Affinage

LNPEP

Leucyl-cystinyl aminopeptidase · UniProt Q9UIQ6

Round 2 corrected
Length
1025 aa
Mass
117.3 kDa
Annotated
2026-04-28
130 papers in source corpus 20 papers cited in narrative 20 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LNPEP (IRAP/oxytocinase) is a type II transmembrane zinc metallopeptidase of the M1 aminopeptidase family that cleaves neuropeptide substrates—most notably vasopressin and oxytocin—at the cell surface and functions as the angiotensin IV (AT4) receptor, whose ligands act as competitive inhibitors of its catalytic site (PMID:8550619, PMID:11707427, PMID:12871575, PMID:17684103). LNPEP resides on insulin-responsive GLUT4 storage vesicles and is required for their insulin-stimulated translocation to the plasma membrane, engaging cytoplasmic domain partners including tankyrase (via an RXXPDG motif), p115, and vimentin to coordinate vesicle tethering and exocytosis (PMID:10988299, PMID:12080061, PMID:15800058, PMID:17059388, PMID:21216232). In dendritic cells, LNPEP localizes to Rab14⁺/Syntaxin-6⁺ endosomes where it trims peptides for MHC class I cross-presentation of exogenous antigens (PMID:19498108, PMID:22238454). In T cells, LNPEP maintains endosomal TCR-CD3ζ signaling after clathrin-mediated internalization, and T cell–specific deletion impairs polyclonal anti-tumour immunity (PMID:32487999).

Mechanistic history

Synthesis pass · year-by-year structured walk · 7 steps
  1. 1996 High

    Cloning of LNPEP established it as a type II integral membrane zinc metallopeptidase capable of degrading oxytocin and vasopressin, resolving the molecular identity of placental leucine aminopeptidase.

    Evidence cDNA cloning and peptide sequencing of purified human placental protein

    PMID:8550619

    Open questions at the time
    • No in vivo substrates confirmed
    • Subcellular trafficking unknown
    • Physiological function beyond pregnancy not addressed
  2. 2001 High

    Identification of IRAP as the angiotensin AT4 receptor revealed that AT4 ligands such as angiotensin IV act by competitively inhibiting IRAP catalytic activity rather than signaling through a classical GPCR, reframing the AT4 receptor pharmacology as enzyme inhibition.

    Evidence Protein purification and peptide sequencing from bovine adrenal membranes; radioligand binding and enzyme inhibition assays in IRAP-transfected HEK293T cells

    PMID:11707427 PMID:12871575

    Open questions at the time
    • Whether AT4-mediated cognitive effects are fully explained by IRAP inhibition vs. other mechanisms
    • Structural basis of competitive inhibition not yet resolved
  3. 2001 Medium

    Studies in GLUT4-null mice demonstrated that IRAP and GLUT4 are co-dependent in vesicular trafficking: loss of GLUT4 caused constitutive surface appearance of IRAP, establishing their mutual retention in an insulin-responsive intracellular compartment.

    Evidence Subcellular fractionation and immunofluorescence in GLUT4 knockout mouse adipocytes

    PMID:11394912

    Open questions at the time
    • Whether IRAP itself provides retention signals for the compartment
    • Mechanism of constitutive translocation in GLUT4-null cells
  4. 2002 High

    Mapping the RXXPDG tankyrase-binding motif in IRAP's cytoplasmic domain, and subsequent identification of p115 and vimentin as additional cytoplasmic domain partners, defined a molecular machinery through which IRAP coordinates GLUT4 storage vesicle tethering and insulin-stimulated exocytosis.

    Evidence Yeast two-hybrid, mutagenesis of RXXPDG motif, pull-down/co-IP in 3T3-L1 adipocytes, siRNA knockdown of tankyrase/vimentin with GLUT4 translocation and glucose uptake readouts

    PMID:10988299 PMID:12080061 PMID:15800058 PMID:17059388 PMID:21216232

    Open questions at the time
    • Whether tankyrase poly(ADP-ribosyl)ation of IRAP or a cargo protein is the functional output
    • How p115 and vimentin interactions are coordinated temporally during insulin signaling
  5. 2007 High

    IRAP knockout mice revealed vasopressin as the first confirmed in vivo substrate, with elevated plasma vasopressin and prolonged half-life in null animals, and demonstrated that insulin accelerates vasopressin clearance through IRAP, linking insulin-stimulated IRAP surface translocation to neuropeptide metabolism.

