NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]
X-RAY CRYSTALLOGRAPHY (3.20 ANGSTROMS) OF THE UNPHOSPHORYLATED UNPOLYGLYCYLATED FORM
MUTAGENESIS OF ARG-200; THR-208; THR-214; GLU-247 AND LYS-248
MUTAGENESIS OF LYS-53; VAL-183; THR-214; GLU-246 AND GLU-247
X-RAY CRYSTALLOGRAPHY (3.10 ANGSTROMS) OF THE UNPHOSPHORYLATED POLYGLYCYLATION MIMIC MUTANT AND IN COMPLEX WITH SYNTHETIC PHOSPHOPEPTIDE
Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner (By similarity). Binds with varying affinity to various synthetic phosphopeptides having a consensus binding motif RSX(pS/pT)XP, called mode-1, where X is any residue and pS/pT is a phosphorylated serine/threonine, and to synthetic phosphopeptides having a consensus binding motif Xp(S/T)X1-2-COOH, called mode-3, in which the phosphorylated residue occupies the penultimate C-terminal position in the target protein, but does not bind to their unphosphorylated counterparts (PubMed:19733174). Binds to synthetic human RAF1 phosphopeptides, but not to their unphosphorylated forms. Binds to difopein, a polypeptide containing a phosphorylation-independent binding motif (PubMed:16368691, PubMed:19733174). Involved in encystation (PubMed:19733174). Involved in cell proliferation. Required for actin and tubulin cytoskeletal organization. Regulates actin filament formation and nuclear size (PubMed:28932813).
Homodimer (PubMed:16368691, PubMed:24658679, PubMed:28932813, PubMed:26551337, PubMed:22452640). Homodimerizes via N-terminal domains (PubMed:24658679, PubMed:26551337). Oligomerizes forming homotrimers, homotetramers and protein filaments. Oligomerization is hindered by polyglycylation in vivo (PubMed:24658679). Interacts with a large number of both cytosolic and membrane proteins in trophozoites and encysting parasites (PubMed:16368691, PubMed:22452640). Interacts with a serine/threonine protein kinase GL50803_112076 (gCDC7). Component of a multiprotein complex containing gCDC7 and GL50803_94117 (gDBF4), a regulatory subunit of gCDC7, during both the trophozoite and encysting stages of the parasite. Interacts with fructose-bisphosphate aldolase GL50803_11043 (gFBA), pyruvate kinase GL50803_17143 (gPyk), acetyl-CoA synthetase GL50803_13608 (gACS), protein kinase GL50803_22165 (gSTE), DEAD box RNA helicase GL50803_34684 (gVASA) and Golgi/cell cycle associated protein GL50803_17472 (gGCCA) (PubMed:22452640). Interacts with actin (PubMed:24728194, PubMed:28932813). Interacts with both monomeric phosphorylated and unphosphorylated actin. The interaction is enhanced by phosphorylation of actin and inhibited by Rho GTPase Rac (PubMed:28932813).
In trophozoites and cysts, localizes intensely in the cytoplasm. Not detected in the central area of the cell corresponding to the median body nor in flagella. Detected in the nuclei of the encysting cells. Nuclear localization increases during the transition of cells from the early to the late encysting stage. Does not localize to the encystation-specific vesicles of the encysting cells (PubMed:16368691, PubMed:19733174). In interphase cells, detected throughout the cell with somewhat enriched at the cortex and perinuclear region. Associates with the intracytoplasmic axonemes of all flagella, but it is most apparent in the anterior flagella of interphase cells. Localizes also to the nuclear envelope/endoplasmic reticulum and to the microtubule bare area of the ventral disc during interphase. In mitotic cells, disassociates from the intracytoplasmic axonemes and localizes around the spindle. During cytokinesis, localizes with the ingressing furrow, which does not utilize a contractile ring (PubMed:28932813). Does no colocalize with F-actin (PubMed:24728194, PubMed:28932813).
Expressed during excystation, the differentiation from cyst to trophozoite (at protein level) (PubMed:19861170). Expressed in trophozoites (at protein level) (PubMed:24658679, PubMed:19733174, PubMed:24147113, PubMed:24728194, PubMed:28932813, PubMed:22452640, PubMed:23058231, PubMed:21135098). Highly expressed during encystation stage, the differentiation from trophozoite to cyst (at protein level) (PubMed:24658679, PubMed:19733174, PubMed:24147113, PubMed:22452640). Expressed in feces extracted cysts (at protein level) (PubMed:19861170, PubMed:23058231). Expression in them is significantly lower than in trophozoites (at protein level) (PubMed:23058231). Constitutively expressed throughout the life cycle (PubMed:16368691).
Phosphorylated constitutively throughout the life cycle. Phosphorylation is very high in trophozoites and encysting cells of 12 hours (PubMed:16368691). Phosphorylated during excystation (PubMed:19861170). Phosphorylation promotes its binding to various target proteins and is critical for encystation process. Phosphorylation modification is not influenced by polyglycylation modification (PubMed:19733174).
