COQ6, []) which complements UbiH, but also possess a non-orthologous gene, COQ7 which complements UbiF.This entry represents the conserved site of the ubiquinone biosynthesis hydroxylase enzyme.
This entry represents a family of FAD-dependent hydroxylases (monooxygenases), which are all believed to act in the aerobic ubiquinone biosynthesis pathway [
]. In Escherichia coli, three enzyme activities have been described: UbiI, UbiH and UbiF []. UbiH and UbiF are similar to one another and form the basis of this subfamily. UbiI (also known as visC) [] is highly similar to UbiF, adjacent to UbiH and, when mutated, results in a phenotype similar to that of UbiH (also known as visB) []. Several other species appear to have three homologues in this family, although they assort themselves differently on phylogenetic trees (e.g. Xylella and Mesorhizobium) making it difficult to ascribe a specific activity to each one. Eukaryotes appear to have only a single homologue in this subfamily (COQ6, []) which complements UbiH, but also possess a non-orthologous gene, COQ7 which complements UbiF.
One pathway for the assimilation of ammonia and glutamate biosynthesis involves glutamate synthase (
) which transfers the amide group of glutamine to 2-oxoglutarate to yield two molecules of glutamate.
2 L-glutamate + NADP
+= L-glutamine + 2-oxoglutarate + NADPH + H
+.
This describes a family in several archaeal and deeply branched bacterial lineages of a homotetrameric form of the NADPH-dependent or NADH-dependent glutamate synthase (
and
respectively) small subunit. There is no corresponding large subunit.
Domain II of the enzyme dihydroprymidine dehydrogenase binds FAD. Dihydroprymidine dehydrogenase catalyses the first and rate-limiting step of pyrimidine degradation by converting pyrimidines to the corresponding 5,6- dihydro compounds [
]. This domain carries two Fe4-S4 clusters.
The α-helical ferredoxin domain contains two Fe4-S4 clusters, typical of bacterial ferredoxin. Iron-sulphur proteins play an important role in electron transfer processes and in various enzymatic reactions. In eukaryotes, the mitochondria are the major site of Fe-S cluster biosynthesis in the cell, used for the assembly of mitochondrial and non-mitochondrial Fe-S proteins. The α-helical ferredoxin domain is present in several proteins involved in redox reactions, including the C-terminal of the respiratory proteins succinate dehydrogenase (SQR) in bacteria/mitochondria, and fumarate reductase (QFR) in bacteria. SQR is analogous to the mitochondrial respiratory complex II, and is involved in the electron transport pathway from succinate as a donor to the acceptor ubiquinone. SQR helps prevent the formation of reactive oxygen species and is used during aerobic respiration, whereas QFR does not and, consequently, is used to catalyse the final step of anaerobic respiration using the acceptor fumarate [
].The α-helical ferredoxin domain is also present in the N-terminal of the cytosolic protein dihydropyrimidine dehydrogenase, (DPD) which catalyses the NADPH-dependent, rate-limiting step in pyrimidine degradation, converting pyrimidines to 5,6-dihydro compounds [
]. DPD catalysis involves electron transfer from NADPH to the substrate via the Fe4-S4 centre and FAD. In mammals, this pathway produces the neurotransmitter beta-alanine.
Alpha-L-arabinofuranosidase B (AkAbfB) comprises two domains: a catalytic domain and an arabinose-binding domain (ABD). This entry represents the ABD domain. ABD has a β-trefoil fold similar to that of carbohydrate-binding module (CBM) family 13 but also with a number of distinctive characteristics, suggesting that it could be classified into a new CBM family [
].
Diphosphate--fructose-6-phosphate 1-phosphotransferase catalyses the addition of phosphate from diphosphate (PPi) to fructose 6-phosphate to give fructose 1,6-bisphosphate (
). The enzyme is also known as pyrophosphate-dependent phosphofructokinase. The usage of PPi-dependent enzymes in glycolysis presumably frees up ATP for other processes [
]. represents the ATP-dependent 6-phosphofructokinase enzyme contained within Phosphofructokinase. This entry contains primarily bacterial, plant alpha, and plant beta sequences. These may be dimeric nonallosteric enzymes (bacteria) or allosteric heterotetramers (plants) [
].
