Affinage

ASPA

Aspartoacylase · UniProt P45381

Round 2 corrected
Length
313 aa
Mass
35.7 kDa
Annotated
2026-04-28
130 papers in source corpus 14 papers cited in narrative 14 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ASPA (aspartoacylase) is a zinc metalloenzyme that hydrolyzes N-acetyl-L-aspartate (NAA) to aspartate and acetate, providing acetyl groups essential for myelin lipid synthesis in the central nervous system (PMID:3116332, PMID:9407392). Structurally, ASPA comprises an N-terminal catalytic domain with a carboxypeptidase A-like zinc-dependent hydrolase fold and a C-terminal domain that gates substrate access to the active site; catalysis depends on zinc-coordinating residues (H21, E24, H116), a proton donor (E178), and substrate-binding arginines (R63, R71), and glycosylation is required for full stability and activity (PMID:17194761, PMID:17391648, PMID:16669630). ASPA functions as an active monomer in both the cytoplasm and nucleus of oligodendrocytes, with evidence for active or facilitated nuclear import (PMID:16935940). Loss-of-function mutations in ASPA cause Canavan disease, an autosomal recessive leukodystrophy characterized by NAA accumulation and dysmyelination (PMID:3116332, PMID:8252036).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1987 High

    Identifying the enzymatic basis of Canavan disease established that ASPA catalyzes NAA hydrolysis and that its deficiency leads to NAA accumulation and dysmyelination, framing the gene's central biological role.

    Evidence Enzymatic activity assay in patient fibroblasts showing absent aspartoacylase activity

    PMID:3116332

    Open questions at the time
    • Molecular identity (gene/cDNA) of ASPA not yet determined
    • Catalytic mechanism unknown
    • Tissue and subcellular distribution of activity uncharacterized
  2. 1993 High

    Cloning the ASPA cDNA and demonstrating recombinant enzymatic activity enabled molecular characterization of disease-causing mutations and first implicated specific residues (including E285) in catalysis.

    Evidence cDNA cloning with heterologous expression in bacteria; identification of E285A as the predominant Ashkenazi Jewish mutation

    PMID:8252036

    Open questions at the time
    • Catalytic mechanism and active-site architecture unresolved
    • Three-dimensional structure unavailable
  3. 1994 High

    Systematic in vitro expression of patient-derived mutations (Y231X, E285A, A305E) quantified residual activity and demonstrated allelic heterogeneity, while genomic characterization mapped ASPA to 17p13-ter across six exons.

    Evidence In vitro mutagenesis and expression with quantitative enzyme assays; FISH and somatic cell hybrid mapping

    PMID:8023850 PMID:8088831

    Open questions at the time
    • Structure-function relationships for most residues unknown
    • No structural data to explain why specific mutations abolish activity
  4. 1996 High

    Expanding the mutation spectrum across diverse ethnic backgrounds (including I16T, G27R, D114E, G123E, C152Y, R168C) and confirming loss of function by COS-7 expression demonstrated that pathogenic variants are distributed across the entire protein, not confined to a single domain.

    Evidence Site-directed mutagenesis with transient expression in COS-7 cells and enzyme activity assay

    PMID:12638939 PMID:7668285 PMID:8659549

    Open questions at the time
    • Active-site residue identity still inferred from sequence homology rather than structure
    • Role of glycosylation and metal cofactors unknown
  5. 1997 Medium

    Metabolic flux analysis revealed that ASPA deficiency eliminates intercompartmental NAA-to-aspartate cycling, creating a large daily aspartate deficit and depriving oligodendrocytes of acetyl groups for myelin lipid synthesis — connecting the enzymatic defect to the dysmyelination phenotype.

    Evidence Quantitative biochemical flux modeling using multi-species NAA metabolite data and Canavan disease metabolite profiles

    PMID:9407392

    Open questions at the time
    • Flux estimates rely on modeling rather than direct in vivo tracing
    • Relative contribution of acetyl-group deficit vs. NAA toxicity to pathology not resolved
  6. 2003 High

    Recombinant kinetic characterization showed relaxed acyl-group specificity and confirmed that E285A drastically reduces both stability and activity while the conservative E285D retains partial function, pinpointing E285 as catalytically essential.

