cd16377, 23S_rRNA_IVP_like, 23S rRNA-intervening sequence protein and similar proteins. A family of functionally uncharacterized bacterial proteins, some of which are encoded by an atypically large intervening sequence present within some 23S rRNA genes. The distantly related bAvd protein, which also forms a homopentamer of four-helix bundles, has been suggested to interact with nucleic acids and a reverse transcriptase.
TIGR04183, hypothetical_protein, Por secretion system C-terminal sorting domain. Species that include Porphyromonas gingivalis, Fibrobacter succinogenes, Flavobacterium johnsoniae, Cytophaga hutchinsonii, Gramella forsetii, Prevotella intermedia, and Salinibacter ruber average twenty or more copies of a C-terminal domain, represented by this model, associated with sorting to the outer membrane and covalent modification.
TIGR03991, alt_bact_glmU, UDP-N-acetylglucosamine diphosphorylase/glucosamine-1-phosphate N-acetyltransferase. The MJ_1101 protein from Methanococcus jannaschii has been characterized as the GlmU enzyme catalyzing the final two steps of UDP-GlcNAc biosynthesis. Homologs of this enzyme are identified in a number of bacterial organisms and modeled here. A number of these are observed in proximity to the GlmS and GlmM genes, and phylogenetic profiling by PPP identifies the LEPBI_I0518 gene in Leptospira biflexa as a likely Glm-system candidate. Multiple sequence alignments of these bacterial homologs with their archaeal counterparts reveals significant structural differences, necessitating the construction of separate models. [Cell envelope, Biosynthesis and degradation of murein sacculus and peptidoglycan, Central intermediary metabolism, Amino sugars].
cd00717, URO-D, Uroporphyrinogen decarboxylase (URO-D) is a dimeric cytosolic enzyme that decarboxylates the four acetate side chains of uroporphyrinogen III (uro-III) to create coproporphyrinogen III, without requiring any prosthetic groups or cofactors. This reaction is located at the branching point of the tetrapyrrole biosynthetic pathway, leading to the biosynthesis of heme, chlorophyll or bacteriochlorophyll. URO-D deficiency is responsible for the human genetic diseases familial porphyria cutanea tarda (fPCT) and hepatoerythropoietic porphyria (HEP).
pfam12893, Lumazine_bd_2, Putative lumazine-binding. This is a family of uncharacterized proteins. However, the family belongs to the NTF2-like superfamily of various enzymes, and some of the members of the family are putative dehydrogenases.
pfam07264, EI24, Etoposide-induced protein 2.4 (EI24). This family contains a number of eukaryotic etoposide-induced 2.4 (EI24) proteins approximately 350 residues long as well as bacterial CysZ proteins (formerly known as DUF540). In cells treated with the cytotoxic drug etoposide, EI24 is induced by p53. It has been suggested to play an important role in negative cell growth control.
cd09604, M1_APN_like, Peptidase M1 family similar to aminopeptidase N catalytic domain. This family contains bacterial M1 peptidases with smilarity to the catalytic domain of aminopeptidase N (APN; CD13; alanyl aminopeptidase; EC 3.4.11.2), a type II integral membrane protease belonging to the M1 gluzincin family. APN preferentially cleaves neutral amino acids from the N-terminus of oligopeptides and, in higher eukaryotes, is present in a variety of human tissues and cell types (leukocyte, fibroblast, endothelial and epithelial cells). APN expression is dysregulated in inflammatory diseases such as chronic pain, rheumatoid arthritis, multiple sclerosis, systemic sclerosis, systemic lupus erythematosus, polymyositis/dermatomyosytis and pulmonary sarcoidosis, and is enhanced in tumor cells such as melanoma, renal, prostate, pancreas, colon, gastric and thyroid cancers. It is predominantly expressed on stem cells and on cells of the granulocytic and monocytic lineages at distinct stages of differentiation, thus considered a marker of differentiation. Thus, APN inhibition may lead to the development of anti-cancer and anti-inflammatory drugs. APNs are also present in many pathogenic bacteria and represent potential drug targets. Some APNs have been used commercially, such as one from Lactococcus lactis used in the food industry. APN also serves as a receptor for coronaviruses, although the virus receptor interaction site seems to be distinct from the enzymatic site and aminopeptidase activity is not necessary for viral infection. APNs have also been extensively studied as putative Cry toxin receptors. Cry1 proteins are pore-forming toxins that bind to the midgut epithelial cell membrane of susceptible insect larvae, causing extensive damage. Several different toxins, including Cry1Aa, Cry1Ab, Cry1Ac, Cry1Ba, Cry1Ca and Cry1Fa, have been shown to bind to APNs; however, a direct role of APN in cytotoxicity has been yet to be firmly established.