Polyglycylated on a glutamate residue, resulting in polyglycine chain on the gamma-carboxyl group (PubMed:16368691, PubMed:24658679, PubMed:19733174, PubMed:24147113, PubMed:21135098). Polyglycylated by the tubulin--tyrosine ligase-like protein GL50803_8456 (gTTLL3). The polyglycine chain is shortened by metallopeptidases of the M20 family, namely dipeptidases GL50803_15832 (gDIP1) and GL50803_8407 (gDIP2) (PubMed:21135098). The length of the polyglycine chain is developmental stage-dependent. In trophozoites, glycine residues range from 10 to 31, with the greatest occurrence of 21 residues. In 12 hour encystation stage, glycine residues range from 6 to 22, with the greatest occurrence of 10 residues. The differential rate of polyglycylation/deglycylation during the encystation process regulates the intracellular localization of this protein. Relocalizes partially from the cytoplasm inside the nuclei following the shortening of the polyglycine chain in encysting cells (PubMed:16368691, PubMed:19733174). Polyglycylation modification is not influenced by phosphorylation modification (PubMed:19733174). Polyglycylation prevents oligomerization in vivo (PubMed:24658679).
Knockdown with morpholino results in dramatically reduced parasite growth, accumulation of multinucleate cells, abnormal flagellar positioning, and polarity and cytokinesis defects. Overall cytoplasmic actin organization is disrupted with ectopic short actin filaments, however, nuclei are enlarged with actin filaments covering the width of the nuclei.
This protein may be used to design small molecules that inhibit its interactions with the target proteins. The inhibitors could be used as drugs to treat giardiasis, a disease caused by this parasite.
Despite sequential and structural similarity, is not a functional ortholog of Drosophila 14-3-3 protein epsilon.
Putative polyglycylation target motif (T/G)X0-1(D/E)X1-3-G(D/E)X1-2(gE)2-4, where X is polar or negatively charged amino acid, and gE is polyglycylated glutamine
Loss or strongly decreased binding to synthetic human RAF1 phosphopeptides. Loss of binding to difopein.
Loss of phosphorylation by a protein kinase. No effect on subcellular localization. Dramatic decrease in the number of encysting parasites and cysts, but a large increase in the number of trophozoites. In encysting cells of 12 hours, significantly slower cyst conversion rate compared to the wild-type. No effect on binding to difopein. Decreased binding to a number of synthetic phosphopeptides.
Phosphomimetic mutant. No effect on oligomerization. No effect on binding to difopein. Altered binding intensity or capability to various synthetic phosphopeptides.
Loss of polyglycylation. In trophozoites, encysting cells and cysts, localizes to the nuclei in addition to the cytoplasm. Increased encystation and increased number of cysts. In encysting cells of 12 hours, significantly faster cyst conversion rate compared to the wild-type.
Prevention of oligomerization and filament formation by the polyglycylation of E-246; when associated with K-248 del.
Prevention of oligomerization and filament formation by the polyglycylation of E-246; when associated with E-247 del.
Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
Ribonuclease H-like superfamily/Ribonuclease H
EUKARYOTIC TRANSLATION INITIATION FACTOR 2C
Plays an essential role in growth and, with Dicer, also involved in microRNA (miRNA)-mediated translational repression. The RNA interference pathway is implicated in antigenic variation having a role in regulation of variant-specific surface protein (VSP)-coding gene expression. Several VSP genes are transcribed but only transcripts encoding the VSP to be expressed accumulate. Antisense RNAs corresponding to the silenced VSP genes are detected (By similarity).
Interacts with miR2. Highly specific binding to the mRNA m7G-cap. May be a component of the RNA-induced silencing complex (RISC), a sequence-specific, multicomponent nuclease that destroys or silences messenger RNAs homologous to the silencing trigger (By similarity).
PAZ domain is absent, but Ago is capable of binding small RNAs in the same way as the other Argonaute proteins.
Belongs to the argonaute family. Ago subfamily.
Plays an essential role in growth and, with Dicer, also involved in microRNA (miRNA)-mediated translational repression. The RNA interference pathway is implicated in antigenic variation having a role in regulation of variant-specific surface protein (VSP)-coding gene expression. Several VSP genes are transcribed but only transcripts encoding the VSP to be expressed accumulate. Antisense RNAs corresponding to the silenced VSP genes are detected.
Interacts with miR2. Highly specific binding to the mRNA m7G-cap. May be a component of the RNA-induced silencing complex (RISC), a sequence-specific, multicomponent nuclease that destroys or silences messenger RNAs homologous to the silencing trigger.
Inhibited cell growth due to inhibition of translation initiation. A change from single to multiple VSP expression in individual parasites.
New Giardia intestinalis WB genome in near-complete chromosomes.
X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) IN COMPLEX WITH ZINC AND SUBSTRATE TRANSITION STATE ANALOG PHOSPHOGLYCOLOHYDROXAMATE
X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF WILD TYPE AND MUTANT ALA-83 IN COMPLEX WITH ZINC; FRUCTOSE 1,6-BISPHOSPHATE AND SUBSTRATE ANALOG TAGATOSE 1,6-BISPHOSPHATE
X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEX WITH ZINC AND INHIBITOR
D-TAGATOSE-1,6-BISPHOSPHATE ALDOLASE SUBUNIT GATY-RELATED
Plays a key role in glycolysis by catalyzing the cleavage of fructose 1,6-bisphosphate into dihydroxyacetone phosphate and glyceraldehyde 3-phosphate (PubMed:17166851). Does not cleave D-tagatose-1,6-bisphosphate (PubMed:17166851, PubMed:19236002).
kcat is 3.55 sec(-1) with fructose 1,6-bisphosphate as substrate (at pH 7.5 and 25 degrees Celsius) (PubMed:17166851). kcat is 4.3 sec(-1) with fructose 1,6-bisphosphate as substrate (PubMed:31409864).