    Evidence Recombinant E. coli expression with continuous spectrophotometric kinetic assays and site-directed mutagenesis

    PMID:12706335

    Open questions at the time
    • Structural basis of E285 contribution awaited crystallographic data
    • Substrate-binding mode unresolved
  7. 2006 High

    Crystal structures of human and rat ASPA revealed a two-domain architecture — an N-terminal carboxypeptidase A-like zinc hydrolase domain and a C-terminal domain that occludes the active site from polypeptide substrates — explaining the enzyme's specificity for small-molecule NAA and identifying the zinc coordination sphere and a putative substrate-gating loop (residues 158–164).

    Evidence X-ray crystallography at 2.8 Å (human) and 1.8 Å (rat) resolution

    PMID:17194761

    Open questions at the time
    • No substrate- or product-bound co-crystal structure
    • Gating dynamics of residues 158–164 not experimentally validated
  8. 2006 High

    Demonstrating that ASPA is glycosylated, contains one zinc per subunit with chelation-reversible activity loss, and functions as a monomer in both cytoplasm and nucleus of oligodendrocytes established key biochemical properties and an unexpected nuclear localization with enzymatic activity.

    Evidence Pichia pastoris expression with mass spectrometry (glycan), zinc chelation/reconstitution, subcellular fractionation with activity assay, size-exclusion chromatography, GFP-fusion localization in COS-7 cells

    PMID:16669630 PMID:16935940

    Open questions at the time
    • Nuclear import mechanism (signal sequence or carrier) not identified
    • Biological role of nuclear NAA hydrolysis unknown
  9. 2007 High

    Comprehensive site-directed mutagenesis of predicted active-site residues (H21, E24, H116 for zinc coordination; E178 as proton donor; R63, R71 for substrate binding; C124/C152 for disulfide stability) definitively assigned catalytic roles, confirming ASPA belongs to the carboxypeptidase A metalloenzyme family.

    Evidence Homology model-guided mutagenesis with transient expression, Western blot protein-level controls, and quantitative enzyme activity assay

    PMID:17391648

    Open questions at the time
    • No substrate-bound crystal structure to confirm predicted binding geometry
    • Transition-state stabilization by R63 inferred from analogy, not directly visualized

Open questions

Synthesis pass · forward-looking unresolved questions
  • The biological function of nuclear ASPA, the structural basis of substrate gating by the C-terminal domain, and the relative contributions of NAA toxicity versus acetyl-group deprivation to Canavan disease pathogenesis remain unresolved.
  • No substrate- or transition-state-bound co-crystal structure available
  • Nuclear import mechanism and nuclear NAA metabolic function uncharacterized
  • In vivo metabolic tracing to distinguish NAA toxicity from acetyl-group deficit not performed

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 6
Localization
GO:0005634 nucleus 1 GO:0005829 cytosol 1
Pathway
R-HSA-1430728 Metabolism 3

