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Showing LRPAP1 — RAP is a alias.

LRPAP1

Alpha-2-macroglobulin receptor-associated protein · UniProt P30533

Length
357 aa
Mass
41.5 kDa
Annotated
2026-06-10
100 papers in source corpus 15 papers cited in narrative 15 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LRPAP1 (RAP) is a Ca2+-dependent molecular chaperone of the LDL receptor family that escorts receptor folding and traffic through the secretory pathway while acting as a universal inhibitor of premature ligand binding (PMID:7579068, PMID:11580203). It binds megalin (LRP2/gp330) and LRP1 at two distinct sites (residues 85-148 and 178-248) with a separate heparin-binding region (residues 261-323), interactions that are strictly Ca2+-dependent (PMID:7512726). Structurally it is built from three independent three-helix bundles joined by flexible linkers, an architecture that permits multiple conformations during receptor engagement (PMID:17656581), and it resides predominantly in the rough endoplasmic reticulum of epithelial cells (PMID:8223699). Its activity is further tuned by calmodulin binding and phosphorylation: CaM-kinase II and casein kinase II phosphorylate serines in its D2 and D3 domains, and calcineurin reverses this modification (PMID:8861945). Beyond its intracellular escort role, LRPAP1 modulates receptor-mediated handling of multiple ligands—mediating saturable, megalin-dependent transcytosis across the blood-brain barrier (PMID:15383619) and engaging LRP to drive APP-independent, ERK2-linked signaling in neurons (PMID:23061396). A secreted form binds the IFNAR1 extracellular domain through its N-terminus to trigger IFNAR1 ubiquitination and degradation, a mechanism viral proteases exploit to suppress interferon signaling (PMID:37743411). Loss-of-function frameshift mutations in LRPAP1 cause autosomal recessive early-onset high myopia in humans (PMID:25525168), and zebrafish lrpap1 knockout reproduces myopia through TGF-β-induced scleral apoptosis (PMID:36261846).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1994 High

    Defining where and how RAP physically engages LDL receptor family members was needed to explain its inhibitory and escort activities; mapping resolved two distinct Ca2+-dependent receptor-binding sites plus a separate heparin site.

    Evidence Domain-mapped in vitro binding (ligand blotting, affinity chromatography, sedimentation) with overlapping RAP fusion fragments and radiolabeled heparin assays

    PMID:7512726

    Open questions at the time
    • Does not define stoichiometry or order of the two-site engagement in vivo
    • Functional consequence of the heparin-binding site not resolved
  2. 1993 High

    The subcellular site of RAP action was uncertain; controlled fixation experiments established RER residency and showed that apparent brush-border localization was a processing artifact, anchoring its chaperone role to the ER.

    Evidence Immunocytochemistry on PLP-fixed vs. snap-frozen rat kidney with controlled redistribution experiments and fusion-protein binding

    PMID:8223699

    Open questions at the time
    • Does not address how RAP dissociates from receptors after ER transit
    • Secreted/extracellular pool not characterized here
  3. 1995 Medium

    Synthesis of field data assigned RAP a dual function as an ER folding chaperone for megalin and a surface ligand-binding inhibitor, framing its role in receptor biogenesis.

    Evidence Review integrating co-purification, ligand-inhibition, and ER localization data

    PMID:7579068

    Open questions at the time
    • Review-level synthesis rather than new primary data
    • Mechanism separating folding from inhibition not resolved
  4. 1996 High

    Whether RAP itself is regulated was unknown; reconstituted assays showed it binds calmodulin Ca2+/pH-dependently and is phosphorylated on D2/D3 serines by CaM-kinase II and casein kinase II, reversed by calcineurin.

    Evidence In vitro kinase/phosphatase and calmodulin-binding assays with domain fragments, confirmed by 32P labeling in cells

    PMID:8861945

    Open questions at the time
    • Functional effect of phosphorylation on receptor binding not established
    • Cellular trigger for phosphorylation unknown
  5. 1996 Medium

    RAP's role in lipoprotein metabolism was addressed by quantifying its contribution to LPL clearance, distinguishing an LRP-mediated RAP-sensitive route from a dominant proteoglycan route.