1.7 uM for fructose 1,6-bisphosphate (at pH 7.5 and 25 degrees Celsius)
Expressed in trophozoites (at protein level).
Belongs to the class II fructose-bisphosphate aldolase family.
9.4-fold reduction in substrate affinity and 50-fold reduction in catalytic affinity. Has some activity towards tagatose-1,6-bisphosphate.
1.8-fold reduction in substrate affinity and 2.8-fold reduction in catalytic efficiency. 6-fold reduction in substrate affinity and 24-fold reduction in catalytic efficiency; when associated with A-278.
159-fold reduction in substrate affinity and 2770-fold reduction in catalytic efficiency. 6-fold reduction in substrate affinity and 24-fold reduction in catalytic efficiency; when associated with A-259.
DOLICHYL-PHOSPHATE BETA-GLUCOSYLTRANSFERASE
Dolichyl-phosphate beta-glucosyltransferase ALG5A
Dolichyl-phosphate beta-glucosyltransferase involved in the glycosylation of glycoproteins through the synthesis of dolichyl beta-D-glucosyl phosphate which serves as a sugar donor for transfer of three glucose residues to the Man-9-GlcNAc-2-PP-dolichol precursor to N-glycans.
Belongs to the glycosyltransferase 2 family.
Helical; Signal-anchor for type II membrane protein
Dolichyl-phosphate beta-glucosyltransferase ALG5B
Dolichyl-phosphate beta-glucosyltransferase ALG5C
Dolichyl-phosphate beta-glucosyltransferase ALG5D
Dolichyl-phosphate beta-glucosyltransferase ALG5E
May function as a calcium-regulated structural element linking phospholipid bilayer and underlying axoneme.
A pair of annexin repeats may form one binding site for calcium and phospholipid.
P-loop containing nucleotide triphosphate hydrolases
P-loop containing nucleoside triphosphate hydrolases
GTP-binding protein involved in protein trafficking; may modulate vesicle budding and uncoating within the Golgi apparatus.
Belongs to the small GTPase superfamily. Arf family.
ARSENICAL PUMP-DRIVING ATPASE ARSENITE-TRANSLOCATING ATPASE
ATPase required for the post-translational delivery of tail-anchored (TA) proteins to the endoplasmic reticulum. Recognizes and selectively binds the transmembrane domain of TA proteins in the cytosol. This complex then targets to the endoplasmic reticulum by membrane-bound receptors, where the tail-anchored protein is released for insertion. This process is regulated by ATP binding and hydrolysis. ATP binding drives the homodimer towards the closed dimer state, facilitating recognition of newly synthesized TA membrane proteins. ATP hydrolysis is required for insertion. Subsequently, the homodimer reverts towards the open dimer state, lowering its affinity for the membrane-bound receptor, and returning it to the cytosol to initiate a new round of targeting.
Specifically acetylates 'Lys-40' in alpha-tubulin on the lumenal side of microtubules. Promotes microtubule destabilization and accelerates microtubule dynamics; this activity may be independent of acetylation activity. Acetylates alpha-tubulin with a slow enzymatic rate, due to a catalytic site that is not optimized for acetyl transfer. Enters the microtubule through each end and diffuses quickly throughout the lumen of microtubules. Acetylates only long/old microtubules because of its slow acetylation rate since it does not have time to act on dynamically unstable microtubules before the enzyme is released.
Belongs to the acetyltransferase ATAT1 family.
Type I PLP-dependent aspartate aminotransferase-like (Major domain)
BETA-ELIMINATING LYASE-LIKE PROTEIN-RELATED
Belongs to the beta-eliminating lyase family.
Basic immunoglobulin-like variable motif-containing protein
Cysteine-rich, antigenically variant surface protein.
This protein is found only in group 3 isolates.
Thiol protease which is required for parasite excystation and invasion of the proximal small intestine of the human host.
To initiate infection, trophozoites emerge from a cyst in the host. Excystation is blocked by specific cysteine protease inhibitors. Vacuoles release it just prior to excystation.
Not expressed without supplemental iron.
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 71-268
To initiate infection, trophozoites emerge from a cyst in the host. Excystation is blocked by specific cysteine protease inhibitors. Vacuoles release it just prior to excystation. Expressed in replicating and encysting trophozoites without supplemental iron.
Plays a fundamental role in microtubule-organizing center structure and function.
Centrosome of interphase and mitotic cells.
Binds two moles of calcium per mole of protein.
TCP-1-like chaperonin intermediate domain
60 KDA HEAT SHOCK PROTEIN, MITOCHONDRIAL
Implicated in hydrogenosomal protein import and macromolecular assembly. May facilitate the correct folding of imported proteins. May also prevent misfolding and promote the refolding and proper assembly of unfolded polypeptides generated under stress conditions in the hydrogenosome (Potential).