Evidence

Reading pass · 14 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1987 Aspartoacylase (ASPA) deficiency was identified as the cause of elevated N-acetylaspartate (NAA) excretion and leukodystrophy; fibroblasts from the patient showed absent aspartoacylase activity, establishing that ASPA catalyzes NAA hydrolysis in brain and that its deficiency leads to dysmyelination. Enzymatic activity assay in patient fibroblasts; CSF/plasma NAA ratio measurement Journal of inherited metabolic disease High 3116332
1993 The human aspartoacylase (ASPA) cDNA was cloned and shown to express aspartoacylase activity in bacteria. A common missense mutation Glu285Ala (854A→C) was identified in 85% of Canavan alleles and predicted to disrupt a catalytic Ser/His/Glu triad, establishing that the catalytic domain involves these residues. cDNA cloning, heterologous expression in bacteria, mutation analysis of patient alleles Nature genetics High 8252036
1994 The human ASPA gene was mapped to chromosome 17p13-ter, spans 29 kb with 6 exons and 5 introns, and its coding sequences cross-hybridize with genomic DNA from multiple vertebrates, indicating evolutionary conservation of aspartoacylase. Genomic cloning, Southern blot analysis of somatic cell hybrid lines, fluorescence in situ hybridization (FISH) Genomics High 8088831
1994 Three point mutations in ASPA (693C→A causing Tyr231→stop, 854A→C causing Glu285→Ala, 914C→A causing Ala305→Glu) were characterized by in vitro expression: Tyr231→stop and Ala305→Glu cause complete loss of ASPA activity, while Glu285→Ala retains ~2.5% activity. A splice-site mutation (433−2 A→G) causing exon 3 skipping and frameshift was also identified. In vitro expression of mutant cDNAs in cell-free or cellular systems, enzyme activity assay American journal of human genetics High 8023850
1995 Nine ASPA mutations in non-Jewish Canavan patients were identified; A305E is the predominant pan-European mutation (39.5% of alleles), and in vitro expression studies confirmed these mutations cause loss of aspartoacylase enzymatic activity. Mutation analysis of ASPA gene, in vitro expression, enzyme activity assay American journal of human genetics High 7668285
1996 Eight novel ASPA missense and deletion mutations in non-Jewish Canavan patients (including I16T, G27R, D114E, G123E, C152Y, R168C, 32ΔT, 876ΔAGAA) were introduced into wild-type cDNA by PCR mutagenesis; in vitro expression in COS-7 cells confirmed all lead to ASPA enzyme deficiency. Site-directed mutagenesis, transient expression in COS-7 cells, enzyme activity assay American journal of human genetics High 8659549
1997 Analysis of NAA biochemistry in Canavan disease established that ASPA deficiency creates a daily aspartate deficit in the CNS at least six times the static free-aspartate level, eliminates the intercompartmental NAA-to-aspartate cycling that normally supplies acetyl groups for myelin lipid synthesis, and results in up to 50-fold reduction in the intercompartmental NAA gradient. Biochemical flux analysis of NAA cycle across multiple vertebrate species and Canavan disease metabolite data Journal of molecular neuroscience Medium 9407392
2002 Fourteen novel ASPA mutations in non-Jewish patients were identified; in vitro expression in COS-7 cells and patient fibroblast assays confirmed enzyme deficiency. Notably, E24G disrupts the first esterase catalytic domain consensus sequence, reinforcing the importance of Glu24 for catalysis; IVS1−2A→T caused retention of 40 nt of intron 1. ASPA gene sequencing, transient expression in COS-7 cells, enzyme activity assay in fibroblasts Journal of inherited metabolic disease High 12638939