    Evidence IRAP knockout mice, ex vivo adipocyte/muscle cleavage assays, in vivo plasma vasopressin half-life measurements

    PMID:17684103

    Open questions at the time
    • Whether oxytocin is similarly regulated in vivo
    • Contribution of IRAP vs. other peptidases to systemic neuropeptide clearance
  6. 2009 High

    Discovery that IRAP localizes to Rab14⁺ endosomes in dendritic cells and is required for MHC class I cross-presentation opened an entirely new functional axis—endosomal peptide trimming for antigen presentation—distinct from its metabolic and vasoregulatory roles.

    Evidence IRAP-deficient dendritic cells, co-IP with MHC class I, in vitro and in vivo cross-presentation assays; DC subset comparisons showing IRAP-dependent and -independent cross-presentation pathways

    PMID:19498108 PMID:19918052 PMID:22238454

    Open questions at the time
    • Full repertoire of peptides trimmed by IRAP in endosomes
    • Whether IRAP enzymatic activity vs. scaffolding function is required for cross-presentation
    • Relationship between IRAP and ERAP1/2 in antigen processing
  7. 2020 High

    Conditional T cell–specific IRAP deletion revealed that IRAP maintains an endosomal compartment (marked by Syntaxin 6) essential for sustained TCR-CD3ζ signaling after receptor internalization, with loss of IRAP enhancing surface TCR levels but paradoxically impairing signaling output and anti-tumour immunity.

    Evidence T cell–conditional IRAP knockout, TCR internalization and CD3ζ phosphorylation assays, colocalization with Syntaxin 6 endosomes, in vivo tumour challenge

    PMID:32487999

    Open questions at the time
    • Whether IRAP enzymatic activity or its role as a compartment organizer drives TCR signaling maintenance
    • Applicability to other immune synapse contexts beyond tumour immunity
    • Potential redundancy with ERAP1/2 in T cell endosomes

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include whether IRAP's catalytic activity versus its structural/trafficking role is the primary driver in cross-presentation and TCR signaling, the structural basis of AT4 ligand competitive inhibition, and how IRAP's three major functional axes—metabolic vesicle trafficking, antigen presentation, and endosomal TCR signaling—are coordinated or independently regulated across cell types.
  • No crystal structure of full-length IRAP with bound AT4 ligand
  • Enzymatic vs. scaffolding contribution not separated by catalytic-dead mutants in immune contexts
  • Physiological relevance of S-acylation to IRAP trafficking in insulin-responsive tissues unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0016787 hydrolase activity 3 GO:0001618 virus receptor activity 2
Localization
GO:0031410 cytoplasmic vesicle 7 GO:0005886 plasma membrane 4 GO:0005768 endosome 3
Pathway
R-HSA-168256 Immune System 4 R-HSA-392499 Metabolism of proteins 4 R-HSA-5653656 Vesicle-mediated transport 4 R-HSA-162582 Signal Transduction 3
Partners
GM130RAB14SLC2A4STX6TNKSVIM
Complex memberships
GLUT4 storage vesicle complex