    Evidence 125I-LPL degradation assays in adipocytes with RAP inhibition, heparinase/PI-PLC treatment, and 35SO4 proteoglycan labeling

    PMID:8978495

    Open questions at the time
    • Identifies pathway contribution rather than direct molecular mechanism
    • Single lab, single cell type
  6. 2001 Medium

    RAP-sensitive ligand handling was extended to transthyretin, implicating an unidentified LDL-receptor-family member in hepatic TTR internalization.

    Evidence Uptake competition with RAP and cross-linking of 125I-TTR in hepatoma lines and primary hepatocytes

    PMID:11278770

    Open questions at the time
    • Receptor identity not established
    • Single lab
  7. 2001 Medium

    A second review consolidated the escort-protein model, asserting RAP prevents premature ligand interactions and promotes folding independently of ligand inhibition.

    Evidence Review of co-purification, transport, and ER localization data

    PMID:11580203

    Open questions at the time
    • Review synthesis, no new primary data
    • Separation of folding vs. inhibition functions not directly tested here
  8. 2004 High

    Whether RAP could move across barriers was tested; pharmacokinetic and cell-based assays established saturable, megalin-mediated transcytosis delivering RAP to brain parenchyma.

    Evidence 125I-RAP pharmacokinetics, in situ brain perfusion, capillary depletion, and megalin-transfected MDCK transport assays

    PMID:15383619

    Open questions at the time
    • Physiological cargo/relevance of RAP transcytosis unclear
    • Does not address fate of RAP in parenchyma
  9. 2007 High

    The structural basis for RAP's conformational versatility was resolved as three independent three-helix bundles connected by flexible linkers.

    Evidence NMR structure of domain 2 plus SANS with simulated annealing for overall architecture

    PMID:17656581

    Open questions at the time
    • No co-structure with a receptor
    • Conformational states during binding not directly visualized
  10. 2012 Medium

    RAP-LRP engagement was shown to have signaling output, stimulating axon growth via ERK2 independently of APP while potentiating APP's inhibitory effect.

    Evidence Neurite outgrowth in WT vs. APP-knockout neurons with RAP/sAPPa treatment and ERK2 readout

    PMID:23061396

    Open questions at the time
    • Receptor mediating the ERK2 response not pinpointed
    • Single lab, single study
  11. 2014 Medium

    A causal human disease link was established by finding a homozygous LRPAP1 frameshift co-segregating with autosomal recessive early-onset high myopia.

    Evidence Whole-exome sequencing of high-myopia patients, Sanger confirmation, family co-segregation, control absence

    PMID:25525168

    Open questions at the time
    • No functional assay in this study
    • Mechanism linking LRPAP1 loss to myopia not addressed here
  12. 2018 Medium

    An unexpected role as a B-cell receptor autoantigen was demonstrated, with LRPAP1 driving chronic BCR signaling in a subset of mantle cell lymphomas.

    Evidence Recombinant BCR expression from MCL patients/cell lines, antigen screening, BCR activation, and LRPAP1-ETA' immunotoxin killing

    PMID:29955130

    Open questions at the time
    • Mechanism of LRPAP1 autoantigen exposure unknown
    • Single lab
  13. 2022 High

    The mechanism behind LRPAP1-linked myopia was defined in zebrafish: lrpap1 loss activates TGF-β signaling and scleral apoptosis, with bidirectional pharmacological rescue confirming the pathway.

    Evidence CRISPR lrpap1 knockout zebrafish with refraction, scleral EM, RNA-seq, TUNEL, and TGF-β agonist/inhibitor rescue

    PMID:36261846

    Open questions at the time
    • Direct molecular link between RAP loss and TGF-β activation not defined
    • Mammalian confirmation absent
  14. 2023 High

    A secreted extracellular function was uncovered: LRPAP1 binds IFNAR1 via its N-terminus to drive its ubiquitination and degradation, a route co-opted by viral proteases for immune evasion.