cd02000, TPP_E1_PDC_ADC_BCADC, Thiamine pyrophosphate (TPP) family, E1 of PDC_ADC_BCADC subfamily, TPP-binding module; composed of proteins similar to the E1 components of the human pyruvate dehydrogenase complex (PDC), the acetoin dehydrogenase complex (ADC) and the branched chain alpha-keto acid dehydrogenase/2-oxoisovalerate dehydrogenase complex (BCADC). PDC catalyzes the irreversible oxidative decarboxylation of pyruvate to produce acetyl-CoA in the bridging step between glycolysis and the citric acid cycle. ADC participates in the breakdown of acetoin while BCADC participates in the breakdown of branched chain amino acids. BCADC catalyzes the oxidative decarboxylation of 4-methyl-2-oxopentanoate, 3-methyl-2-oxopentanoate and 3-methyl-2-oxobutanoate (branched chain 2-oxo acids derived from the transamination of leucine, valine and isoleucine).
TIGR02224, Tyrosine_recombinase_XerC, tyrosine recombinase XerC. The phage integrase family describes a number of recombinases with tyrosine active sites that transiently bind covalently to DNA. Many are associated with mobile DNA elements, including phage, transposons, and phase variation loci. This model represents XerC, one of two closely related chromosomal proteins along with XerD (TIGR02225). XerC and XerD are site-specific recombinases which help resolve chromosome dimers to monomers for cell division after DNA replication. In species with a large chromosome and homologs of XerC on other replicons, the chomosomal copy was preferred for building this model. This model does not detect all XerC, as some apparent XerC examples score in the gray zone between trusted (450) and noise (410) cutoffs, along with some XerD examples. XerC and XerD interact with cell division protein FtsK. [DNA metabolism, DNA replication, recombination, and repair].
cd05254, dTDP_HR_like_SDR_e, dTDP-6-deoxy-L-lyxo-4-hexulose reductase and related proteins, extended (e) SDRs. dTDP-6-deoxy-L-lyxo-4-hexulose reductase, an extended SDR, synthesizes dTDP-L-rhamnose from alpha-D-glucose-1-phosphate, providing the precursor of L-rhamnose, an essential cell wall component of many pathogenic bacteria. This subgroup has the characteristic active site tetrad and NADP-binding motif. This subgroup also contains human MAT2B, the regulatory subunit of methionine adenosyltransferase (MAT); MAT catalyzes S-adenosylmethionine synthesis. The human gene encoding MAT2B encodes two major splicing variants which are induced in human cell liver cancer and regulate HuR, an mRNA-binding protein which stabilizes the mRNA of several cyclins, to affect cell proliferation. Both MAT2B variants include this extended SDR domain. Extended SDRs are distinct from classical SDRs. In addition to the Rossmann fold (alpha/beta folding pattern with a central beta-sheet) core region typical of all SDRs, extended SDRs have a less conserved C-terminal extension of approximately 100 amino acids. Extended SDRs are a diverse collection of proteins, and include isomerases, epimerases, oxidoreductases, and lyases; they typically have a TGXXGXXG cofactor binding motif. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold, an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Sequence identity between different SDR enzymes is typically in the 15-30% range; they catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase numbering). In addition to the Tyr and Lys, there is often an upstream Ser and/or an Asn, contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Atypical SDRs generally lack the catalytic residues characteristic of the SDRs, and their glycine-rich NAD(P)-binding motif is often different from the forms normally seen in classical or extended SDRs. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif.
cd00552, RaiA, RaiA ("ribosome-associated inhibitor A", also known as Protein Y (PY), YfiA, and SpotY, is a stress-response protein that binds the ribosomal subunit interface and arrests translation by interfering with aminoacyl-tRNA binding to the ribosomal A site. RaiA is also thought to counteract miscoding at the A site thus reducing translation errors. The RaiA fold structurally resembles the double-stranded RNA-binding domain (dsRBD).
pfam00584, SecE, SecE/Sec61-gamma subunits of protein translocation complex. SecE is part of the SecYEG complex in bacteria which translocates proteins from the cytoplasm. In eukaryotes the complex, made from Sec61-gamma and Sec61-alpha translocates protein from the cytoplasm to the ER. Archaea have a similar complex.
pfam02254, TrkA_N, TrkA-N domain. This domain is found in a wide variety of proteins. These protein include potassium channels, phosphoesterases, and various other transporters. This domain binds to NAD.
