HPR (HPR1, At1g68010) encodes the peroxisomal NADH-dependent hydroxypyruvate reductase (glycerate dehydrogenase, EC 1.1.1.29), a member of the D-isomer specific 2-hydroxyacid dehydrogenase family. It reduces hydroxypyruvate, formed by serine:glyoxylate aminotransferase, to D-glycerate in the photorespiratory C2 cycle, oxidizing NADH supplied to the peroxisome by the malate shuttle. HPR1 carries a C-terminal microbody targeting signal and is found only in leaf peroxisomes. It is among the most abundant leaf peroxisomal matrix proteins and is expressed mainly in photosynthetic tissues, where it is induced by light. Knockout of HPR1 removes about 95% of leaf NADH-dependent hydroxypyruvate reductase activity. Growth defects in air are only mild, because cytosolic HPR2 and plastidic HPR3 provide bypass reactions, but hpr1 hpr2 double mutants are strongly air-sensitive. In germinating seeds lacking peroxisomal malate dehydrogenase, HPR1 can also reoxidize peroxisomal NADH to sustain fatty acid beta-oxidation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003729 mRNA binding | IDA PMID:32344669 Discovering the RNA-Binding Proteome of Plant Leaves with an... | MARK AS OVER ANNOTATED | Summary: HPR1 was recovered in a leaf RNA interactome capture (RIC) screen; the paper discusses metabolic enzymes in the leaf RBPome as putative moonlighting RNA binders. Reason: A proteome-wide crosslinking screen hit without follow-up on binding specificity or function; HPR1 is a peroxisomal matrix NAD-dependent dehydrogenase. mRNA binding is not an established function of the gene. Supporting Evidence: PMID:32344669 Moonlighting functions have been described for a number of metabolic enzymes across eukaryotes, including plants |
| GO:0005739 mitochondrion | HDA PMID:28887381 Global Analysis of Membrane-associated Protein Oligomerizati... | MARK AS OVER ANNOTATED | Summary: Detection in a leaf cell-fractionation / size-exclusion profiling study of membrane-associated protein complexes. Reason: HPR1 is a PTS1 protein that immunoelectron microscopy places exclusively in leaf peroxisomes; a single proteomics hit in a crude membrane fraction most likely reflects contamination by this abundant enzyme. Following projects/ARATH/organelle-audit.md rule 3, a single high-throughput hit for a protein localized elsewhere is marked over-annotated rather than removed. Supporting Evidence: PMID:28887381 Here we combined cell fractionation of Arabidopsis leaves with nondenaturing detergent solubilization and LC/MS-based profiling of size exclusion chromatography fractions PMID:9177031 Immunoelectron microscopy revealed that Arabidopsis HPR protein was exclusively localized in leaf peroxisomes in green leaves. |
| GO:0005777 peroxisome | HDA PMID:17951448 Proteome analysis of Arabidopsis leaf peroxisomes reveals no... | ACCEPT | Summary: HPR is among the most abundant matrix enzymes of isolated leaf peroxisomes. Reason: High-throughput evidence agreeing with immunoelectron microscopy; core location. Supporting Evidence: PMID:17951448 This pattern was most obvious for highly abundant matrix enzymes, namely GGT1, Ser-glyoxylate aminotransferase, HPR, and pMDH2 |
| GO:0005777 peroxisome | IDA PMID:12154131 Proteomic analysis of leaf peroxisomal proteins in greening ... | ACCEPT | Summary: Leaf peroxisome proteomics of greening cotyledons; HPR is named as one of the characterized leaf peroxisomal proteins. Reason: Consistent with immunoelectron microscopy and later peroxisome proteomics; core location. Supporting Evidence: PMID:12154131 only a few leaf peroxisomal proteins, that is hydroxypyruvate reductase (HPR), glycolate oxidase (GO) and alanine:glyoxylate aminotransferase 1 (AGT1), have been characterized |
| GO:0005777 peroxisome | IDA PMID:9177031 Hydroxypyruvate reductase with a carboxy-terminal targeting ... | ACCEPT | Summary: Immunoelectron microscopy localizes HPR exclusively to leaf peroxisomes. Reason: Direct localization evidence; core location of the HPR1 step. Supporting Evidence: PMID:9177031 Immunoelectron microscopy revealed that Arabidopsis HPR protein was exclusively localized in leaf peroxisomes in green leaves. |
| GO:0005777 peroxisome | IEA GO_REF:0000044 | ACCEPT | Summary: Mapping of the UniProt subcellular location (Peroxisome). Reason: Consistent with experimental localization. Supporting Evidence: PMID:9177031 Immunoelectron microscopy revealed that Arabidopsis HPR protein was exclusively localized in leaf peroxisomes in green leaves. |