    Evidence Binding, ubiquitination, and degradation assays in vitro/ex vivo/in vivo, N-terminal peptide mapping, a2M inhibition, and multi-virus infection assays

    PMID:37743411

    Open questions at the time
    • Ubiquitin ligase mediating IFNAR1 degradation not identified
    • How secreted LRPAP1 traffics to IFNAR1 unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How LRPAP1's intracellular chaperone role and its secreted extracellular signaling/degradation roles are coordinated, and which receptors mediate its diverse phenotypes, remain unresolved.
  • No co-structure of RAP with any receptor
  • E3 ligase for IFNAR1 unknown
  • Direct mechanistic bridge from RAP loss to scleral TGF-β activation undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0044183 protein folding chaperone 2 GO:0140313 molecular sequestering activity 2
Localization
GO:0005783 endoplasmic reticulum 3 GO:0005576 extracellular region 1
Pathway
R-HSA-392499 Metabolism of proteins 2 R-HSA-168256 Immune System 1 R-HSA-9609507 Protein localization 1
Partners
CALM1CAMK2IFNAR1LRP1LRP2TTR

Evidence

Reading pass · 15 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 RAP (LRPAP1) binds to gp330 (megalin/LRP2) and LRP at two distinct sites (amino acids 85-148 and 178-248 of RAP), with binding being Ca2+-dependent. A separate heparin-binding site was mapped to amino acids 261-323. These domains are distinct from the Heymann nephritis pathogenic epitope (amino acids 1-86). Direct binding studies (ligand blotting, affinity chromatography, density-gradient sedimentation) using fusion proteins representing overlapping RAP domains; radiolabeled heparin binding assays Proceedings of the National Academy of Sciences of the United States of America High 7512726
1993 In renal proximal tubule cells, alpha2-MRAP (LRPAP1) is located predominantly in the rough endoplasmic reticulum (RER). Alpha2-MRAP-binding sites are present on gp330 at the proximal tubule brush border. The apparent brush border localization seen in snap-frozen sections is artifactual, resulting from release of RER-resident LRPAP1 during tissue processing and subsequent binding to cell-surface gp330. Immunocytochemistry with specific anti-alpha2-MRAP antibodies on PLP-fixed vs. snap-frozen rat kidney sections; alpha2-MRAP-IgG fusion protein binding assays; controlled incubation experiments showing redistribution artifact European journal of cell biology High 8223699
1995 RAP (LRPAP1) functions as a molecular chaperone assisting in the folding of megalin (gp330) in the endoplasmic reticulum and its transport to the cell surface, while also acting as a universal inhibitor of ligand binding to LDL receptor family members at the cell surface. Review synthesizing biochemical, immunocytochemical, and functional data from the field; primary experimental evidence includes co-purification, ligand binding inhibition assays, and ER localization studies Journal of the American Society of Nephrology : JASN Medium 7579068
1996 RAP (LRPAP1) binds calmodulin in a Ca2+- and pH-dependent manner and is a substrate for calmodulin-dependent kinase II (CaM-kinase II), which phosphorylates serine residues in RAP domains D2 (amino acids 113-218) and D3 (amino acids 219-323). Calcineurin dephosphorylates RAP. RAP is also phosphorylated by casein kinase II, and phosphorylation of RAP in vivo was demonstrated in 32P-labeled cell cultures. Calmodulin binding assays; in vitro kinase assays with CaM-kinase II and casein kinase II; phosphatase (calcineurin) assays; 32P-labeling of cell cultures to demonstrate in vivo phosphorylation; domain mapping with D2 and D3 fragments The EMBO journal High 8861945
2001 RAP (LRPAP1) serves as a molecular chaperone/escort protein for LDL receptor family members in the endoplasmic reticulum, preventing premature ligand interactions during receptor transport through the secretory pathway, and also promotes proper receptor folding independently of its ligand-inhibitory function. Review of experimental evidence including co-purification, ligand binding inhibition assays, secretory pathway transport studies, and ER localization experiments from multiple labs International review of cytology Medium 11580203
2004 RAP (LRPAP1) crosses the blood-brain barrier via a saturable transport system, with megalin (LRP2) mediating most apical-to-basolateral transcytosis across polarized epithelial cells. Approximately 70% of blood-borne RAP reaches brain parenchyma (not just vasculature). Transport is inhibitable by excess RAP, confirming receptor-mediated transcytosis. Pharmacokinetic studies with [125I]-RAP in intact mice; in situ brain perfusion; capillary depletion of brain homogenates; transport assays in stably transfected MDCK cells expressing megalin Journal of cell science High 15383619