Belongs to the chaperonin (HSP60) family.
X-RAY CRYSTALLOGRAPHY (3.33 ANGSTROMS) IN COMPLEX WITH MANGANESE
X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) IN COMPLEX WITH MANGANESE
Involved in cleaving double-stranded RNA in the RNA interference (RNAi) pathway. It produces 21 to 23 bp dsRNAs (siRNAs) which target the selective destruction of homologous RNAs.
Binds 2 magnesium or manganese ions per subunit.
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 59-261
Glutamate Dehydrogenase, chain A, domain 3
Leucine Dehydrogenase, chain A, domain 1
NADP-SPECIFIC GLUTAMATE DEHYDROGENASE 1-RELATED
Aminoacid dehydrogenase-like, N-terminal domain
Belongs to the Glu/Leu/Phe/Val dehydrogenases family.
May be involved in metabolism of dipeptides or may affect host defense mechanisms.
Expressed throughout the life cycle, but expression is slightly decreased during encystation.
Expression increased in response to the protease inhibitor bestatin.
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 40-273
EF-Tu/eEF-1alpha/eIF2-gamma C-terminal domain
This protein promotes the GTP-dependent binding of aminoacyl-tRNA to the A-site of ribosomes during protein biosynthesis.
Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. EF-Tu/EF-1A subfamily.
EUKARYOTIC PEPTIDE CHAIN RELEASE FACTOR SUBUNIT 1
N-terminal domain of eukaryotic peptide chain release factor subunit 1, ERF1
Directs the termination of nascent peptide synthesis (translation) in response to the termination codons UAA, UAG and UGA.
Heterodimer of two subunits, one of which binds GTP.
Belongs to the eukaryotic release factor 1 family.
S-adenosyl-L-methionine-dependent methyltransferases
S-adenosyl-L-methionine-dependent methyltransferase that has the ability to methylate both RNAs and proteins. Involved in pre-rRNA processing. Utilizes the methyl donor S-adenosyl-L-methionine to catalyze the site-specific 2'-hydroxyl methylation of ribose moieties in pre-ribosomal RNA. Site specificity is provided by a guide RNA that base pairs with the substrate. Methylation occurs at a characteristic distance from the sequence involved in base pairing with the guide RNA. Also acts as a protein methyltransferase by mediating methylation of 'Gln-105' of histone H2A (H2AQ105me), a modification that impairs binding of the FACT complex and is specifically present at 35S ribosomal DNA locus (By similarity).
Component of box C/D small nucleolar ribonucleoprotein (snoRNP) particles. It is associated with the U3, U8 and U13 small nuclear RNAs.
By homology to other fibrillarins, some or all of the N-terminal domain arginines are modified to asymmetric dimethylarginine (DMA).
Belongs to the methyltransferase superfamily. Fibrillarin family.
5' to 3' exonuclease, C-terminal subdomain
Structure-specific nuclease with 5'-flap endonuclease and 5'-3' exonuclease activities involved in DNA replication and repair. During DNA replication, cleaves the 5'-overhanging flap structure that is generated by displacement synthesis when DNA polymerase encounters the 5'-end of a downstream Okazaki fragment. It enters the flap from the 5'-end and then tracks to cleave the flap base, leaving a nick for ligation. Also involved in the long patch base excision repair (LP-BER) pathway, by cleaving within the apurinic/apyrimidinic (AP) site-terminated flap. Acts as a genome stabilization factor that prevents flaps from equilibrating into structures that lead to duplications and deletions. Also possesses 5'-3' exonuclease activity on nicked or gapped double-stranded DNA, and exhibits RNase H activity. Also involved in replication and repair of rDNA and in repairing mitochondrial DNA.
Binds 2 magnesium ions per subunit. They probably participate in the reaction catalyzed by the enzyme. May bind an additional third magnesium ion after substrate binding.
Interacts with PCNA. Three molecules of FEN1 bind to one PCNA trimer with each molecule binding to one PCNA monomer. PCNA stimulates the nuclease activity without altering cleavage specificity.
Resides mostly in the nucleoli and relocalizes to the nucleoplasm upon DNA damage.
Phosphorylated. Phosphorylation upon DNA damage induces relocalization to the nuclear plasma.
Belongs to the XPG/RAD2 endonuclease family. FEN1 subfamily.
X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 9-100
Ferredoxins are iron-sulfur proteins that transfer electrons in a wide variety of metabolic reactions. It links pyruvate:ferredoxin oxidoreductase to hydrogenase.
The propeptide may play a role in the targeting of this protein to the organelle.
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 14-312
GLYCERALDEHYDE 3-PHOSPHATE DEHYDROGENASE
GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE-RELATED
Glyceraldehyde-3-phosphate dehydrogenase-like, C-terminal domain
Glyceraldehyde-3-phosphate dehydrogenase 1
Belongs to the glyceraldehyde-3-phosphate dehydrogenase family.
Giardins are involved in parasite attachment to the intestinal mucosa and in the cytoskeletal disassembly and reassembly that marks the transition from infectious trophozoite to transmissible cyst. They may interact with other cytoskeletal proteins such as microtubules in the microribbons or crossbridges, to maintain the integrity of the ventral disk.