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 Human placental leucine aminopeptidase (P-LAP/LNPEP) was cloned and characterized as a type II integral membrane zinc metallopeptidase containing the HEXXH consensus zinc-binding motif, capable of degrading peptide hormones such as oxytocin and vasopressin, and shown to be synthesized as an integral membrane protein that can be released into blood under physiological conditions. cDNA cloning, peptide sequencing of purified protein, Northern blot analysis The Journal of biological chemistry High 8550619
2000 Tankyrase, a poly(ADP-ribose) polymerase, was identified as a binding partner of IRAP (insulin-responsive aminopeptidase/LNPEP). The interaction involves the ankyrin repeats of tankyrase and a defined sequence (96RQSPDG101) in the IRAP cytoplasmic domain. Tankyrase co-localizes with GLUT4 storage vesicles and IRAP in the juxtanuclear region of adipocytes, and is a substrate for MAPK phosphorylation upon insulin stimulation. Subcellular fractionation, immunofluorescence colocalization, specific binding assay, yeast two-hybrid, domain mapping The Journal of biological chemistry High 10988299
2001 The angiotensin AT4 receptor was identified as IRAP (insulin-regulated aminopeptidase/LNPEP) by protein purification and peptide sequencing. HEK293T cells transfected with IRAP exhibit typical AT4 receptor binding characteristics, and AT4 receptor ligands (angiotensin IV, LVV-hemorphin 7) dose-dependently inhibit IRAP catalytic activity, suggesting they act by inhibiting IRAP-mediated cleavage of neuropeptide substrates. Protein purification, peptide sequencing, radioligand binding in transfected cells, enzyme activity inhibition assays, immunohistochemistry and in situ hybridization for brain distribution The Journal of biological chemistry High 11707427
2001 In GLUT4-null mice, IRAP exhibited abnormal subcellular distribution and impaired insulin-stimulated translocation; in adipocytes lacking GLUT4, the compartment containing IRAP traffics constitutively to the cell surface, demonstrating that IRAP and GLUT4 are co-dependent in their vesicular trafficking and that GLUT4 is required for proper intracellular retention of IRAP. Western blot analysis of GLUT4 null mouse tissues (adipocytes, skeletal muscle, heart), subcellular fractionation, immunofluorescence Biochemical and biophysical research communications Medium 11394912
2002 A novel RXXPDG motif shared by IRAP, TAB182, and human TRF1 mediates their binding to tankyrase ankyrin repeat domains. Mutation of this motif abrogates tankyrase binding, establishing this hexapeptide as the core tankyrase-recognition sequence in IRAP's cytoplasmic domain. Yeast two-hybrid, in vitro binding assays with domain truncations and motif mutations The Journal of biological chemistry High 12080061
2003 AT4 receptor ligands including angiotensin IV, Nle1-Ang IV, divalinal-Ang IV, and LVV-hemorphin-7 are potent competitive inhibitors of IRAP catalytic activity, binding to the catalytic site; vasopressin, oxytocin, and met-enkephalin were identified as rapid substrates for IRAP cleavage. Recombinant human IRAP enzyme activity assay, competitive kinetics analysis, radioligand displacement from IRAP-HEK293T membranes Journal of neurochemistry High 12871575
2005 p115, a peripheral membrane protein involved in membrane trafficking, was identified as a binding partner of the IRAP cytoplasmic domain (residues 1-109). p115 partially co-localizes with GLUT4 and IRAP in the perinuclear region of adipocytes. Overexpression of the N-terminal p115 construct completely inhibited insulin-stimulated GLUT4 translocation, while having no effect on GLUT1 distribution, establishing a specific role for p115 in GLUT4/IRAP vesicle tethering. Affinity pull-down with IRAP cytoplasmic domain, immunofluorescence colocalization, overexpression dominant-negative in murine adipocytes Molecular biology of the cell Medium 15800058