The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction [
,
]. These proteins differ widely in size and oligomeric state, and have limited sequence homology []. The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric []. Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices [], and are mostly dimeric or multimeric, containing at least three conserved regions [,
,
]. However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c [].Lysine-tRNA synthesis is catalysed by two unrelated families of tRNA ligases: class-I or class-II. In eubacteria and eukaryota lysine-tRNA ligases belong to class II, the same family as aspartyl tRNA ligase. The lysine-tRNA ligase class Ic family is present in archaea and some eubacteria [
]. Moreover in some eubacteria there is a gene X, which is similar to a part of lysine-tRNA ligase from class II.Lysine-tRNA ligase is duplicated in some species with, for example in Escherichia coli, as a constitutive gene (lysS) and an induced one (lysU). No residues are directly involved in catalysis, but a number of highly conserved amino acids and three metal ions coordinate the substrates and stabilise the pentavalent transition state. Lysine is activated by being attached to the alpha-phosphate of AMP before being transferred to the cognate tRNA. The refined crystal structures give "snapshots"of the active site corresponding to key steps in the aminoacylation reaction and provide the structural framework for understanding the mechanism of lysine activation. The active site of LysU is shaped to position the substrates for the nucleophilic attack of the lysine carboxylate on the ATP alpha-phosphate. No residues are directly involved in catalysis, but a number of highly conserved amino acids and three metal ions coordinate the substrates and stabilise the pentavalent transition state. A loop close to the catalytic pocket, disordered in the lysine-bound structure, becomes ordered upon adenine binding [].
The GRIP (golgin-97, RanBP2alpha,Imh1p and p230/golgin-245) domain [
,
,
] is found in many large coiled-coil proteins. It has been shown to be sufficient for targeting to the Golgi []. The GRIP domain contains a completely conserved tyrosine residue.
This group includes nucleic acid independent RNA polymerases, such as polynucleotide adenylyltransferase (
), which adds the poly (A) tail to mRNA. This group also includes the tRNA nucleotidyltransferase that adds the CCA to the 3' of the tRNA (
).
CCA-adding enzymes add the sequence [cytidine(C)-cytidine-adenosine (A)]., one nucleotide at a time, onto the 3' end of tRNA, in a template-independent reaction [,
]. This Class II group is comprised mainly of eubacterial and eukaryotic enzymes and includes Bacillus stearothermophilus CCAase [], Escherichia coli poly(A) polymerase I [,
], human mitochondrial CCAase [,
], and Saccharomyces cerevisiae CCAase (CCA1) [,
,
]. CCA-adding enzymes have a single catalytic pocket, which recognizes both ATP and CTP substrates [,
]. This family belongs to the Pol beta-like NT superfamily [,
]. Escherichia coli CCAase is related to this group but has not been included in this alignment as this enzyme lacks the N-terminal helix conserved in the remainder of the NT superfamily.In the Pol beta-like NT superfamily [
,
], the majority of enzymes have two carboxylates, Dx[D/E], together with a third more distal carboxylate, which coordinate two divalent metal cations involved in a two-metal ion mechanism of nucleotide addition. These carboxylate residues are fairly well conserved in this family.
The alternative oxidase (AOX) is an enzyme that forms part of the electron transport chain in mitochondria of different organisms [
,
]. Proteins homologous to the mitochondrial oxidase have also been identified in bacterial genomes [,
]. The oxidase provides an alternative route for electrons passing through the electron transport chain to reduce oxygen. However, as several proton-pumping steps are bypassed in this alternative pathway, activation of the oxidase reduces ATP generation. This enzyme was first identified as a distinct oxidase pathway from cytochrome c oxidase as the alternative oxidase is resistant to inhibition by the poison cyanide [].The alternative oxidase (also known as ubiquinol oxidase) is used as a second terminal oxidase in the mitochondria, electrons are transferred directly from reduced ubiquinol to oxygen forming water [
]. This is not coupled to ATP synthesis and is not inhibited by cyanide, this pathway is a single step process []. In Oryza sativa (rice) the transcript levels of the alternative oxidase are increased by low temperature []. It has been predicted to contain a coupled diiron centre on the basis of a conserved sequence motif consisting of the proposed iron ligands, four Glu and two His residues []. The EPR study of Arabidopsis thaliana (mouse-ear cress) alternative oxidase AOX1a shows that the enzyme contains a hydroxo-bridged mixed-valent Fe(II)/Fe(III) binuclear iron centre []. A catalytic cycle has been proposed that involves a di-iron centre and at least one transient protein-derived radical, most probably an invariant Tyr residue [].