2007 The three-dimensional structure of RAP (LRPAP1) consists of three independent three-helix bundles (domains 1, 2, and 3) connected by long, flexible linkers. This architecture allows RAP to adopt various conformations when interacting with LDL receptor family members. NMR spectroscopy to determine domain 2 structure; small-angle neutron scattering (SANS) combined with simulated annealing protocol to characterize overall RAP architecture Protein science : a publication of the Protein Society High 17656581
2001 RAP (LRPAP1) inhibits transthyretin (TTR) internalization in hepatocytes, and the ~90 kDa TTR-receptor complex is RAP-sensitive, indicating that TTR is internalized via an as-yet unidentified LDL receptor family member in liver cells. This RAP-sensitive pathway was confirmed in both hepatoma cell lines and primary hepatocytes. Uptake competition assays with RAP; chemical cross-linking of [125I]-TTR to identify receptor complex; primary hepatocyte and hepatoma cell line comparison; lipid-deficient serum controls The Journal of biological chemistry Medium 11278770
1996 RAP (LRPAP1) mediates RAP-sensitive and proteoglycan-mediated pathways of lipoprotein lipase (LPL) degradation in adipocytes. The RAP-sensitive (LRP-mediated) component accounts for 30-54% of LPL degradation at 1 h, diminishing to 19-23% at 4 h, while heparan sulfate proteoglycans mediate the major non-RAP-sensitive fraction. 125I-LPL degradation assays in BFC-1β adipocytes with RAP inhibition; heparinase/heparitinase treatment; phosphatidylinositol-specific phospholipase C treatment; 35SO4 proteoglycan labeling to measure turnover kinetics Journal of lipid research Medium 8978495
2012 RAP (LRPAP1) treatment of neurons potentiates the inhibitory effects of full-length APP on axonal outgrowth, and RAP-LRP binding stimulates axon growth independently of APP, associated with ERK2 activation. This demonstrates that LRPAP1 engagement of LRP has APP-independent signaling consequences in neurons. Neurite outgrowth measurements in wild-type vs. APP knockout neurons treated with sAPPα and/or RAP; ERK2 activation measured; 1 day in vitro cultures Journal of neurochemistry Medium 23061396
2023 Secreted LRPAP1 binds the extracellular domain of IFNAR1 (interferon alpha/beta receptor 1) via its N-terminus, triggering IFNAR1 ubiquitination and degradation, thereby suppressing interferon signaling and facilitating viral immune evasion. Viral proteases (SARS-CoV-2 3CLpro and EV71 2Apro) upregulate LRPAP1 expression and secretion to exploit this mechanism. A small N-terminal LRPAP1 peptide recapitulates IFNAR1 degradation, and α2M (a LRPAP1 inhibitor) stabilizes IFNAR1 and arrests viral infections. Binding assays between secreted LRPAP1 and IFNAR1 extracellular domain; ubiquitination and degradation assays in vitro, ex vivo (mouse brain), and in vivo (newborn mice); viral infection assays with multiple viruses (HSV-1, HBV, EV71, HCoV-OC43); N-terminal peptide experiments; α2M inhibition experiments; protease upregulation assays Signal transduction and targeted therapy High 37743411
2022 Loss of lrpap1 in zebrafish (CRISPR/Cas9 frameshift mutation) causes myopia with increased axial length and disordered scleral collagen fibers. The mechanism involves activation of TGF-β signaling and increased apoptosis. TGF-β agonist treatment of wild-type embryos recapitulates the apoptosis phenotype, while TGF-β inhibitor treatment mitigates apoptosis in lrpap1 mutants, establishing TGF-β-induced apoptosis as the downstream pathway. CRISPR/Cas9-generated zebrafish lrpap1 knockout; refractive error measurement; transmission electron microscopy of scleral collagen; RNA sequencing and bioinformatics; acridine orange and TUNEL staining; TGF-β agonist and inhibitor rescue experiments Cell communication and signaling : CCS High 36261846
1994 The human LRPAP1 gene was chromosomally mapped to the short arm of chromosome 4 at position 4p16.3, in the region of the chromosomal deletion causing Wolf-Hirschhorn syndrome, by fluorescence in situ hybridization. Fluorescence in situ hybridization (FISH) using human RAP cDNA probe Genomics Medium 7959795
2014 A homozygous frameshift mutation in LRPAP1 (c.199delC, p.Q67Sfs*8) co-segregates with early-onset high myopia in a consanguineous family, providing genetic evidence that LRPAP1 loss-of-function causes autosomal recessive high myopia. Whole exome sequencing of 298 early-onset high myopia patients; Sanger sequencing confirmation; co-segregation analysis in family members; absence in 192 healthy controls Investigative ophthalmology & visual science Medium 25525168
2018 LRPAP1 acts as a B-cell receptor (BCR) antigen that induces proliferation via BCR pathway activation in a subset of mantle cell lymphomas (MCL). An LRPAP1-ETA' toxin conjugate specifically kills MCL cells bearing LRPAP1-specific BCRs, demonstrating that LRPAP1-BCR interaction drives chronic autoantigenic BCR signaling. Recombinant expression of BCRs from 21 MCL patients and 7 cell lines; antigen screening; LRPAP1 stimulation of BCR pathway activation; LRPAP1-ETA' immunotoxin killing assays; serum antibody characterization Leukemia Medium 29955130