| GO:0005829 cytosol | HDA PMID:25293756 A proteomic strategy for global analysis of plant protein co... | MARK AS OVER ANNOTATED | Summary: Detection in size-exclusion profiling of a crude cytosolic fraction of leaves. Reason: Peroxisomal matrix enzymes leak into crude cytosolic extracts when organelles break during homogenization. Immunoelectron microscopy places HPR1 exclusively in peroxisomes, and the Arabidopsis gene, unlike pumpkin HPR, is not alternatively spliced into a cytosolic form. The cytosolic hydroxypyruvate reductase bypass is carried out by the separate gene HPR2. Following projects/ARATH/organelle-audit.md rule 3, this single proteomics hit is marked over-annotated. The IBA row for the same term takes the same action. Supporting Evidence: PMID:25293756 Applying this approach to the crude cytosolic fraction of Arabidopsis thaliana leaves using size exclusion chromatography PMID:9177031 Immunoelectron microscopy revealed that Arabidopsis HPR protein was exclusively localized in leaf peroxisomes in green leaves. |
| GO:0005829 cytosol | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: PAINT inference of cytosolic activity from node PTN000107947, seeded by the E. coli glyoxylate/ hydroxypyruvate reductases GhrA and GhrB. Reason: The node's cytosolic location suits its bacterial donors and the cytosolic plant paralog HPR2, but HPR1 has acquired a C-terminal microbody targeting signal and is found exclusively in peroxisomes, so it has diverged in location from the ancestral state. Following projects/ARATH/organelle-audit.md rule 6 (one action per term group), this row takes the same MARK_AS_OVER_ANNOTATED action as the HDA cytosol row. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH FUNCTIONAL DIVERGENCE Sources checked: PANTHER:PTN000107947 · PTN000107947 SUPPORTS SOURCE BUT NOT TARGET The node's cytosolic location is seeded by the bacterial reductases GhrA (P75913) and GhrB (P37666), which have no organelles. HPR1 descends from the node but has a C-terminal microbody targeting signal and is found only in peroxisomes by immunoelectron microscopy, so the cytosolic location does not transfer to it. Supporting Evidence: PMID:9177031 Deduced amino acid sequences revealed that HPR in Arabidopsis contained the carboxy-terminal targeting signal to microbodies. PMID:9177031 Immunoelectron microscopy revealed that Arabidopsis HPR protein was exclusively localized in leaf peroxisomes in green leaves. |
| GO:0008266 poly(U) RNA binding | IDA PMID:17511964 Identification of proteins expressed at extremely low level ... | MARK AS OVER ANNOTATED | Summary: Leaf proteins retained on a poly(U)-affinity column and identified by 2-DE/MALDI-TOF; HPR was among them according to the full text (the cache holds the abstract only). Reason: The column was used deliberately to enrich proteins with nucleotide-binding motifs, so an NAD(H)-binding Rossmann-fold dehydrogenase is expected to be retained regardless of any RNA function. The method does not distinguish poly(U) RNA binding from cofactor-site affinity, and no RNA-related role of HPR1 is known. The observation is retained but is not a function of the gene. Supporting Evidence: PMID:17511964 Here we use a polyU-affinity column to enrich proteins with nucleotide-binding motifs. |
| GO:0008465 hydroxypyruvate reductase (NADH) activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference for the plant peroxisomal HPR clade, grounded in HPR1's own experimental data (HPR1 appears among its sources, as expected). Reason: Core molecular function. Supporting Evidence: PMID:22303256 In Arabidopsis, the peroxisomal reaction is catalyzed by HPR1 (At1g68010) using NADH as a co-factor |
| GO:0008465 hydroxypyruvate reductase (NADH) activity | IDA PMID:18952776 A cytosolic pathway for the conversion of hydroxypyruvate to... | ACCEPT | Summary: Recombinant HPR1 was assayed for hydroxypyruvate reduction alongside HPR2, and hpr1 knockouts retain only about 5% of leaf NADH-dependent HPR activity. Reason: Core molecular function, supported by enzyme assays and loss of activity in knockouts. Supporting Evidence: PMID:18952776 initial measurements indicated very low (∼5% of wild-type levels) NADH-dependent hydroxypyruvate reductase activity in leaf extracts of both lines. PMID:21205613 most of which is subsequently reduced to glycerate by the NADH-dependent peroxisomal enzyme HP reductase (HPR1) |