2002 AAV-2 vector-mediated delivery of the ASPA gene directly to human brain in Canavan disease patients demonstrated the first clinical use of AAV in the human brain, providing proof-of-concept that ASPA can be delivered in vivo to correct the enzymatic deficiency. Clinical gene therapy protocol; neurosurgical AAV-2 delivery; pre/post neurological, biochemical, and radiological assessment Human gene therapy Medium 12162821
2003 Murine and human aspartoacylase were cloned and expressed in E. coli. Kinetic parameters showed relaxed substrate specificity for the acyl group. The clinically relevant E285A mutant has markedly reduced stability and barely detectable activity, while E285D retains ~one-fifth normal activity, establishing that Glu285 is critical for catalysis. Recombinant expression in E. coli, enzyme-coupled continuous spectrophotometric kinetic assay, site-directed mutagenesis Archives of biochemistry and biophysics High 12706335
2006 Crystal structures of human (2.8 Å) and rat (1.8 Å) aspartoacylase revealed that the N-terminal domain adopts a zinc-dependent hydrolase fold related to carboxypeptidase A, with a catalytic zinc ion coordinated by specific residues. The C-terminal domain (~100 residues) forms a globular domain that wraps around the N-terminal domain and occludes the active-site channel from polypeptide substrates. Residues 158–164 may gate substrate access. The catalytic mechanism is proposed to be analogous to carboxypeptidases. X-ray crystallography of recombinant human and rat ASPA; structural comparison with carboxypeptidase A Proceedings of the National Academy of Sciences of the United States of America High 17194761
2006 Human aspartoacylase expressed in Pichia pastoris is 150-fold more active and significantly more stable than the E. coli-expressed form. Mass spectrometry showed the enzyme contains a glycosylation modification; deglycosylation or mutation at the glycosylation site decreases stability and catalytic activity. Each subunit contains one zinc atom; chelation causes reversible loss of activity, establishing ASPA as a zinc metalloenzyme. Pichia pastoris expression, mass spectrometry of glycan, zinc chelation studies, kinetic assays Biochemistry High 16669630
2006 Aspartoacylase localizes not only to the cytoplasm but also to the nucleus of rat brain cells, kidney, and cultured oligodendrocytes. Subcellular fractionation showed low but detectable NAA-hydrolyzing activity in nuclear fractions. Size-exclusion chromatography showed ASPA is an active monomer in both compartments (not a dimer). A GFP-hASPA fusion protein exceeding the nuclear pore size limit also showed nuclear distribution, suggesting active or facilitated nuclear import. Immunohistochemistry, subcellular fractionation with enzyme activity assay, size-exclusion chromatography, GFP fusion protein expression in COS-7 cells FASEB journal High 16935940
2007 Homology modeling of ASPA based on carboxypeptidase A guided site-directed mutagenesis. Mutations of putative zinc-binding residues (H21G, E24D/G, H116G), the proposed proton donor (E178A), substrate carboxyl-binding residue (R71N), and transition-state stabilizing residue (R63N) all yield wild-type ASPA protein levels but undetectable activity. Double-swap mutants (H21E/E24H and E24H/H116E) also abolish activity. Cys124 and Cys152 alanine substitutions reduce both protein and activity levels, suggesting a disulfide bond. These results confirm ASPA belongs to the carboxypeptidase A family and define key catalytic residues. Homology modeling, site-directed mutagenesis, transient expression, Western blotting, enzyme activity assay Brain research High 17391648