Several NAD- or NADP-dependent dehydrogenases, including 3-isopropylmalate dehydrogenase, tartrate dehydrogenase, and the multimeric forms of isocitrate dehydrogenase, share a nucleotide binding domain unrelated to that of lactate dehydrogenase and its homologues. These enzymes dehydrogenate their substates at a H-C-OH site adjacent to a H-C-COOH site; the latter carbon, now adjacent to a carbonyl group, readily decarboxylates.
Mitochondrial NAD-dependent isocitrate dehydrogenases (IDH) resemble prokaryotic NADP-dependent IDH and 3-isopropylmalate dehydrogenase (an NAD-dependent enzyme) more closely than they resemble eukaryotic NADP-dependent IDH. The mitochondrial NAD-dependent isocitrate dehydrogenase is believed to be an alpha(2)-beta-gamma heterotetramer. All subunits are homologous and belog to this group. The NADP-dependent IDH of Thermus thermophilus strain HB8 resembles these NAD-dependent IDH, except for the residues involved in cofactor specificity, much more closely than it resembles other prokaryotic NADP-dependent IDH, including that of Thermus aquaticus.
This homology domain, GlyGly-CTERM, shares a species distribution with rhombosortase (
), a subfamily of rhomboid-like intramembrane serine proteases [
]. It is probably a recognition sequence for protein sorting and then cleavage by rhombosortase. Shewanella species have the largest number of target proteins per genome, up to thirteen. The domain occurs at the extreme carboxyl-terminus of a diverse set of proteins, most of which are enzymes with conventional signal sequences and with hydrolytic activities: nucleases, proteases, agarases, etc. The agarase AgaA from Vibro sp. strain JT0107 is secreted into the medium, while the same protein heterologously expressed in E. coli is retained in the cell fraction []. This suggests cleavage and release in species with this domain. Both this suggestion, and the chemical structure of the domain (motif, hydrophobic predicted transmembrane helix, cluster of basic residues) closely parallels that of the LPXTG/sortase system and the PEP-CTERM/exosortase(EpsH) system. For this reason, the putative processing enzyme is designated rhombosortase.
CcmE is the product of a cluster of Ccm genes that are necessary for cytochrome c biosynthesis in many prokaryotes [
,
] and plant mitochondria []. In E. coli, expression of these proteins is induced when the organisms are grown under anaerobic conditions with nitrate or nitrite as the final electron acceptor [].
This family includes yeast Sem1 and its mammalian homologue, DSS1.Sem1/DSS1 (also known as rpn15) is a component of lid subcomplex of 26S proteasome regulatory subunit [
,
,
]. Besides being a subunit of the 26S proteasome, Sem1/DSS1 associates with other protein complexes []. It is a component of the nuclear pore complex (NPC)-associated TREX-2 complex that is required for transcription-coupled mRNA export, and the COP9 signalosome, which is involved in deneddylation [,
,
]. Loss of DSS1 in humans has been associated with split hand/split foot malformations [
].
Malonyl-CoA, in addition to being an intermediate in the de novosynthesis of fatty acids, is an inhibitor of carnitine palmitoyltransferase I, the enzyme that regulates the transfer of long-chain fatty acyl-CoA into mitochondria, where they are oxidised. After exercise, malonyl-CoA decarboxylase participates with acetyl-CoA carboxylase in regulating the concentration of malonyl-CoA in liver and adipose tissue, as well as in muscle. Malonyl-CoA decarboxylase is regulated by AMP-activated protein kinase (AMPK) [
].This entry represents the C-terminal catalytic domain of Malonyl-CoA decarboxylase [
].
Transcription initiation factor IIF, alpha subunit (TFIIF-alpha) or RNA polymerase II-associating protein 74 (RAP74) is the large subunit of transcription factor IIF (TFIIF), which is essential for accurate initiation and stimulates elongation by RNA polymerase II [
].
Transcription factor IIF (TFIIF), which is essential for eukaryotic transcription by RNA polymerase II. (PolII), consists of a heterodimer of Rap30 (beta) (
) and Rap74 (alpha) (
) subunits [
]. Rap30 and Rap74 have multiple domains that bind to PolII, TFIIB, TAF250 and DNA in interactions that are essential for transcription initiation and elongation. The N-terminal interactions domains of Rap30 and Rap74 are responsible for establishing the dimer interface between the two subunits, this interface being important for TFIIF function [].