2005 LNPEP/IRAP and related enzymes P-LAP and L-RAP constitute the 'Oxytocinase subfamily' of M1 aminopeptidases, sharing HEXXH(X)18E zinc-binding and GAMEN motifs essential for enzymatic activity. P-LAP/LNPEP translocates from intracellular vesicles to plasma membrane in a stimulus-dependent manner, unlike ER-retained subfamily members, and plays roles in pregnancy homeostasis, memory retention, blood pressure regulation, and antigen presentation. Biochemical characterization, sequence analysis, subcellular localization studies Biochimica et biophysica acta Medium 16054015
2007 Vasopressin was identified as the first confirmed physiological substrate for IRAP in vivo. IRAP-deficient mice failed to process vasopressin from its N-terminus in adipocytes and skeletal muscle, vasopressin exhibited a threefold increased plasma half-life in IRAP-/- mice, and endogenous plasma vasopressin was elevated twofold. Insulin increased vasopressin clearance from control but not IRAP-/- mice, revealing a novel IRAP-dependent insulin effect on vasopressin metabolism. IRAP knockout mouse model, ex vivo cleavage assays in isolated adipocytes and skeletal muscle, in vivo vasopressin injection and plasma half-life measurement, ELISA for plasma and brain vasopressin levels American journal of physiology. Endocrinology and metabolism High 17684103
2007 IRAP is required for insulin-stimulated GLUT4 storage vesicle (GSV) translocation: IRAP knockdown impaired insulin-stimulated GLUT4 translocation without affecting GLUT4 expression, while GLUT4 knockdown did not impair IRAP translocation. Tankyrase knockdown attenuated insulin-stimulated GSV translocation and glucose uptake without disrupting insulin-induced phosphorylation cascades, and tankyrase knockdown altered basal-state endosomal partitioning of GLUT4 and IRAP; these effects were reproduced by a general PARP inhibitor. siRNA knockdown in 3T3-L1 adipocytes, insulin-stimulated translocation assays, glucose uptake assays, iodixanol density gradient fractionation, PARP inhibitor (PJ34) treatment The Biochemical journal High 17059388
2009 IRAP was localized to a Rab14+ endosomal storage compartment in human dendritic cells where it interacted with MHC class I molecules. IRAP deficiency compromised cross-presentation of exogenous antigens in vitro and in vivo by impairing N-terminal peptide trimming in this endosomal compartment, without affecting endogenous presentation, establishing IRAP as a component of the MHC class I cross-presentation pathway. Immunofluorescence localization, co-immunoprecipitation of IRAP with MHC class I, IRAP-deficient dendritic cell cross-presentation assays in vitro and in vivo Science High 19498108
2009 Cross-presentation in inflammatory monocyte-derived dendritic cells (moDC) requires IRAP, while steady-state CD8+ DCs use an IRAP-independent pathway for cross-priming. IRAP and mannose receptor are dispensable for cross-presentation by CD8+ DCs, and no diversion of endocytosed antigen into IRAP-containing endosomes was detected in these cells, demonstrating mechanistic differences between DC subsets. IRAP-deficient and mannose receptor-deficient DC cross-presentation assays, antigen trafficking experiments, in vivo cross-priming assays Proceedings of the National Academy of Sciences of the United States of America High 19918052
2009 IRAP knockout mice showed normal reproductive profiles (gestational period, litter size, parturition), and IRAP was undetectable in pregnant mouse serum. The cleavage site (Phe154-Ala155) required to release soluble IRAP is restricted to members of the hominidae family, explaining the absence of circulating IRAP in mice during pregnancy and indicating species-specific regulation of IRAP shedding. IRAP knockout mouse phenotypic analysis, Western blot of pregnant mouse serum, fluorimetric IRAP enzyme assay, sequence comparison across species Peptides Medium 19647771