TIGR04183, hypothetical_protein, Por secretion system C-terminal sorting domain. Species that include Porphyromonas gingivalis, Fibrobacter succinogenes, Flavobacterium johnsoniae, Cytophaga hutchinsonii, Gramella forsetii, Prevotella intermedia, and Salinibacter ruber average twenty or more copies of a C-terminal domain, represented by this model, associated with sorting to the outer membrane and covalent modification.
TIGR00737, Probable_tRNA-dihydrouridine_synthase, putative TIM-barrel protein, nifR3 family. This model represents one branch of COG0042 (Predicted TIM-barrel enzymes, possibly dehydrogenases, nifR3 family). This branch includes NifR3 itself, from Rhodobacter capsulatus. It excludes a broadly distributed but more sparsely populated subfamily that contains sll0926 from Synechocystis PCC6803, HI0634 from Haemophilus influenzae, and BB0225 from Borrelia burgdorferi. It also excludes a shorter and more distant archaeal subfamily.The function of nifR3, a member of this family, is unknown, but it is found in an operon with nitrogen-sensing two component regulators in Rhodobacter capsulatus.Members of this family show a distant relationship to alpha/beta (TIM) barrel enzymes such as dihydroorotate dehydrogenase and glycolate oxidase. [Unknown function, General].
cd12152, F1-ATPase_delta, mitochondrial ATP synthase delta subunit. The F-ATPase is found in bacterial plasma membranes, mitochondrial inner membranes and in chloroplast thylakoid membranes. It has also been found in the archaea Methanosarcina barkeri. It uses a proton gradient to drive ATP synthesis and hydrolyzes ATP to build the proton gradient. The extrinisic membrane domain, F1, is composed of alpha, beta, gamma, delta, and epsilon subunits with a stoichiometry of 3:3:1:1:1. Alpha and beta subunit form the globular catalytic moiety, a hexameric ring of alternating subunits. Gamma, delta and epsilon subunits form a stalk, connecting F1 to F0, the integral membrane proton translocating domain. In bacteria, which is lacking a eukaryotic epsilon subunit homolog, this subunit is called the epsilon subunit.
cd02953, DsbDgamma, DsbD gamma family; DsbD gamma is the C-terminal periplasmic domain of the bacterial protein DsbD. It contains a CXXC motif in a TRX fold and shuttles the reducing potential from the membrane domain (DsbD beta) to the N-terminal periplasmic domain (DsbD alpha). DsbD beta, a transmembrane domain comprising of eight helices, acquires its reducing potential from the cytoplasmic thioredoxin. DsbD alpha transfers the acquired reducing potential from DsbD gamma to target proteins such as the periplasmic protein disulphide isomerases, DsbC and DsbG. This flow of reducing potential from the cytoplasm through DsbD allows DsbC and DsbG to act as isomerases in the oxidizing environment of the bacterial periplasm. DsbD also transfers reducing potential from the cytoplasm to specific reductases in the periplasm which are involved in the maturation of cytochromes.
cd01347, ligand_gated_channel, TonB dependent/Ligand-Gated channels are created by a monomeric 22 strand (22,24) anti-parallel beta-barrel. Ligands apparently bind to the large extracellular loops. The N-terminal 150-200 residues form a plug from the periplasmic end of barrel. Energy (proton-motive force) and TonB-dependent conformational alteration of channel (parts of plug, and loops 7 and 8) allow passage of ligand. FepA residues 12-18 form the TonB box, which mediates the interaction with the TonB-containing inner membrane complex. TonB preferentially interacts with ligand-bound receptors. Transport thru the channel may resemble passage thru an air lock. In this model, ligand binding leads to closure of the extracellular end of pore, then a TonB-mediated signal facillitates opening of the interior side of pore, deforming the N-terminal plug and allowing passage of the ligand to the periplasm. Such a mechanism would prevent the free diffusion of small molecules thru the pore.
TIGR02212, releasing_system_transmembrane_protein_lolC., lipoprotein releasing system, transmembrane protein, LolC/E family. This model describes the LolC protein, and its paralog LolE found in some species. These proteins are homologous to permease proteins of ABC transporters. In some species, two paralogs occur, designated LolC and LolE. In others, a single form is found and tends to be designated LolC. [Protein fate, Protein and peptide secretion and trafficking].