The redox active metal copper is an essential cofactor in critical biological processes such as respiration, iron transport, oxidative stress protection, hormone production, and pigmentation. A widely conserved family of high-affinity copper transport proteins (Ctr proteins) mediates copper uptake at the plasma membrane [
]. A series of clustered methionine residues in the hydrophilic extracellular domain, and an MXXXM motif in the second transmembrane domain, are important for copper uptake. These methionines probably coordinate copper during the process of metal transport [].
Fumarylacetoacetase (
; also known as fumarylacetoacetate hydrolase or FAH) catalyses the hydrolytic cleavage of a carbon-carbon bond in fumarylacetoacetate to yield fumarate and acetoacetate as the final step in phenylalanine and tyrosine degradation [
]. This is an essential metabolic function in humans, the lack of FAH causing type I tyrosinaemia, which is associated with liver and kidney abnormalities and neurological disorders [,
]. The enzyme mechanism involves a catalytic metal ion, a Glu/His catalytic dyad, and a charged oxyanion hole []. FAH folds into two domains: an N-terminal domain SH3-like β-barrel, and a C-terminal with an unusual fold consisting of three layers of β-sheet structures [].This entry represents the N-terminal domain of fumarylacetoacetase. This domain adopts a structure consisting of an SH3-like barrel [
].
Fumarylacetoacetase (
; also known as fumarylacetoacetate hydrolase or FAH) catalyses the hydrolytic cleavage of a carbon-carbon bond in fumarylacetoacetate to yield fumarate and acetoacetate as the final step in phenylalanine and tyrosine degradation [
,
]. This is an essential metabolic function in humans, the lack of FAH causing type I tyrosinemia, which is associated with liver and kidney abnormalities and neurological disorders [,
]. The enzyme mechanism involves a catalytic metal ion, a Glu/His catalytic dyad, and a charged oxyanion hole []. FAH folds into two domains: an N-terminal domain SH3-like β-barrel, and a C-terminal with an unusual fold consisting of three layers of β-sheet structures [].In Aspergillus fumigatus, this enzyme is part of the L-tyrosine degradation gene cluster that mediates the biosynthesis of the brownish pigment pyomelanin as an alternative melanin [
,
].
Fumarylacetoacetase (
; also known as fumarylacetoacetate hydrolase or FAH) catalyses the hydrolytic cleavage of a carbon-carbon bond in fumarylacetoacetate to yield fumarate and acetoacetate as the final step in phenylalanine and tyrosine degradation [
]. This is an essential metabolic function in humans, the lack of FAH causing type I tyrosinaemia, which is associated with liver and kidney abnormalities and neurological disorders [,
]. The enzyme mechanism involves a catalytic metal ion, a Glu/His catalytic dyad, and a charged oxyanion hole []. FAH folds into two domains: an N-terminal domain SH3-like β-barrel, and a C-terminal with an unusual fold consisting of three layers of β-sheet structures [].This entry represents the C-terminal domain of fumarylacetoacetase, as well as other domains that share a homologous α/β structure, including:5-carboxymethyl-2-hydroxymuconate delta-isomerase (CHM isomerase;
), which catalyses the conversion of 5-carboxymethyl-2-hydroxymuconate to 5-carboxy-2-oxohept-3-enedioate [
].5-oxopent-3-ene-1,2,5-tricarboxylate decarboxylase (OPET decarboxylase;
), which catalyses the conversion of 5-oxopent-3-ene-1,2,5-tricarboxylate to 2-oxohept-3-enedioate and carbon dioxide.
Bifunctional enzyme HpcE (OPET decarboxylase
/HHDD isomerase
), which is a duplication consisting of a tandem repeat of two FAH C-terminal-like domains. This enzyme is responsible for the degradation of 4-hydroxyphenylacetate, a product of tyrosine and phenylalanine metabolism also released by lignin catabolism [
]. 2-keto-4-pentenoate hydratase MhpD (
; also known as 2-oxopent-4-enoate hydratase), which converts 4-hydroxy-2-oxopentanoate to 2-oxopent-4-enoate [
].4-oxalocrotonate decarboxylase (4-OD;
), which catalyses the conversion of 4-oxalocrotonate to 2-oxopent-4-enoate and carbon dioxide [
].2-oxo-hepta-3-ene-1,7-dioic acid hydratase, which hydrates the double bond of 2-oxo-hepta-3-ene-1,7-dioic acid to form 4-hydroxy-2-oxo-heptane-1,7-dioic acid in the catabolism of 4-hydroxyphenylacetic acid.