| GO:0008465 hydroxypyruvate reductase (NADH) activity | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic mapping from EC 1.1.1.29 / RHEA:17905. Reason: Consistent with the experimentally established core activity. Supporting Evidence: file:ARATH/HPR/HPR-uniprot.txt Catalyzes the NADH-dependent reduction of hydroxypyruvate into glycerate in the photorespiratory core cycle. |
| GO:0008465 hydroxypyruvate reductase (NADH) activity | NAS PMID:12154131 Proteomic analysis of leaf peroxisomal proteins in greening ... | ACCEPT | Summary: Author statement in the leaf peroxisome proteomics paper naming HPR as a characterized peroxisomal enzyme. Reason: Consistent with the experimental data; core activity. Supporting Evidence: PMID:12154131 only a few leaf peroxisomal proteins, that is hydroxypyruvate reductase (HPR), glycolate oxidase (GO) and alanine:glyoxylate aminotransferase 1 (AGT1), have been characterized |
| GO:0009507 chloroplast | HDA PMID:18431481 Sorting signals, N-terminal modifications and abundance of t... | MARK AS OVER ANNOTATED | Summary: Identification in a large-scale MS analysis of isolated chloroplast preparations. Reason: HPR1 has no transit peptide and is exclusively peroxisomal by immunoelectron microscopy. Peroxisomes co-purify with chloroplasts, and the study discusses contaminants in its preparations. Following projects/ARATH/organelle-audit.md rule 3, this single proteomics hit is marked over-annotated rather than removed. Supporting Evidence: PMID:18431481 This quantitative information was used to determine possible biases for protein targeting prediction by TargetP and also to understand the significance of protein contaminants. PMID:9177031 Immunoelectron microscopy revealed that Arabidopsis HPR protein was exclusively localized in leaf peroxisomes in green leaves. |
| GO:0009853 photorespiration | TAS PMID:9177031 Hydroxypyruvate reductase with a carboxy-terminal targeting ... | ACCEPT | Summary: HPR1 catalyses the peroxisomal reduction of hydroxypyruvate to glycerate in photorespiration. Reason: Core process. Mutant analyses show that HPR1 carries most photorespiratory hydroxypyruvate flux, although the cytosolic HPR2 bypass hides this in single mutants grown in air. Supporting Evidence: PMID:9177031 Five Arabidopsis EST cDNA clones of hydroxypyruvate reductase (HPR), a photorespiratory enzyme in leaf peroxisomes, were sequenced. PMID:18952776 showing that HPR1 plays the dominant role in photorespiration |
| GO:0009854 oxidative photosynthetic carbon pathway | IEA GO_REF:0000041 | ACCEPT | Summary: UniPathway mapping (photorespiration; 3-phospho-D-glycerate from glycine) to the C2-cycle term, a child of photorespiration. Reason: Correct and specific (GO:0009854 is part_of GO:0009853); the HPR1 reaction is a step of the C2 cycle. The core function nonetheless uses the broader GO:0009853 photorespiration, so that every C2-cycle step and ammonia refixation share one process term (see modules/photorespiration_c2_cycle.yaml). Supporting Evidence: PMID:22303256 In Arabidopsis, the peroxisomal reaction is catalyzed by HPR1 (At1g68010) using NADH as a co-factor |
| GO:0009854 oxidative photosynthetic carbon pathway | IMP PMID:18952776 A cytosolic pathway for the conversion of hydroxypyruvate to... | ACCEPT | Summary: hpr1 knockouts accumulate labelled hydroxypyruvate and have altered photorespiratory gas exchange; hpr1 hpr2 double knockouts are air-sensitive. Reason: Genetic evidence that HPR1 operates in the photorespiratory C2 cycle, as the dominant but not sole hydroxypyruvate reductase. Supporting Evidence: PMID:18952776 The combined deletion of both HPR1 and HPR2, however, results in distinct air-sensitivity and a dramatic reduction in photosynthetic performance. PMID:18952776 showing that HPR1 plays the dominant role in photorespiration |
| GO:0016616 oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor | IEA GO_REF:0000120 | MODIFY | Summary: Mapping from the D-isomer 2-hydroxyacid dehydrogenase catalytic domain signature. Reason: Correct but general; the specific, experimentally supported activity is hydroxypyruvate reductase (NADH) activity (GO:0008465), which the gene already carries. Proposed replacements: hydroxypyruvate reductase (NADH) activity Supporting Evidence: file:ARATH/HPR/HPR-uniprot.txt IPR006139; D-isomer_2_OHA_DH_cat_dom PMID:22303256 In Arabidopsis, the peroxisomal reaction is catalyzed by HPR1 (At1g68010) using NADH as a co-factor |