2011 Vimentin was identified as a cytoplasmic domain-binding partner of IRAP using pull-down assays and co-immunoprecipitation in 3T3-L1 adipocytes. Depletion of vimentin decreased insulin-stimulated GLUT4 translocation to the plasma membrane, suggesting vimentin tethers GLUT4 storage vesicles to the cytoskeleton through its interaction with IRAP. IRAP cytoplasmic domain pull-down, co-immunoprecipitation in 3T3-L1 adipocytes, vimentin siRNA knockdown with GLUT4 translocation assay Biochemical and biophysical research communications Medium 21216232
2012 In steady-state conventional dendritic cells (cDCs), IRAP co-localizes with Rab14 and Syntaxin 6 in regulated endosomal storage compartments, and IRAP deficiency compromises cross-presentation of both soluble and particulate antigens. IRAP recruitment to phagosomes was stronger in CD8+ DCs, contributing to their superior cross-presentation efficacy. Immunofluorescence colocalization, IRAP-deficient DC cross-presentation assays for soluble and particulate antigens Journal of immunology Medium 22238454
2013 A missense variant rs2303138 (p.Ala763Thr) in LNPEP was associated with psoriasis susceptibility. LNPEP was significantly downregulated in psoriatic lesions, and pathway analysis indicated LNPEP involvement in the renin-angiotensin system, suggesting its role in connecting cardiovascular/metabolic pathways to inflammatory skin disease. GWAS with replication cohorts (total >18,000 subjects), expression analysis of LNPEP in psoriatic vs. control skin The Journal of investigative dermatology Low 23897274
2015 Approximately 60% of IRAP is S-acylated in 3T3-L1 adipocytes. Site-directed mutagenesis mapped S-acylation to two cytoplasmic cysteine residues, one within the cytoplasmic side of the transmembrane domain and one just upstream; results suggest these cysteines are modified in a mutually exclusive manner. However, mutation of these cysteines did not affect plasma membrane localization in HEK293T cells, indicating S-acylation is not essential for trafficking through the secretory pathway. Semi-quantitative acyl-RAC technique, site-directed mutagenesis of cysteine residues, plasma membrane localization assay in HEK293T cells Scientific reports Medium 26198666
2017 27-Hydroxycholesterol (27-OH) increased the levels and activity of IRAP in the brain, countered IRAP antagonist angiotensin IV (AngIV)-mediated glucose uptake, and enhanced levels of aminopeptidase N (AP-N). These effects were mediated by liver X receptors, revealing a molecular link between cholesterol metabolism, IRAP activity, and neuronal glucose uptake via the GLUT4/IRAP system. In vivo brain glucose PET imaging, GLUT4/IRAP expression analysis, AngIV treatment in IRAP-modulated cells, liver X receptor pathway analysis The Journal of experimental medicine Medium 28213512
2020 LNPEP/IRAP is proposed as the evolutionary progenitor of the ERAP1/ERAP2/LNPEP gene cluster on chromosome 5, from which ERAP1 and ERAP2 may have derived by gene duplication. LNPEP's functions include regulation of the renin-angiotensin system (at cell membrane as AT4/angiotensin IV receptor) and contribution to antigen cross-presentation in endosomal vesicles; its role in antigen presentation is thought to be evolutionarily acquired later than its vasoregulatory function. Comparative genomic/evolutionary sequence analysis, review of functional biochemical data Frontiers in immunology Low 32793222
2020 Upon TCR ligation, the TCR-CD3ζ complex undergoes clathrin-mediated internalization while maintaining CD3ζ signalling from endosomal vesicles containing IRAP and the SNARE protein Syntaxin 6. IRAP deletion destabilized this compartment, enhanced plasma membrane TCR-CD3ζ expression but compromised overall CD3ζ signalling. Mice with T cell-specific IRAP deletion failed to develop efficient polyclonal anti-tumour responses, establishing IRAP-dependent endosomal TCR signalling as essential for T cell activation. IRAP conditional knockout in T cells, TCR internalization assays, CD3ζ signalling analysis (phosphorylation), immunofluorescence colocalization of TCR-CD3ζ with IRAP/Syntaxin 6 endosomes, in vivo anti-tumour response assays Nature communications High 32487999