Most likely in the edges of the ventral disk microribbons.
Belongs to the annexin family. Giardin subunit alpha subfamily.
Giardins are involved in parasite attachment to the intestinal mucosa and in the cytoskeletal disassembly and reassembly that marks the transition from infectious trophozoite to transmissible cyst. They may interact with other cytoskeletal proteins such as microtubules in the microribbons or crossbridges, to maintain the integrity of the ventral disk (By similarity).
Shows an alpha-helical coiled coil structure (35 repeating heptads) related to the alpha-type fibrous proteins (K-M-E-F class).
Belongs to the bacterial glucokinase family.
Cloning of two Giardia glucosamine 6-phosphate isomerase genes only one of which is transcriptionally activated during encystment.
Belongs to the glucosamine/galactosamine-6-phosphate isomerase family.
GUANINE NUCLEOTIDE-BINDING PROTEIN SUBUNIT ALPHA HOMOLOG
Transducin (alpha subunit), insertion domain
Guanine nucleotide-binding protein subunit alpha-1
Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems.
G proteins are composed of 3 units; alpha, beta and gamma. The alpha chain contains the guanine nucleotide binding site.
HYPOXANTHINE-GUANINE PHOSPHORIBOSYLTRANSFERASE
Hypoxanthine-guanine-xanthine phosphoribosyltransferase
Essential in nucleic acid metabolism of T.foetus because the parasite is unable to synthesize purine nucleotides de novo and relies on the HGXPRTase activities for its purine requirements by salvaging purine bases from the host. Works with guanine, hypoxanthine and xanthine.
Binds 2 magnesium ions per subunit. The magnesium ions are essentially bound to the substrate and have few direct interactions with the protein.
Belongs to the purine/pyrimidine phosphoribosyltransferase family.
Nucleotide-binding domain of ferredoxin-NADP reductase (FNR) module
Ferredoxin reductase-like, C-terminal NADP-linked domain
Flavohemoprotein involved in nitric oxide (NO) detoxification in an aerobic process, termed nitric oxide dioxygenase (NOD) reaction that utilizes O(2) and NAD(P)H to convert NO to nitrate, which protects the protozoan parasite from various noxious nitrogen compounds. Therefore, plays a central role in the inducible response to nitrosative stress. May also be involved in O(2) detoxification (By similarity).
Consists of two distinct domains; an N-terminal heme-containing oxygen-binding domain and a C-terminal reductase domain with binding sites for FAD and NAD(P)H.
Belongs to the globin family. Two-domain flavohemoproteins subfamily.
In the C-terminal section; belongs to the flavoprotein pyridine nucleotide cytochrome reductase family.
Involved in heme-bound ligand stabilization and O-O bond activation
Influences the redox potential of the prosthetic heme and FAD groups
Flavohemoprotein involved in nitric oxide (NO) detoxification in an aerobic process, termed nitric oxide dioxygenase (NOD) reaction that utilizes O(2) and NAD(P)H to convert NO to nitrate, which protects the protozoan parasite from various noxious nitrogen compounds. Therefore, plays a central role in the inducible response to nitrosative stress. May also be involved in O(2) detoxification.
Expressed at very low levels in untreated trophozoites of the parasite. Expression is markedly stimulated in nitrite-supplemented medium. Induction by nitrite is probably mediated by NO, likely generated upon reduction of nitrite. Also induced in cells grown in the presence of the NO-donors 3,3-bis(aminoethyl)-1-hydroxy-2-oxo-1-triazene (DETA-NONOate), and S-nitrosoglutathione (GSNO).
EUKARYOTIC TRANSLATION INITIATION FACTOR 2 SUBUNIT 3 FAMILY MEMBER
EUKARYOTIC TRANSLATION INITIATION FACTOR 2 SUBUNIT 3-RELATED
Eukaryotic translation initiation factor 2 subunit gamma
As a subunit of eukaryotic initiation factor 2 (eIF-2), involved in the early steps of protein synthesis. In the presence of GTP, eIF-2 forms a ternary complex with initiator tRNA Met-tRNAi and then recruits the 40S ribosomal complex and initiation factors eIF-1, eIF-1A and eIF-3 to form the 43S pre-initiation complex (43S PIC), a step that determines the rate of protein translation. The 43S PIC binds to mRNA and scans downstream to the initiation codon, where it forms a 48S initiation complex by codon-anticodon base pairing. This leads to the displacement of eIF-1 to allow GTPase-activating protein (GAP) eIF-5-mediated hydrolysis of eIF2-bound GTP. Hydrolysis of GTP and release of Pi, which makes GTP hydrolysis irreversible, causes the release of the eIF-2-GDP binary complex from the 40S subunit, an event that is essential for the subsequent joining of the 60S ribosomal subunit to form an elongation-competent 80S ribosome. In order for eIF-2 to recycle and catalyze another round of initiation, the GDP bound to eIF-2 must be exchanged with GTP by way of a reaction catalyzed by GDP-GTP exchange factor (GEF) eIF-2B.
Eukaryotic translation initiation factor 2 (eIF-2) is a heterotrimeric G-protein composed of an alpha, a beta and a gamma subunit. The factors eIF-1, eIF-2, eIF-3, TIF5/eIF-5 and methionyl-tRNAi form a multifactor complex (MFC) that may bind to the 40S ribosome.
Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. EIF2G subfamily.
X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 4-377 IN COMPLEX WITH SUBSTRATE AND INHIBITOR
X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) IN COMPLEX WITH INHIBITOR
X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 4-377 IN COMPLEX WITH INHIBITOR (MIZORIBINE MONOPHOSPHATE; MZP) AND POTASSIUM
X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1-483 IN COMPLEX WITH SUBSTRATE; PRODUCT; INHIBITOR (MYCOPHENOLIC ACID; MPA) AND NAD(+)
INOSINE-5-MONOPHOSPHATE DEHYDROGENASE RELATED
Inosine monophosphate dehydrogenase (IMPDH)
Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth. Could also have a single-stranded nucleic acid-binding activity and could play a role in RNA and/or DNA metabolism.
Mycophenolic acid (MPA) is a non-competitive inhibitor that prevents formation of the closed enzyme conformation by binding to the same site as the amobile flap. In contrast, mizoribine monophosphate (MZP) is a competitive inhibitor that induces the closed conformation. MPA is a potent inhibitor of mammalian IMPDHs but a poor inhibitor of the bacterial enzymes. MZP is a more potent inhibitor of bacterial IMPDH.
Contains 2 potassium ions bound at each subunit interface. The second potassium binding site is not conserved and not observed in crystal structures of IMPDHs from other organisms (PubMed:12403633).
Has less than 0.06% of the wild-type activity.
ligand shared between two tetrameric partners
INOSINE TRIPHOSPHATE PYROPHOSPHATASE/HAM1 PROTEIN
Non-canonical purine NTP pyrophosphatase
Pyrophosphatase that hydrolyzes non-canonical purine nucleotides such as inosine triphosphate (ITP), deoxyinosine triphosphate (dITP) or xanthosine 5'-triphosphate (XTP) to their respective monophosphate derivatives. The enzyme does not distinguish between the deoxy- and ribose forms. Probably excludes non-canonical purines from RNA and DNA precursor pools, thus preventing their incorporation into RNA and DNA and avoiding chromosomal lesions.
Binds 1 divalent metal cation per subunit; can use either Mg(2+) or Mn(2+).
Microbial and mitochondrial ADK, insert 'zinc finger' domain
Catalyzes the reversible transfer of the terminal phosphate group between ATP and AMP. Plays an important role in cellular energy homeostasis and in adenine nucleotide metabolism.
Nuclear chaperone required for maturation and nuclear export of pre-60S ribosome subunits. Functions at successive maturation steps to remove ribosomal factors at critical transition points, first driving the exit of early pre-60S particles from the nucleolus and then driving late pre-60S particles from the nucleus.
Associates with pre-60S ribosomes in the nucleoplasm.
May have a role in immobilizing the microtubules between cell divisions.
Shows an alpha-helical coiled coil structure (30 repeating heptads).
Catalyzes the epimerization of the S- and R-forms of NAD(P)HX, a damaged form of NAD(P)H that is a result of enzymatic or heat-dependent hydration. This is a prerequisite for the S-specific NAD(P)H-hydrate dehydratase to allow the repair of both epimers of NAD(P)HX (By similarity).
UDP-N-ACETYLGLUCOSAMINE--PEPTIDE N-ACETYLGLUCOSAMINYLTRANSFERASE 110 KDA SUBUNIT
UDP-N-acetylglucosamine--peptide N-acetylglucosaminyltransferase
O-linked N-acetylglucosaminyltransferase
Catalyzes the transfer of a single N-acetylglucosamine from UDP-GlcNAc to a serine or threonine residue in cytoplasmic and nuclear proteins resulting in their modification with a beta-linked N-acetylglucosamine (O-GlcNAc).
The TPR repeat domain is required for substrate binding and oligomerization.
Belongs to the glycosyltransferase 41 family. O-GlcNAc transferase subfamily.
PYROPHOSPHATE--FRUCTOSE 6-PHOSPHATE 1-PHOSPHOTRANSFERASE
PYROPHOSPHATE--FRUCTOSE 6-PHOSPHATE 1-PHOSPHOTRANSFERASE SUBUNIT BETA 2
Pyrophosphate--fructose 6-phosphate 1-phosphotransferase 1
6-phosphofructokinase, pyrophosphate dependent 1
Pyrophosphate-dependent 6-phosphofructose-1-kinase 1
Catalyzes the phosphorylation of D-fructose 6-phosphate, the first committing step of glycolysis. Uses inorganic phosphate (PPi) as phosphoryl donor instead of ATP like common ATP-dependent phosphofructokinases (ATP-PFKs), which renders the reaction reversible, and can thus function both in glycolysis and gluconeogenesis. Consistently, PPi-PFK can replace the enzymes of both the forward (ATP-PFK) and reverse (fructose-bisphosphatase (FBPase)) reactions.
Belongs to the phosphofructokinase type A (PFKA) family. PPi-dependent PFK group II subfamily. Clade 'Short' sub-subfamily.