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Towards a proteome-scale map of the human protein-protein interaction network. Nature 2090 16189514
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
1999 Identification of a novel aspartic protease (Asp 2) as beta-secretase. Molecular and cellular neurosciences 938 10656250
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2015 Widespread macromolecular interaction perturbations in human genetic disorders. Cell 454 25910212
1988 Cell attachment to thrombospondin: the role of ARG-GLY-ASP, calcium, and integrin receptors. The Journal of cell biology 450 2848850
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2008 Unconventional serine proteases: variations on the catalytic Ser/His/Asp triad configuration. Protein science : a publication of the Protein Society 241 18824507
1992 Regulated expression on human macrophages of endoglin, an Arg-Gly-Asp-containing surface antigen. European journal of immunology 212 1537377
2002 Clinical protocol. Gene therapy of Canavan disease: AAV-2 vector for neurosurgical delivery of aspartoacylase gene (ASPA) to the human brain. Human gene therapy 193 12162821
1993 Cloning of the human aspartoacylase cDNA and a common missense mutation in Canavan disease. Nature genetics 177 8252036
1998 His-Asp phosphotransfer signal transduction. Journal of biochemistry 174 9538242
1995 Structure and function of ASP, the human homolog of the mouse agouti gene. Human molecular genetics 159 7757071
1999 Synthesis of aspartyl-tRNA(Asp) in Escherichia coli--a snapshot of the second step. The EMBO journal 154 10562565
1999 Abnormal spindle protein, Asp, and the integrity of mitotic centrosomal microtubule organizing centers. Science (New York, N.Y.) 141 10073938
2008 Human DNMT2 methylates tRNA(Asp) molecules using a DNA methyltransferase-like catalytic mechanism. RNA (New York, N.Y.) 140 18567810
2005 RNA SHAPE chemistry reveals nonhierarchical interactions dominate equilibrium structural transitions in tRNA(Asp) transcripts. Journal of the American Chemical Society 131 15796531
2001 The drosophila protein asp is involved in microtubule organization during spindle formation and cytokinesis. The Journal of cell biology 131 11352927
2013 Proteomic analysis of podocyte exosome-enriched fraction from normal human urine. Journal of proteomics 126 23376485
1998 Coordinated release of acylation stimulating protein (ASP) and triacylglycerol clearance by human adipose tissue in vivo in the postprandial period. Journal of lipid research 121 9555951
2007 Toward a confocal subcellular atlas of the human proteome. Molecular & cellular proteomics : MCP 114 18029348
2001 Polo kinase and Asp are needed to promote the mitotic organizing activity of centrosomes. Nature cell biology 109 11283617
1994 Canavan disease: mutations among Jewish and non-Jewish patients. American journal of human genetics 108 8023850
2000 Possible His to Asp phosphorelay signaling in an Arabidopsis two-component system. FEBS letters 106 10930573
1991 An Arg-Gly-Asp sequence within thrombin promotes endothelial cell adhesion. The Journal of cell biology 102 1988465
1993 A homoallelic Gly317-->Asp mutation in ALPL causes the perinatal (lethal) form of hypophosphatasia in Canadian mennonites. Genomics 100 8406453
1987 N-acetylaspartic aciduria due to aspartoacylase deficiency--a new aetiology of childhood leukodystrophy. Journal of inherited metabolic disease 95 3116332
1999 Acylation stimulating protein (ASP), an adipocyte autocrine: new directions. Seminars in cell & developmental biology 91 10355026
2002 Acylation-stimulating protein (ASP) deficiency induces obesity resistance and increased energy expenditure in ob/ob mice. The Journal of biological chemistry 83 12244109
2005 Spindle pole organization in Drosophila S2 cells by dynein, abnormal spindle protein (Asp), and KLP10A. Molecular biology of the cell 80 15888542
2020 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains. Cell reports 79 32814053
2013 The microcephaly protein Asp regulates neuroepithelium morphogenesis by controlling the spatial distribution of myosin II. Nature cell biology 78 24142104
2010 Human variation in alcohol response is influenced by variation in neuronal signaling genes. Alcoholism, clinical and experimental research 74 20201926
1992 The Ser-Arg-Tyr-Asp region of the major surface glycoprotein of Leishmania mimics the Arg-Gly-Asp-Ser cell attachment region of fibronectin. The Journal of biological chemistry 73 1629196
1997 Acylation-stimulating protein (ASP) regulates glucose transport in the rat L6 muscle cell line. Biochimica et biophysica acta 70 9059512
1998 His...Asp catalytic dyad of ribonuclease A: structure and function of the wild-type, D121N, and D121A enzymes. Biochemistry 68 9636030