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 3725 23128233
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
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
1999 Transcription activation by catabolite activator protein (CAP). Journal of molecular biology 654 10550204
2015 A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface. Cell 433 26638075
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2001 Evidence that the angiotensin IV (AT(4)) receptor is the enzyme insulin-regulated aminopeptidase. The Journal of biological chemistry 379 11707427
1990 Monomethylated cap structures facilitate RNA export from the nucleus. Cell 355 2208274
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2001 Ceramide enables fas to cap and kill. The Journal of biological chemistry 313 11287428
2012 A high-throughput approach for measuring temporal changes in the interactome. Nature methods 273 22863883
2007 A hypoxia-controlled cap-dependent to cap-independent translation switch in breast cancer. Molecular cell 253 17996713
2004 Functional proteomics mapping of a human signaling pathway. Genome research 247 15231748
2000 Tankyrase is a golgi-associated mitogen-activated protein kinase substrate that interacts with IRAP in GLUT4 vesicles. The Journal of biological chemistry 241 10988299
2009 IRAP identifies an endosomal compartment required for MHC class I cross-presentation. Science (New York, N.Y.) 216 19498108
1998 Interferon-gamma can stimulate post-proteasomal trimming of the N terminus of an antigenic peptide by inducing leucine aminopeptidase. The Journal of biological chemistry 211 9668046
2004 Cap-dependent and cap-independent translation in eukaryotic systems. Gene 205 15145049
2011 Structural basis and sequence rules for substrate recognition by Tankyrase explain the basis for cherubism disease. Cell 202 22153077
2018 An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations. Nature communications 201 29568061
2015 Discovery of m(7)G-cap in eukaryotic mRNAs. Proceedings of the Japan Academy. Series B, Physical and biological sciences 192 26460318
2001 Suppression of cap-dependent translation in mitosis. Genes & development 187 11511540
2000 Two new proteases in the MHC class I processing pathway. Nature immunology 185 11062501
2018 LZTR1 is a regulator of RAS ubiquitination and signaling. Science (New York, N.Y.) 180 30442766
1996 Human placental leucine aminopeptidase/oxytocinase. A new member of type II membrane-spanning zinc metallopeptidase family. The Journal of biological chemistry 178 8550619
2018 mRNA cap regulation in mammalian cell function and fate. Biochimica et biophysica acta. Gene regulatory mechanisms 175 30312682
2009 Regulation of mRNA cap methylation. The Biochemical journal 168 20025612
2014 Cap-binding complex (CBC). The Biochemical journal 166 24354960
2007 Integral and associated lysosomal membrane proteins. Traffic (Copenhagen, Denmark) 163 17897319
1996 General RNA binding proteins render translation cap dependent. The EMBO journal 156 9003790
2003 Angiotensin AT4 ligands are potent, competitive inhibitors of insulin regulated aminopeptidase (IRAP). Journal of neurochemistry 149 12871575
2006 Modulating RssB activity: IraP, a novel regulator of sigma(S) stability in Escherichia coli. Genes & development 141 16600914
2005 The oxytocinase subfamily of M1 aminopeptidases. Biochimica et biophysica acta 140 16054015
2019 Mapping the proximity interaction network of the Rho-family GTPases reveals signalling pathways and regulatory mechanisms. Nature cell biology 137 31871319
2009 Different cross-presentation pathways in steady-state and inflammatory dendritic cells. Proceedings of the National Academy of Sciences of the United States of America 135 19918052
2002 Identification of a tankyrase-binding motif shared by IRAP, TAB182, and human TRF1 but not mouse TRF1. NuMA contains this RXXPDG motif and is a novel tankyrase partner. The Journal of biological chemistry 131 12080061
2010 Enzymology of RNA cap synthesis. Wiley interdisciplinary reviews. RNA 129 21956912
2019 The Functional Proximal Proteome of Oncogenic Ras Includes mTORC2. Molecular cell 124 30639242
2019 Anakinra for corticosteroid-dependent and colchicine-resistant pericarditis: The IRAP (International Registry of Anakinra for Pericarditis) study. European journal of preventive cardiology 123 31610707
2007 ppGpp regulation of RpoS degradation via anti-adaptor protein IraP. Proceedings of the National Academy of Sciences of the United States of America 112 17640895
2007 Insulin-stimulated exocytosis of GLUT4 is enhanced by IRAP and its partner tankyrase. The Biochemical journal 108 17059388
2020 Molecular Mechanisms of the Efficacy of Cold Atmospheric Pressure Plasma (CAP) in Cancer Treatment. Cancers 101 31979114
2006 IRAP and REMAP for retrotransposon-based genotyping and fingerprinting. Nature protocols 96 17406494
2008 Capturing protein tails by CAP-Gly domains. Trends in biochemical sciences 95 18835717
2020 The Cap-Snatching Mechanism of Bunyaviruses. Trends in microbiology 89 31948728