Important for catalytic activity and substrate specificity; stabilizes the transition state when the phosphoryl donor is PPi; prevents ATP from binding by mimicking the alpha-phosphate group of ATP
Important for catalytic activity; stabilizes the transition state when the phosphoryl donor is PPi
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-210
Pyrophosphate--fructose 6-phosphate 1-phosphotransferase 2
6-phosphofructokinase, pyrophosphate dependent 2
Pyrophosphate-dependent 6-phosphofructose-1-kinase 2
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-211
Pyrophosphate--fructose 6-phosphate 1-phosphotransferase 3
6-phosphofructokinase, pyrophosphate dependent 3
Pyrophosphate-dependent 6-phosphofructose-1-kinase 3
Translation C-terminally shortened because of gaps in the genomic sequence.
6-phosphofructokinase, pyrophosphate dependent
Pyrophosphate-dependent 6-phosphofructose-1-kinase
Non-allosteric. Competitively inhibited by fructose 2,6-bisphosphate.
4.62 umol/min/mg enzyme for the forward reaction
0.15 umol/min/mg enzyme for the reverse reaction
Optimum pH is 7.2 for the forward reaction and 7.0 for the reverse reaction.
Belongs to the phosphofructokinase type A (PFKA) family. PPi-dependent PFK group II subfamily. Clade 'Long' sub-subfamily.
PYRUVATE, PHOSPHATE DIKINASE 1, CHLOROPLASTIC
Glutathione synthetase ATP-binding domain-like
Catalyzes the reversible phosphorylation of pyruvate and phosphate.
Activated by light-induced dephosphorylation. Inhibited by dark-induced phosphorylation. Both reactions are catalyzed by PDRP1 (By similarity).
The N-terminal domain contains the ATP/Pi binding site, the central domain the pyrophosphate/phosphate carrier histidine, and the C-terminal domain the pyruvate binding site.
Phosphorylation of Thr-462 in the dark inactivates the enzyme. Dephosphorylation upon light stimulation reactivates the enzyme (By similarity).
The reaction takes place in three steps, each mediated by a carrier histidine residue located on the surface of the central domain. The two first partial reactions are catalyzed at an active site located on the N-terminal domain, and the third partial reaction is catalyzed at an active site located on the C-terminal domain. For catalytic turnover, the central domain swivels from the concave surface of the N-terminal domain to that of the C-terminal domain.
Belongs to the PEP-utilizing enzyme family.
Evidence for the existence of a 26S proteasome in Giardia lamblia.
Glutamine Phosphoribosylpyrophosphate, subunit 1, domain 1
N-terminal nucleophile aminohydrolases (Ntn hydrolases)
Non-catalytic component of the proteasome, a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity (By similarity).
The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is composed of 28 subunits that are arranged in four stacked rings, resulting in a barrel-shaped structure. The two end rings are each formed by seven alpha subunits, and the two central rings are each formed by seven beta subunits. The catalytic chamber with the active sites is on the inside of the barrel (By similarity).
GTP-binding protein involved in nucleocytoplasmic transport. Required for the import of protein into the nucleus and also for RNA export. Involved in chromatin condensation and control of cell cycle (By similarity).
Found in a nuclear export complex with RanGTP, exportin and pre-miRNA (By similarity).
Belongs to the small GTPase superfamily. Ran family.
DNA-DIRECTED RNA POLYMERASE III SUBUNIT RPC1
beta and beta-prime subunits of DNA dependent RNA-polymerase
DNA-directed RNA polymerase III largest subunit
DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Largest and catalytic core component of RNA polymerase III which synthesizes small RNAs, such as 5S rRNA and tRNAs. Forms the polymerase active center together with the second largest subunit. A single-stranded DNA template strand of the promoter is positioned within the central active site cleft of Pol III. A bridging helix emanates from RPC1 and crosses the cleft near the catalytic site and is thought to promote translocation of Pol III by acting as a ratchet that moves the RNA-DNA hybrid through the active site by switching from straight to bent conformations at each step of nucleotide addition (By similarity).
Component of the RNA polymerase III (Pol III) complex consisting of 17 subunits.
Belongs to the RNA polymerase beta' chain family.
Component of the small ribosomal subunit. Mature ribosomes consist of a small (40S) and a large (60S) subunit. The 40S subunit contains about 33 different proteins and 1 molecule of RNA (18S). The 60S subunit contains about 49 different proteins and 3 molecules of RNA (25S, 5.8S and 5S).
Belongs to the eukaryotic ribosomal protein eS1 family.
Required for the assembly and/or stability of the 40S ribosomal subunit. Required for the processing of the 20S rRNA-precursor to mature 18S rRNA in a late step of the maturation of 40S ribosomal subunits.
Component of the small ribosomal subunit. Mature ribosomes consist of a small (40S) and a large (60S) subunit. The 40S subunit contains about 33 different proteins and 1 molecule of RNA (18S). The 60S subunit contains about 49 different proteins and 3 molecules of RNA (25S, 5.8S and 5S). Interacts with ribosomal protein S21.
Belongs to the universal ribosomal protein uS2 family.
Formate/glycerate dehydrogenase catalytic domain-like
Adenosylhomocysteine is a competitive inhibitor of S-adenosyl-L-methionine-dependent methyl transferase reactions; therefore adenosylhomocysteinase may play a key role in the control of methylations via regulation of the intracellular concentration of adenosylhomocysteine.