| GO:0030267 glyoxylate reductase (NADPH) activity | IBA GO_REF:0000033 | UNDECIDED | Summary: PAINT inference of NADPH-dependent glyoxylate reductase activity from the glyoxylate/hydroxypyruvate reductase node PTN000107947 (donors include Arabidopsis HPR2 and HPR3, E. coli GhrA/GhrB and human GRHPR). Reason: HPR1 descends from the node, and HPR1 is said to have relaxed substrate and cofactor specificity. However, it is characterized as an NADH-dependent hydroxypyruvate reductase, and the cached sources give no HPR1 rates for NADPH with glyoxylate (the Table 1 values are not in the cached text). It cannot be decided here whether HPR1 kept or lost a physiologically meaningful NADPH-glyoxylate reductase activity. Propagation Review Root cause: UNRESOLVED Failure modes: FUNCTIONAL DIVERGENCE Sources checked: PANTHER:PTN000107947 · PTN000107947 UNRESOLVED The node is supported by NADPH-preferring glyoxylate/hydroxypyruvate reductases (Arabidopsis HPR2 and HPR3, E. coli GhrA/GhrB, human GRHPR). HPR1 belongs to the peroxisomal, NADH-preferring branch. The cached sources do not report its NADPH-glyoxylate kinetics, so retention or loss of this activity cannot be judged. Supporting Evidence: PMID:18952776 This broad-range effect was to be expected due to the relaxed substrate and cofactor specificities of HPR1 and, even more so, of HPR2 |
| GO:0042631 cellular response to water deprivation | IEP PMID:19529821 Shoot-specific down-regulation of protein farnesyltransferas... | KEEP AS NON CORE | Summary: Northern blots show a transient, about two-fold induction of AtHPR1 transcripts in leaves during drought. Reason: A valid expression-pattern observation, which motivated use of the HPR1 promoter as a drought-inducible, shoot-specific promoter. It reflects transcriptional regulation and is peripheral to the enzymatic function. Supporting Evidence: PMID:19529821 This suggests the AtHPR expression is up-regulated by drought |
| GO:0048046 apoplast | HDA PMID:18538804 Hydroponic isotope labelling of entire plants (HILEP) for qu... | MARK AS OVER ANNOTATED | Summary: Detection in an apoplast-focused quantitative proteomics study under oxidative stress. Reason: HPR1 has no secretory signal peptide and is exclusively peroxisomal by immunoelectron microscopy; detection in apoplastic extracts reflects leakage of abundant intracellular proteins. Following projects/ARATH/organelle-audit.md rule 3, this single proteomics hit is marked over-annotated. Supporting Evidence: PMID:18538804 it was possible to show differential protein expression in the apoplast of plants submitted to oxidative stress PMID:9177031 Immunoelectron microscopy revealed that Arabidopsis HPR protein was exclusively localized in leaf peroxisomes in green leaves. |
| GO:0051287 NAD binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO mapping from the NAD-binding domain of D-isomer 2-hydroxyacid dehydrogenases. Reason: HPR1 uses NADH as its cofactor; NAD binding is part of the catalytic mechanism of the core activity. Supporting Evidence: file:ARATH/HPR/HPR-uniprot.txt IPR006140; D-isomer_DH_NAD-bd PMID:22303256 In Arabidopsis, the peroxisomal reaction is catalyzed by HPR1 (At1g68010) using NADH as a co-factor |
| GO:0071482 cellular response to light stimulus | IEP PMID:19529821 Shoot-specific down-regulation of protein farnesyltransferas... | KEEP AS NON CORE | Summary: Light induction of AtHPR1 transcripts, discussed in the paper from published expression datasets. Reason: Light regulation of HPR1 expression is consistent with its photorespiratory role and with co-regulation of photorespiratory genes. As an expression response, it is peripheral to the enzymatic function. Supporting Evidence: PMID:19529821 AtHPR1 expression was induced between 1.5 and 3.5-fold by blue, far red, red, UV-A, UV-AB, and white light PMID:22303256 The Hpr 1 gene shows similar regulatory properties like Sgat with positive light regulation and repression under low nitrogen conditions |
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Download this section (compressed HTML)Q: Does HPR1 have a physiologically relevant NADPH- or NADH-dependent glyoxylate reductase activity, as implied by its family placement, or is it specific for hydroxypyruvate in vivo?
Q: Under which light and temperature conditions does flux through the cytosolic HPR2 bypass become significant relative to peroxisomal HPR1?
Experiment: Determine full steady-state kinetics of purified recombinant HPR1 with hydroxypyruvate and glyoxylate using NADH and NADPH, and test whether hpr1 leaves accumulate glyoxylate or glycolate under high photorespiratory flux.
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