2004 'Cap-tabolism'. Trends in biochemical sciences 87 15362228
2011 RAM/Fam103a1 is required for mRNA cap methylation. Molecular cell 86 22099306
2007 Vasopressin is a physiological substrate for the insulin-regulated aminopeptidase IRAP. American journal of physiology. Endocrinology and metabolism 84 17684103
1993 CAP interacts with RNA polymerase in solution in the absence of promoter DNA. Nature 83 8393148
2002 Titin-cap associates with, and regulates secretion of, Myostatin. Journal of cellular physiology 81 12209887
2008 Analysis of flavivirus NS5 methyltransferase cap binding. Journal of molecular biology 78 19101564
2005 p115 Interacts with the GLUT4 vesicle protein, IRAP, and plays a critical role in insulin-stimulated GLUT4 translocation. Molecular biology of the cell 78 15800058
2000 Inhibin-alpha CD99, HEA125, PLAP, and chromogranin immunoreactivity in testicular neoplasms and the androgen insensitivity syndrome. Human pathology 78 11014571
1991 Heat shock impairs the interaction of cap-binding protein complex with 5' mRNA cap. The Journal of biological chemistry 77 1993658
2018 Insight into Influenza: A Virus Cap-Snatching. Viruses 69 30453478
2017 27-Hydroxycholesterol impairs neuronal glucose uptake through an IRAP/GLUT4 system dysregulation. The Journal of experimental medicine 66 28213512
2014 RNA methyltransferases involved in 5' cap biosynthesis. RNA biology 64 25626080
2021 Upregulation of RNA cap methyltransferase RNMT drives ribosome biogenesis during T cell activation. Nucleic acids research 61 34125914
2004 Role of the insulin-regulated aminopeptidase IRAP in insulin action and diabetes. Biological & pharmaceutical bulletin 60 15187412
2011 Autologous conditioned serum: the comparative cytokine profiles of two commercial methods (IRAP and IRAP II) using equine blood. Equine veterinary journal 59 21496084
2021 A safety cap protects hydrogenase from oxygen attack. Nature communications 58 33531463
2009 HIV- 1 protease inhibits Cap- and poly(A)-dependent translation upon eIF4GI and PABP cleavage. PloS one 56 19956697
2020 The multifaceted eukaryotic cap structure. Wiley interdisciplinary reviews. RNA 54 33300197
2019 Differential requirements for cyclase-associated protein (CAP) in actin-dependent processes of Toxoplasma gondii. eLife 49 31577230
2012 Conventional dendritic cells require IRAP-Rab14 endosomes for efficient cross-presentation. Journal of immunology (Baltimore, Md. : 1950) 49 22238454
2008 PLAP-1/asporin inhibits activation of BMP receptor via its leucine-rich repeat motif. Biochemical and biophysical research communications 49 18407830
2012 miR-21 and miR-101 regulate PLAP-1 expression in periodontal ligament cells. Molecular medicine reports 48 22367347
1996 Mammalian CAP interacts with CAP, CAP2, and actin. Journal of cellular biochemistry 46 8761950
2013 Identification of a missense variant in LNPEP that confers psoriasis risk. The Journal of investigative dermatology 45 23897274
2010 The root cap at the forefront. Comptes rendus biologies 43 20371108
2006 Adenosine kinase modulates root gravitropism and cap morphogenesis in Arabidopsis. Plant physiology 43 16891550
2023 Mechanisms of fibrous cap formation in atherosclerosis. Frontiers in cardiovascular medicine 40 37671141
2023 Cholesterol-Amino-Phosphate (CAP) Derived Lipid Nanoparticles for Delivery of Self-Amplifying RNA and Restoration of Spermatogenesis in Infertile Mice. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 39 36748274
2016 Cap-like structures in bacterial RNA and epitranscriptomic modification. Current opinion in microbiology 38 26779928
2011 An unconventional pathway of mRNA cap formation by vesiculoviruses. Virus research 38 21945214
2020 IRAP-dependent endosomal T cell receptor signalling is essential for T cell responses. Nature communications 37 32487999
2016 The i6A37 tRNA modification is essential for proper decoding of UUX-Leucine codons during rpoS and iraP translation. RNA (New York, N.Y.) 37 26979278
2013 Phosphoregulation of the titin-cap protein telethonin in cardiac myocytes. The Journal of biological chemistry 37 24280220
1993 Responses of purified phospholipases A2 to phospholipase A2 activating protein (PLAP) and melittin. Biochimica et biophysica acta 37 8431486
2017 Boundary cap cells in development and disease. Current opinion in neurobiology 35 29174469
2006 Regulation of PLAP-1 expression in periodontal ligament cells. Journal of dental research 35 16632759
2006 Cyclic insulin-regulated aminopeptidase (IRAP)/AT4 receptor ligands. Journal of peptide science : an official publication of the European Peptide Society 35 16967438
2022 HIV-1 hypermethylated guanosine cap licenses specialized translation unaffected by mTOR. Proceedings of the National Academy of Sciences of the United States of America 34 34949712
2020 The Multifaceted Nature of Aminopeptidases ERAP1, ERAP2, and LNPEP: From Evolution to Disease. Frontiers in immunology 34 32793222
2001 GLUT4 ablation in mice results in redistribution of IRAP to the plasma membrane. Biochemical and biophysical research communications 33 11394912