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Ras and Rap control AMPA receptor trafficking during synaptic plasticity. Cell 648 12202034
2005 Linking Rap to cell adhesion. Current opinion in cell biology 389 15780587
1998 A Rap guanine nucleotide exchange factor enriched highly in the basal ganglia. Proceedings of the National Academy of Sciences of the United States of America 294 9789079
2001 A new phospholipase-C-calcium signalling pathway mediated by cyclic AMP and a Rap GTPase. Nature cell biology 285 11715024
1996 Ras/Rap effector specificity determined by charge reversal. Nature structural biology 186 8756332
1995 The Heymann nephritis antigenic complex: megalin (gp330) and RAP. Journal of the American Society of Nephrology : JASN 183 7579068
2004 Putting the rap on Akt. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 178 15483033
2003 Does Rap1 deserve a bad Rap? Trends in biochemical sciences 171 12765839
2008 Specificity in Ras and Rap signaling. The Journal of biological chemistry 149 19091745
2003 The extracellular Phr peptide-Rap phosphatase signaling circuit of Bacillus subtilis. Frontiers in bioscience : a journal and virtual library 138 12456319
2012 Plexins are GTPase-activating proteins for Rap and are activated by induced dimerization. Science signaling 137 22253263
2010 Ras and Rap signaling in synaptic plasticity and mental disorders. The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry 127 20431046
2008 Epac/Rap and PKA are novel mechanisms of ANP-induced Rac-mediated pulmonary endothelial barrier protection. Journal of cellular physiology 126 18064650
2011 Regulating Rap small G-proteins in time and space. Trends in cell biology 125 21820312
2003 The Rap GTPases regulate integrin-mediated adhesion, cell spreading, actin polymerization, and Pyk2 tyrosine phosphorylation in B lymphocytes. The Journal of biological chemistry 118 14701796
2001 The roles of receptor-associated protein (RAP) as a molecular chaperone for members of the LDL receptor family. International review of cytology 110 11580203
2004 Efficient transfer of receptor-associated protein (RAP) across the blood-brain barrier. Journal of cell science 109 15383619
2004 ARAP3 is a PI3K- and rap-regulated GAP for RhoA. Current biology : CB 104 15296756
2011 Rap-linked cAMP signaling Epac proteins: compartmentation, functioning and disease implications. Cellular signalling 102 21402149
1991 The residues of Ras and Rap proteins that determine their GAP specificities. The Journal of biological chemistry 102 1828804
1997 Mouse CD-RAP/MIA gene: structure, chromosomal localization, and expression in cartilage and chondrosarcoma. Developmental dynamics : an official publication of the American Association of Anatomists 100 9097023
2014 Detection of mutations in LRPAP1, CTSH, LEPREL1, ZNF644, SLC39A5, and SCO2 in 298 families with early-onset high myopia by exome sequencing. Investigative ophthalmology & visual science 94 25525168
2005 The G alpha(o/i)-coupled cannabinoid receptor-mediated neurite outgrowth involves Rap regulation of Src and Stat3. The Journal of biological chemistry 92 16046413
1997 The rap and hor proteins of Erwinia, Serratia and Yersinia: a novel subgroup in a growing superfamily of proteins regulating diverse physiological processes in bacterial pathogens. Molecular microbiology 92 9402023
1998 RAP, a novel type of ER chaperone. Trends in cell biology 90 9714598
2000 RAP, RAP, open up! New wrinkles for RAP1 in yeast. Trends in genetics : TIG 89 10652526
2011 Requirement for Plk2 in orchestrated ras and rap signaling, homeostatic structural plasticity, and memory. Neuron 83 21382555