2015 A tonoplast Glu/Asp/GABA exchanger that affects tomato fruit amino acid composition. The Plant journal : for cell and molecular biology 67 25602029
2001 STAT3 activation is required for Asp(816) mutant c-Kit induced tumorigenicity. Oncogene 66 11494148
1999 Acylation stimulating protein (ASP) deficiency alters postprandial and adipose tissue metabolism in male mice. The Journal of biological chemistry 64 10593909
2009 Septins AspA and AspC are important for normal development and limit the emergence of new growth foci in the multicellular fungus Aspergillus nidulans. Eukaryotic cell 63 19949047
1999 Mice lacking acylation stimulating protein (ASP) have delayed postprandial triglyceride clearance. Journal of lipid research 58 10484614
1990 Site-directed mutagenesis of the conserved Asp-443 and Asp-498 carboxy-terminal residues of HIV-1 reverse transcriptase. Nucleic acids research 56 1699202
2012 Anti-diabetic activities of Acanthopanax senticosus polysaccharide (ASP) in combination with metformin. International journal of biological macromolecules 55 22326821
2006 Structure of aspartoacylase, the brain enzyme impaired in Canavan disease. Proceedings of the National Academy of Sciences of the United States of America 55 17194761
2000 Cleavage of the actin-capping protein alpha -adducin at Asp-Asp-Ser-Asp633-Ala by caspase-3 is preceded by its phosphorylation on serine 726 in cisplatin-induced apoptosis of renal epithelial cells. The Journal of biological chemistry 55 10823823
2002 Identification and characterization of novel mutations of the aspartoacylase gene in non-Jewish patients with Canavan disease. Journal of inherited metabolic disease 52 12638939
2006 Identification of an essential gene responsible for D-Asp incorporation in the Lactococcus lactis peptidoglycan crossbridge. Molecular microbiology 51 17083466
1991 Locations of Arg-82, Asp-85, and Asp-96 in helix C of bacteriorhodopsin relative to the aqueous boundaries. Proceedings of the National Academy of Sciences of the United States of America 50 1656452
1997 Canavan disease. Analysis of the nature of the metabolic lesions responsible for development of the observed clinical symptoms. Journal of molecular neuroscience : MN 48 9407392
1996 Roles of Glu 349 and Asp 352 in membrane insertion and translocation by diphtheria toxin. Protein science : a publication of the Protein Society 48 8845758
1995 The molecular basis of canavan (aspartoacylase deficiency) disease in European non-Jewish patients. American journal of human genetics 48 7668285
1994 Canavan disease: genomic organization and localization of human ASPA to 17p13-ter and conservation of the ASPA gene during evolution. Genomics 47 8088831
1996 Identification and expression of eight novel mutations among non-Jewish patients with Canavan disease. American journal of human genetics 46 8659549
2006 Aspartoacylase is a regulated nuclear-cytoplasmic enzyme. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 45 16935940
2002 Catalytic mechanism of S-adenosylhomocysteine hydrolase. Site-directed mutagenesis of Asp-130, Lys-185, Asp-189, and Asn-190. The Journal of biological chemistry 45 11927587
1993 Antiapoptotic effect of heterozygously expressed mutant RI (Ala336-->Asp) subunit of cAMP kinase I in a rat leukemia cell line. The Journal of biological chemistry 45 8385140
2012 A genome-wide association study provides evidence for association of chromosome 8p23 (MYP10) and 10q21.1 (MYP15) with high myopia in the French Population. Investigative ophthalmology & visual science 44 23049088
1994 Site-directed mutagenesis of the Asp-197 and Asp-202 residues in chitinase A1 of Bacillus circulans WL-12. Bioscience, biotechnology, and biochemistry 44 7765724
2011 Streptococcus pyogenes antigen I/II-family polypeptide AspA shows differential ligand-binding properties and mediates biofilm formation. Molecular microbiology 43 21736640
2023 Exploring Kinase Asp-Phe-Gly (DFG) Loop Conformational Stability with AlphaFold2-RAVE. Journal of chemical information and modeling 41 37981824
2009 Recombinant C3adesArg/acylation stimulating protein (ASP) is highly bioactive: a critical evaluation of C5L2 binding and 3T3-L1 adipocyte activation. Molecular immunology 41 19767107
2004 Canavan disease: carrier-frequency determination in the Ashkenazi Jewish population and development of a novel molecular diagnostic assay. American journal of medical genetics. Part A 41 14699612
2003 A single amino acid change (Asp 53 --> Ala53) converts Survivin from anti-apoptotic to pro-apoptotic. Molecular biology of the cell 41 14699067
2007 C-kit Asp-816-Val mutation analysis in patients with mastocytosis. Dermatology (Basel, Switzerland) 40 17191042