Belongs to the adenosylhomocysteinase family.
Sar1p, Giardia homolog to GTP-binding protein Sar1p.
Involved in transport from the endoplasmic reticulum to the Golgi apparatus.
Belongs to the small GTPase superfamily. SAR1 family.
Probable GTP-binding protein that may be involved in cell development.
Belongs to the TRAFAC class dynamin-like GTPase superfamily. GB1/RHD3 GTPase family. RHD3 subfamily.
Zinc/RING finger domain, C3HC4 (zinc finger)
STRUCTURE-SPECIFIC ENDONUCLEASE SUBUNIT SLX1
Structure-specific endonuclease subunit SLX1 homolog
Catalytic subunit of a heterodimeric structure-specific endonuclease that resolves DNA secondary structures generated during DNA repair and recombination. Has endonuclease activity towards branched DNA substrates, introducing single-strand cuts in duplex DNA close to junctions with ss-DNA.
Forms a heterodimer with a member of the SLX4 family.
SUCCINATE--COA LIGASE [ADP/GDP-FORMING] SUBUNIT ALPHA, MITOCHONDRIAL
Succinate--CoA ligase [ADP-forming] subunit alpha-1, mitochondrial
Succinyl-CoA synthetase functions in the citric acid cycle (TCA), coupling the hydrolysis of succinyl-CoA to the synthesis of ATP and thus represents the only step of substrate-level phosphorylation in the TCA. The alpha subunit of the enzyme binds the substrates coenzyme A and phosphate, while succinate binding and nucleotide specificity is provided by the beta subunit.
Heterodimer of an alpha and a beta subunit.
Belongs to the succinate/malate CoA ligase alpha subunit family.
Succinate--CoA ligase [ADP-forming] subunit alpha-2, mitochondrial
Succinate--CoA ligase [ADP-forming] subunit alpha-3, mitochondrial
SUCCINATE--COA LIGASE [GDP-FORMING] SUBUNIT BETA, MITOCHONDRIAL
Succinate--CoA ligase [ADP-forming] subunit beta, hydrogenosomal
Succinyl-CoA synthetase functions in the citric acid cycle (TCA), coupling the hydrolysis of succinyl-CoA to the synthesis of ATP and thus represents the only step of substrate-level phosphorylation in the TCA. The beta subunit provides nucleotide specificity of the enzyme and binds the substrate succinate, while the binding sites for coenzyme A and phosphate are found in the alpha subunit.
Belongs to the succinate/malate CoA ligase beta subunit family.
Belongs to the class-I aminoacyl-tRNA synthetase family.
Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin.
Dimer of alpha and beta chains. A typical microtubule is a hollow water-filled tube with an outer diameter of 25 nm and an inner diameter of 15 nM. Alpha-beta heterodimers associate head-to-tail to form protofilaments running lengthwise along the microtubule wall with the beta-tubulin subunit facing the microtubule plus end conferring a structural polarity. Microtubules usually have 13 protofilaments but different protofilament numbers can be found in some organisms and specialized cells.
Triosephosphate isomerase is an extremely efficient metabolic enzyme that catalyzes the interconversion between dihydroxyacetone phosphate (DHAP) and D-glyceraldehyde-3-phosphate (G3P) in glycolysis and gluconeogenesis.
It is also responsible for the non-negligible production of methylglyoxal a reactive cytotoxic side-product that modifies and can alter proteins, DNA and lipids.
Belongs to the triosephosphate isomerase family.
Specifically methylates the N1 position of guanosine-37 in various cytoplasmic and mitochondrial tRNAs. Methylation is not dependent on the nature of the nucleoside 5' of the target nucleoside. This is the first step in the biosynthesis of wybutosine (yW), a modified base adjacent to the anticodon of tRNAs and required for accurate decoding.
Predominantly in the mitochondria and in the nucleus.
Belongs to the class I-like SAM-binding methyltransferase superfamily. TRM5/TYW2 family.
The active site is a redox-active disulfide bond.
Belongs to the class-II pyridine nucleotide-disulfide oxidoreductase family.
Belongs to the Giardia variant surface protein family.
Major surface-labeled trophozoite antigen 417
DEHYDRODOLICHYL DIPHOSPHATE SYNTHASE COMPLEX SUBUNIT DHDDS
DEHYDRODOLICHYL DIPHOSPHATE SYNTHASE FAMILY MEMBER
Di-trans,poly-cis-undecaprenyl-diphosphate synthase
Cis-prenyl transferase involved in the synthesis of dolichol, a long-chain polyprenol that is utilized as a sugar carrier in protein glycosylation in the endoplasmic reticulum (ER). Catalyzes the sequential condensation of isopentenyl pyrophosphate (IPP) with farnesyl pyrophosphate (FPP) to produce a polyprenyl pyrophosphate which contains 11 (major) and 12 (minor) isoprene units.
The synthetic pathway for dolichol synthesis is conserved in Giardia lamblia, even if some of the important enzymes are different from those of higher eukaryotes or remain unidentified.
RXG motif; crucial for prenyltransferase activity
O-glycosylated. The major glycan is a trisaccharide with Glc at the reducing terminus.
Uncharacterized 59.1 kDa protein in rpoA3 5'region