2008 The rap GTPases regulate B cell morphology, immune-synapse formation, and signaling by particulate B cell receptor ligands. Immunity 81 18191594
2001 Identification and characterization of RA-GEF-2, a Rap guanine nucleotide exchange factor that serves as a downstream target of M-Ras. The Journal of biological chemistry 80 11524421
2020 Genetic modulation of RAP alters fruit coloration in both wild and cultivated strawberry. Plant biotechnology journal 75 31845477
2015 RNA antisense purification (RAP) for mapping RNA interactions with chromatin. Methods in molecular biology (Clifton, N.J.) 74 25555582
1998 Electrostatic contributions to protein-protein binding affinities: application to Rap/Raf interaction. Proteins 73 9533625
1997 Complete cDNA sequence and tissue localization of N-RAP, a novel nebulin-related protein of striated muscle. Cell motility and the cytoskeleton 73 9295142
2006 GAP1 family members constitute bifunctional Ras and Rap GTPase-activating proteins. The Journal of biological chemistry 68 16431904
2005 Trading spaces: Rap, Rac, and Rho as architects of transendothelial migration. Current opinion in hematology 65 15604886
1994 Functional domains of the receptor-associated protein (RAP). Proceedings of the National Academy of Sciences of the United States of America 64 7512726
1998 Receptor-associated protein (RAP): a specialized chaperone for endocytic receptors. Biological chemistry 63 9792434
1991 Phosphorylation of a Ras-related GTP-binding protein, Rap-1b, by a neuronal Ca2+/calmodulin-dependent protein kinase, CaM kinase Gr. Proceedings of the National Academy of Sciences of the United States of America 62 1901412
2018 Ras and Rap Signal Bidirectional Synaptic Plasticity via Distinct Subcellular Microdomains. Neuron 61 29706584
2001 Internalization of transthyretin. Evidence of a novel yet unidentified receptor-associated protein (RAP)-sensitive receptor. The Journal of biological chemistry 60 11278770
2007 A Wnt-CKIvarepsilon-Rap1 pathway regulates gastrulation by modulating SIPA1L1, a Rap GTPase activating protein. Developmental cell 58 17336901
2015 RAP: RNA-Seq Analysis Pipeline, a new cloud-based NGS web application. BMC genomics 55 26046471
2013 Conformational change-induced repeat domain expansion regulates Rap phosphatase quorum-sensing signal receptors. PLoS biology 54 23526881
2007 Identification of three novel proteins (SGSM1, 2, 3) which modulate small G protein (RAP and RAB)-mediated signaling pathway. Genomics 54 17509819
2000 Role of rap in the biogenesis of lipoprotein receptors. Trends in cardiovascular medicine 54 11239794
1993 Location of gp330/alpha 2-m receptor-associated protein (alpha 2-MRAP) and its binding sites in kidney: distribution of endogenous alpha 2-MRAP is modified by tissue processing. European journal of cell biology 52 8223699
2008 cAMP-induced Epac-Rap activation inhibits epithelial cell migration by modulating focal adhesion and leading edge dynamics. Cellular signalling 51 18346875
2006 Differential and brain region-specific regulation of Rap-1 and Epac in depressed suicide victims. Archives of general psychiatry 50 16754837
2003 Organization, transcription, and expression of rhoptry associated protein genes in the Babesia bigemina rap-1 locus. Molecular and biochemical parasitology 49 12672519
2003 New N-RAP-binding partners alpha-actinin, filamin and Krp1 detected by yeast two-hybrid screening: implications for myofibril assembly. Journal of cell science 49 12692149
2008 A novel Epac-Rap-PP2A signaling module controls cAMP-dependent Akt regulation. The Journal of biological chemistry 48 18550542