2015 Microcephaly protein Asp focuses the minus ends of spindle microtubules at the pole and within the spindle. The Journal of cell biology 38 26644514
2014 Extracellular-matrix-based and Arg-Gly-Asp-modified photopolymerizing hydrogels for cartilage tissue engineering. Tissue engineering. Part A 37 25266634
2006 Characterization of human aspartoacylase: the brain enzyme responsible for Canavan disease. Biochemistry 35 16669630
2000 His-Asp phosphorelay signaling: a communication avenue between plants and their environment. Plant molecular biology 35 10794527
2006 Mild-onset presentation of Canavan's disease associated with novel G212A point mutation in aspartoacylase gene. Annals of neurology 34 16437572
2004 Increased cell death after therapy with an Arg-Gly-Asp-linked somatostatin analog. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 34 15471839
2015 The HIV-1 antisense protein (ASP) induces CD8 T cell responses during chronic infection. Retrovirology 33 25809376
2015 An Asp-CaM complex is required for centrosome-pole cohesion and centrosome inheritance in neural stem cells. The Journal of cell biology 32 26620907
2008 Carrier frequency of autosomal-recessive disorders in the Ashkenazi Jewish population: should the rationale for mutation choice for screening be reevaluated? Prenatal diagnosis 32 18264947
2003 Purification and preliminary characterization of brain aspartoacylase. Archives of biochemistry and biophysics 32 12706335
1998 Plasma acylation stimulating protein (ASP) as a predictor of impaired cellular biological response to ASP in patients with hyperapoB. European journal of clinical investigation 32 9767372
1998 Inhibition of integrin signaling with Arg-Gly-Asp motifs in rat hepatic stellate cells. Journal of hepatology 32 9833913
1998 Immunodominant peptide epitopes of allergen, Asp f 1 from the fungus Aspergillus fumigatus. Peptides 32 9864052
1994 The adipsin-ASP pathway and regulation of adipocyte function. Annals of medicine 32 7695862
2007 Mutational analysis of aspartoacylase: implications for Canavan disease. Brain research 31 17391648
2001 Involvement of the Arg-Asp-His catalytic triad in enzymatic cleavage of the phosphodiester bond. Biochemistry 31 11331006
2000 Mutation detection in the aspartoacylase gene in 17 patients with Canavan disease: four new mutations in the non-Jewish population. European journal of human genetics : EJHG 31 10909858
2013 Elevated fetal adipsin/acylation-stimulating protein (ASP) in obese pregnancy: novel placental secretion via Hofbauer cells. The Journal of clinical endocrinology and metabolism 30 23956345
2005 Glu-Q-tRNA(Asp) synthetase coded by the yadB gene, a new paralog of aminoacyl-tRNA synthetase that glutamylates tRNA(Asp) anticodon. Biochimie 30 16164993
2011 Truncation of murine CaV1.2 at Asp-1904 results in heart failure after birth. The Journal of biological chemistry 29 21832054
2002 The role of Asp-462 in regulating Akt activity. The Journal of biological chemistry 29 12124386
2010 Influence of Lβ-, Dα- and Dβ-Asp isomers of the Asp-76 residue on the properties of αA-crystallin 70-88 peptide. Amino acids 28 20437187
2016 Inhibitors of Arg-Gly-Asp-Binding Integrins Reduce Development of Pancreatic Fibrosis in Mice. Cellular and molecular gastroenterology and hepatology 27 28174730
2001 Acylation stimulating protein (ASP) acute effects on postprandial lipemia and food intake in rodents. International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity 26 11360154
2007 The ASP receptor C5L2 is regulated by metabolic hormones associated with insulin resistance. Biochemistry and cell biology = Biochimie et biologie cellulaire 25 17464341
1999 [Cytotoxic activity and cytokine gene induction of Asp-hemolysin to murine macrophages]. Nihon Ishinkin Gakkai zasshi = Japanese journal of medical mycology 25 10536308
2000 High sensitivity bioassay of paralytic (PSP) and amnesic (ASP) algal toxins based on the fluorimetric detection of [Ca(2+)](i) in rat cortical primary cultures. Toxicon : official journal of the International Society on Toxinology 24 10736481
1996 Perturbed interaction between residues 85 and 204 in Tyr-185-->Phe and Asp-85-->Glu bacteriorhodopsins. Biophysical journal 24 8968608
1985 The structure of yeast tRNA(Asp). A model for tRNA interacting with messenger RNA. Journal of biomolecular structure & dynamics 24 3917033
1984 Cloning of the aspartase gene (aspA) of Escherichia coli. Journal of general microbiology 24 6088667
2014 Molecular cloning and functional characterization of porcine DEAD (Asp-Glu-Ala-Asp) box polypeptide 41 (DDX41). Developmental and comparative immunology 23 25086295