2008 Opposing effects of inhibiting cap addition and cap methylation on polyadenylation during vesicular stomatitis virus mRNA synthesis. Journal of virology 32 19073725
2020 CAPt'n of Actin Dynamics: Recent Advances in the Molecular, Developmental and Physiological Functions of Cyclase-Associated Protein (CAP). Frontiers in cell and developmental biology 31 33072768
2020 Combinatorial Effect of Cold Atmosphere Plasma (CAP) and the Anticancer Drug Cisplatin on Oral Squamous Cell Cancer Therapy. International journal of molecular sciences 31 33076565
2015 PLAP-1/Asporin Regulates TLR2- and TLR4-induced Inflammatory Responses. Journal of dental research 30 26399972
2021 Pattern of placental alkaline phosphatase (PLAP) expression in human tumors: a tissue microarray study on 12,381 tumors. The journal of pathology. Clinical research 28 34363325
2020 Protein glycation and oxidation inhibitory activity of Centella asiatica phenolics (CAP) in glucose-mediated bovine serum albumin glycoxidation. Food chemistry 28 32615389
2016 mRNA Cap Methylation in Pluripotency and Differentiation. Cell reports 28 27452456
2017 Structural insights into reptarenavirus cap-snatching machinery. PLoS pathogens 27 28505175
2010 Myc Regulation of mRNA Cap Methylation. Genes & cancer 27 21170289
2008 Ligands to the (IRAP)/AT4 receptor encompassing a 4-hydroxydiphenylmethane scaffold replacing Tyr2. Bioorganic & medicinal chemistry 27 18556208
2022 Engineering CpG-ASO-Pt-Loaded Macrophages (CAP@M) for Synergistic Chemo-/Gene-/Immuno-Therapy. Advanced healthcare materials 26 35668035
2013 Putrescine importer PlaP contributes to swarming motility and urothelial cell invasion in Proteus mirabilis. The Journal of biological chemistry 26 23572531
1989 Serum placental-like alkaline phosphatase (PLAP): a novel combined enzyme linked immunoassay for monitoring ovarian cancer. Journal of clinical pathology 26 2921344
2014 Inhibitory effects of PLAP-1/asporin on periodontal ligament cells. Journal of dental research 25 24453179
2024 Cold atmospheric plasma (CAP): a revolutionary approach in dermatology and skincare. European journal of medical research 24 39367460
2014 PRMT5 is essential for the eIF4E-mediated 5'-cap dependent translation. Biochemical and biophysical research communications 24 25234597
1998 Abnormal mucus in cap polyposis. Gut 24 9518233
2024 The mechanism of mRNA cap recognition. Nature 23 39663447
2015 S-acylation of the Insulin-Responsive Aminopeptidase (IRAP): Quantitative analysis and Identification of Modified Cysteines. Scientific reports 23 26198666
2008 Cap-dependent translation initiation and memory. Progress in brain research 23 18394468
2023 Arabidopsis DXO1 activates RNMT1 to methylate the mRNA guanosine cap. Nature communications 22 36639378
2022 Plap-1 lineage tracing and single-cell transcriptomics reveal cellular dynamics in the periodontal ligament. Development (Cambridge, England) 22 36245218
2021 Loss of androgen receptor promotes HCC invasion and metastasis via activating circ-LNPEP/miR-532-3p/RAB9A signal under hypoxia. Biochemical and biophysical research communications 22 33862456
2015 Diversity and relationships of Crocus sativus and its relatives analysed by inter-retroelement amplified polymorphism (IRAP). Annals of botany 22 26138822
2014 Distinct features of cap binding by eIF4E1b proteins. Journal of molecular biology 22 25463438
2011 Vimentin binds IRAP and is involved in GLUT4 vesicle trafficking. Biochemical and biophysical research communications 22 21216232
2019 CAPAM: The mRNA Cap Adenosine N6-Methyltransferase. Trends in biochemical sciences 21 30679132
2014 Transposon-based tagging: IRAP, REMAP, and iPBS. Methods in molecular biology (Clifton, N.J.) 21 24415478
1999 Stimulation of Golgi membrane tubulation and retrograde trafficking to the ER by phospholipase A(2) activating protein (PLAP) peptide. Journal of cellular biochemistry 21 10440936
2014 Development of IRAP- and REMAP-derived SCAR markers for marker-assisted selection of the stripe rust resistance gene Yr15 derived from wild emmer wheat. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 20 25388968
2000 Increase in cap- and IRES-dependent protein synthesis by overproduction of translation initiation factor eIF4G. Biochemical and biophysical research communications 20 11027650
2019 Molar Bud-to-Cap Transition Is Proliferation Independent. Journal of dental research 19 31393749
2014 Genetic variability and structure of Quercus brantii assessed by ISSR, IRAP and SCoT markers. Gene 19 25241382
2020 Cap-independent translation initiation of the unspliced RNA of retroviruses. Biochimica et biophysica acta. Gene regulatory mechanisms 18 32450258
2009 Bunyavirus N: eIF4F surrogate and cap-guardian. Cell cycle (Georgetown, Tex.) 18 19342890
2009 Reproduction and maternal behavior in insulin-regulated aminopeptidase (IRAP) knockout mice. Peptides 18 19647771
2000 Actin cytoskeleton: putting a CAP on actin polymerization. Current biology : CB 18 11050402
1983 CAP binding to B and Z forms of DNA. Nucleic acids research 18 6344018