2011 Prostaglandin E2 regulates renal cell carcinoma invasion through the EP4 receptor-Rap GTPase signal transduction pathway. The Journal of biological chemistry 46 21832044
2001 Ultrastructural and biochemical localization of N-RAP at the interface between myofibrils and intercalated disks in the mouse heart. Biochemistry 46 11732910
2010 RapGAPs in brain: multipurpose players in neuronal Rap signalling. The European journal of neuroscience 44 20576033
2005 The NO/cGMP pathway inhibits Rap 1 activation in human platelets via cGMP-dependent protein kinase I. Thrombosis and haemostasis 44 15711749
2002 Ultrastructural cartilage abnormalities in MIA/CD-RAP-deficient mice. Molecular and cellular biology 44 11839810
2011 Epac-Rap signaling reduces cellular stress and ischemia-induced kidney failure. Journal of the American Society of Nephrology : JASN 42 21493776
2007 RAP-1 and the RAL-1/exocyst pathway coordinate hypodermal cell organization in Caenorhabditis elegans. The EMBO journal 42 17989692
2001 Variation in the LRP-associated protein gene (LRPAP1) is associated with late-onset Alzheimer disease. American journal of medical genetics 42 11425005
1994 Chromosomal localization of human genes for the LDL receptor family member glycoprotein 330 (LRP2) and its associated protein RAP (LRPAP1). Genomics 42 7959795
2010 A Rap/phosphatidylinositol 3-kinase pathway controls pseudopod formation [corrected]. Molecular biology of the cell 41 20089846
1994 gp330 and RAP: the Heymann nephritis antigenic complex. Annals of the New York Academy of Sciences 41 7944157
2014 The Ras/Rap GTPase activating protein RASA3: from gene structure to in vivo functions. Advances in biological regulation 38 25294679
2006 The Rap GTPases mediate CXCL13- and sphingosine1-phosphate-induced chemotaxis, adhesion, and Pyk2 tyrosine phosphorylation in B lymphocytes. European journal of immunology 38 16821235
2018 RAP GTPases and platelet integrin signaling. Platelets 37 29863951
2005 The Rap-B-Raf signalling pathway is activated by glucose and glucagon-like peptide-1 in human islet cells. Diabetologia 37 15995848
2017 Development of RAP Tag, a Novel Tagging System for Protein Detection and Purification. Monoclonal antibodies in immunodiagnosis and immunotherapy 35 28339303
2007 The Rap GTPase activator Drosophila PDZ-GEF regulates cell shape in epithelial migration and morphogenesis. Molecular and cellular biology 35 17846121
2006 Targeted disruption of N-RAP gene function by RNA interference: a role for N-RAP in myofibril organization. Cell motility and the cytoskeleton 32 16767749
2007 Optimal expression condition of recombinant RAP. Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban 31 17393096
2014 RAP-011, an activin receptor ligand trap, increases hemoglobin concentration in hepcidin transgenic mice. American journal of hematology 30 25236856
1994 Interstrain conservation of babesial RAP-1 surface-exposed B-cell epitopes despite rap-1 genomic polymorphism. Infection and immunity 30 7518810
2009 Myofibril assembly visualized by imaging N-RAP, alpha-actinin, and actin in living cardiomyocytes. Experimental cell research 29 19233165
2004 G-protein-coupled receptor-mediated activation of rap GTPases: characterization of a novel Galphai regulated pathway. Oncogene 29 14712229
2017 The role of small GTPases and EPAC-Rap signaling in the regulation of the blood-brain and blood-retinal barriers. Tissue barriers 28 28632993
2008 Spa-1 (Sipa1) and Rap signaling in leukemia and cancer metastasis. Cancer science 28 19037996