2002 A family of activation associated secreted protein (ASP) homologues of Cooperia punctata. Research in veterinary science 22 12443689
2016 A dynamic Asp-Arg interaction is essential for catalysis in microsomal prostaglandin E2 synthase. Proceedings of the National Academy of Sciences of the United States of America 21 26755582
2016 Isomerization of Asp residues plays an important role in αA-crystallin dissociation. The FEBS journal 20 26700637
2012 Isomerization of Asp-Asp motif in model peptides and a monoclonal antibody Fab fragment. Journal of pharmaceutical sciences 20 23280575
2008 Production of C5a by ASP, a serine protease released from Aeromonas sobria. Journal of immunology (Baltimore, Md. : 1950) 20 18714034
2020 Venomics of the asp viper Vipera aspis aspis from France. Journal of proteomics 19 32087377
2017 Site-specific His/Asp phosphoproteomic analysis of prokaryotes reveals putative targets for drug resistance. BMC microbiology 19 28545444
2013 The AgI/II family adhesin AspA is required for respiratory infection by Streptococcus pyogenes. PloS one 19 23638083
2011 Loss of ASP but not ROPN1 reduces mammalian ciliary motility. Cytoskeleton (Hoboken, N.J.) 19 22021175
1981 des-Asp-angiotensin I: its identification in rat blood and confirmation as a substrate for converting enzyme. Endocrinology 19 6256150
2019 Detection of antisense protein (ASP) RNA transcripts in individuals infected with human immunodeficiency virus type 1 (HIV-1). The Journal of general virology 18 30896385
2019 Site-specific analysis of the Asp- and Glu-ADP-ribosylated proteome by quantitative mass spectrometry. Methods in enzymology 18 31606080
1999 Fibrinogen Matsumoto III: a variant with gamma275 Arg-->Cys (CGC-->TGC)--comparison of fibrin polymerization properties with those of Matsumoto I (gamma364 Asp-->His) and Matsumoto II (gamma308 Asn-->Lys). Thrombosis and haemostasis 18 10365751
1999 A critical evaluation of the putative role of C3adesArg (ASP) in lipid metabolism and hyperapobetalipoproteinemia. Molecular immunology 18 10698341
2019 LPS-induced inflammation delays the transportation of ASP+ due to down-regulation of OCTN1/2 in alveolar epithelial cells. Journal of drug targeting 17 31591905
1991 Resonance Raman spectra of bacteriorhodopsin mutants with substitutions at Asp-85, Asp-96, and Arg-82. Photochemistry and photobiology 17 2062880
2022 Anticancer Properties of N,N-dibenzylasparagine as an Asparagine (Asp) analog, Using Colon Cancer Caco-2 Cell Line. Asian Pacific journal of cancer prevention : APJCP 16 35901362
2022 Deciphering the Alphabet of Disorder-Glu and Asp Act Differently on Local but Not Global Properties. Biomolecules 16 36291634
2017 Sequential activities of Dynein, Mud and Asp in centrosome-spindle coupling maintain centrosome number upon mitosis. Journal of cell science 16 28864767
2005 CD117+ small cell lung cancer lacks the asp 816-->val point mutation in exon 17. Histopathology 16 16242000
2024 Balancing the AspC and AspA Pathways of Escherichia coli by Systematic Metabolic Engineering Strategy for High-Efficient l-Homoserine Production. ACS synthetic biology 15 39042380
2022 Anti-Inflammatory and Mineralization Effects of an ASP/PLGA-ASP/ACP/PLLA-PLGA Composite Membrane as a Dental Pulp Capping Agent. Journal of functional biomaterials 15 35997444
2018 Tuning Stacking Interactions between Asp-Arg Salt Bridges and Heterocyclic Drug Fragments. Journal of chemical information and modeling 15 30507185
1999 Arg-gly-Asp (RGD) peptides and peptidomimetics as therapeutics: relevance for renal diseases. Experimental nephrology 15 10213871
1999 Posttranslational deamidation of proteins: the case of hemoglobin J Sardegna [alpha50(CD8)His-->Asn-->Asp]. Clinical chemistry 15 9895333
1985 Studies on toxin of Aspergillus fumigatus. XXII. Fashion of binding of Asp-hemolysin to human erythrocytes and Asp-hemolysin-binding proteins of erythrocyte membranes. Microbiology and immunology 15 3892239
2023 Horizontal gene transfer underlies the painful stings of asp caterpillars (Lepidoptera: Megalopygidae). Proceedings of the National Academy of Sciences of the United States of America 14 37428925
2020 A Pilot Study of the Humoral Response Against the AntiSense Protein (ASP) in HIV-1-Infected Patients. Frontiers in microbiology 14 32117090
2020 Australian snakebite myotoxicity (ASP-23). Clinical toxicology (Philadelphia, Pa.) 14 33156703
2021 The HIV-1 Antisense Gene ASP: The New Kid on the Block. Vaccines 13 34067514
2008 Cord blood ASP is predicted by maternal lipids and correlates with fetal birth weight. Obesity (Silver Spring, Md.) 13 18356838
2005 Arg-Gly-Asp (RGD)-containing peptides increase soluble guanylate cyclase in contractile cells. Cardiovascular research 13 16360131