2021 Epac-1/Rap-1 signaling pathway orchestrates the reno-therapeutic effect of ticagrelor against renal ischemia/reperfusion model. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 27 33957564
2000 Myofibrillogenesis and formation of cell contacts mediate the localization of N-RAP in cultured chick cardiomyocytes. Cell motility and the cytoskeleton 27 11002311
1996 The receptor-associated protein (RAP) binds calmodulin and is phosphorylated by calmodulin-dependent kinase II. The EMBO journal 27 8861945
2014 APOE and LRPAP1 gene polymorphism and risk of Parkinson's disease. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 26 24504617
2013 Rap G protein signal in normal and disordered lymphohematopoiesis. Experimental cell research 26 23603280
2010 Enhanced cartilage regeneration in MIA/CD-RAP deficient mice. Cell death & disease 26 21368873
2018 LRPAP1 is a frequent proliferation-inducing antigen of BCRs of mantle cell lymphomas and can be used for specific therapeutic targeting. Leukemia 24 29955130
2008 Expression and alternative splicing of N-RAP during mouse skeletal muscle development. Cell motility and the cytoskeleton 24 18792955
2018 Vascular Endothelial Growth Factor-A Exerts Diverse Cellular Effects via Small G Proteins, Rho and Rap. International journal of molecular sciences 23 29659486
2018 How Rap and its GEFs control liver physiology and cancer development. C3G alterations in human hepatocarcinoma. Hepatic oncology 23 30302196
2006 Association of low density lipoprotein receptor related protein-associated protein (LRPAP1) gene insertion/deletion polymorphism with gallstone disease. Journal of gastroenterology and hepatology 23 16704534
2005 rap gene encodes Fizzy-related protein (Fzr) and regulates cell proliferation and pattern formation in the developing Drosophila eye-antennal disc. Developmental biology 23 16098963
1989 Expression of the ras-related rap genes in human tumors. International journal of cancer 23 2514150
2023 Secreted LRPAP1 binds and triggers IFNAR1 degradation to facilitate virus evasion from cellular innate immunity. Signal transduction and targeted therapy 22 37743411
2014 Epac, Rap and Rab3 act in concert to mobilize calcium from sperm's acrosome during exocytosis. Cell communication and signaling : CCS 22 25159528
2010 Evidence for negative selection on the gene encoding rhoptry-associated protein 1 (RAP-1) in Plasmodium spp. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 22 20363375
2008 LRP-associated protein gene (LRPAP1) and susceptibility to degenerative dementia. Genes, brain, and behavior 22 18721259
2007 Rac and Rap GTPase activation assays. Methods in molecular biology (Clifton, N.J.) 22 18453105
1996 RAP kinase, a new enzyme phosphorylating the acidic P proteins from Saccharomyces cerevisiae. Biochimica et biophysica acta 22 8620032
1996 Lipoprotein lipase degradation by adipocytes: receptor-associated protein (RAP)-sensitive and proteoglycan-mediated pathways. Journal of lipid research 22 8978495
2022 Lrpap1 deficiency leads to myopia through TGF-β-induced apoptosis in zebrafish. Cell communication and signaling : CCS 21 36261846
2012 APP independent and dependent effects on neurite outgrowth are modulated by the receptor associated protein (RAP). Journal of neurochemistry 21 23061396
2007 The structure of receptor-associated protein (RAP). Protein science : a publication of the Protein Society 21 17656581
2005 N-RAP expression during mouse heart development. Developmental dynamics : an official publication of the American Association of Anatomists 21 15765519

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