Affinage

LDLRAP1

Low density lipoprotein receptor adapter protein 1 · UniProt Q5SW96

Length
308 aa
Mass
33.9 kDa
Annotated
2026-06-10
64 papers in source corpus 20 papers cited in narrative 20 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LDLRAP1 (ARH) is a modular clathrin-associated endocytic adaptor that bridges FXNPXY-motif cargo to the clathrin coat, governing receptor internalization and trafficking in a cell-type-specific manner (PMID:12221107, PMID:16179341). Its N-terminal PTB domain binds the NPVY/FXNPXY internalization sequence in the cytoplasmic tail of the LDL receptor and related superfamily receptors including megalin, LRP1, and LRP8, while a C-terminal region simultaneously engages purified clathrin via an LLDLE clathrin-box and the beta2-adaptin appendage of AP-2; both the PTB domain and one of these coat-binding contacts are required to cluster LDLR into coated pits and drive LDL internalization (PMID:12221107, PMID:12451172, PMID:16179341, PMID:14528014, PMID:17727637). In hepatocytes and lymphocytes ARH is obligatory for LDLR endocytosis, whereas in fibroblasts and HeLa cells it is functionally redundant with Dab2 and, when acting alone, depends on AP-2 (PMID:15166224, PMID:16984970); combined loss of Arh and Dab2 in mice produces hypercholesterolemia equivalent to LDLR knockout, establishing the two adaptors as the principal mediators of LDLR-driven cholesterol homeostasis (PMID:27005486). ARH function is post-translationally tuned: S-nitrosylation at C199/C286 is required for AP-2 association and LDL uptake, and Ser14 is phosphorylated during G2/M (PMID:21778424, PMID:23564733). Beyond endocytosis, ARH cooperates with the epithelial adaptor AP-1B in basolateral exocytic sorting of LDLR from recycling endosomes (PMID:21444685), localizes to mitotic structures and centrosomes where its loss impairs centrosome assembly and cytokinesis (PMID:18417616, PMID:21778424), and controls endocytosis of the potassium channels ROMK and BKα in the renal distal nephron to maintain potassium homeostasis (PMID:19841541, PMID:41138214).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2002 High

    Established the molecular basis of ARH as an endocytic adaptor by showing its PTB domain reads the LDLR internalization signal while a distinct C-terminal region recruits the clathrin coat.

    Evidence In vitro pull-down and binding assays with Kd measurement plus mutagenesis of the LDLR NPVY motif, clathrin-box, and beta2-adaptin appendage, with colocalization in HeLa cells

    PMID:12221107 PMID:12451172

    Open questions at the time
    • Stoichiometry and order of clathrin vs AP-2 engagement not resolved
    • Structural model of the tripartite bridge not defined
  2. 2003 High

    Extended ARH cargo recognition beyond LDLR to other LDLR-superfamily receptors and demonstrated a functional role across the full endocytic-recycling itinerary.

    Evidence Yeast two-hybrid, pull-down, co-IP, colocalization, and 125I-lactoferrin uptake assays for megalin in MDCK cells

    PMID:14528014

    Open questions at the time
    • Whether ARH actively drives recycling or passively accompanies cargo unclear
  3. 2004 High

    Defined the in vivo requirement for ARH in LDLR endocytosis and revealed an additional role in stabilizing LDL-LDLR association within pits.

    Evidence Electron microscopy quantification and biochemical binding assays in ARH-deficient vs normal lymphocytes

    PMID:15166224

    Open questions at the time
    • Molecular basis of the LDL-binding stabilization defect not defined
  4. 2005 High

    Showed in polarized hepatocytes that ARH must simultaneously contact cargo and a coat component, and quantified the magnitude of ARH dependence for LDL uptake.

    Evidence Domain mutagenesis with cell-based clustering assays in WIF-B cells, adenoviral rescue in Arh-/- mouse liver, and RNAi in HepG2 cells

    PMID:16129683 PMID:16179341

    Open questions at the time
    • Trigger for ARH recruitment upon endocytosis activation not identified
  5. 2006 High

    Resolved the cell-type-specific redundancy of ARH by epistasis with Dab2, explaining why ARH is essential in some tissues but dispensable in others.

    Evidence Single and double siRNA knockdown of Dab2 and ARH with LDL uptake and clustering readouts in HeLa cells and fibroblasts

    PMID:16984970

    Open questions at the time
    • Determinants of tissue-specific reliance on ARH vs Dab2 not defined at the molecular level
  6. 2008 Medium

    Uncovered an unexpected mitotic and centrosomal role for ARH beyond endocytosis.

    Evidence Co-IP, centrosome fractionation, mitotic immunofluorescence, and Arh-/- MEF phenotype analysis

    PMID:18417616

    Open questions at the time
    • Direct vs indirect basis of centrosome/cytokinesis defects unresolved
    • Single lab
  7. 2009 High

    Broadened ARH cargo to ion channels, identifying a variant endocytic signal and an in vivo role in renal potassium handling.

    Evidence Direct binding, co-IP, siRNA endocytosis assay in COS-7, kidney colocalization, and Arh-/- mice under dietary potassium challenge

    PMID:19841541

    Open questions at the time
    • How ARH recognizes the divergent YxNPxFV signal vs canonical FXNPXY not structurally defined
  8. 2011 Medium

    Defined post-translational control and a directional exocytic function: cdc2-dependent Ser14 phosphorylation during mitosis and AP-1B-dependent basolateral delivery of LDLR.

    Evidence Mass spectrometry phosphosite mapping, kinase inhibitor and KO/patient fibroblast analysis, and ARH-AP-1B interface mutagenesis with sorting assays in polarized MDCK cells

    PMID:21444685 PMID:21778424

    Open questions at the time
    • Functional consequence of Ser14 phosphorylation on endocytic activity not directly tested
    • Single labs for each finding
  9. 2013 High

    Identified S-nitrosylation as a redox switch gating ARH-AP-2 association and pathway-specific LDL uptake.

    Evidence S-nitrosylation site identification, NOS inhibition, Cys mutagenesis, AP-2 co-IP, and LDL uptake assays with Dab2/VLDL controls

    PMID:23564733

    Open questions at the time
    • NOS isoform and physiological signals driving nitrosylation unknown
    • Single lab
  10. 2014 Medium

    Established the selectivity of the ARH/Dab2 adaptor module for the LDLR pathway versus the Numb-NPC1L1 pathway.

    Evidence Binding assays and individual siRNA knockdowns with LDL and cholesterol uptake readouts in hepatocyte and intestinal models

    PMID:25331956

    Open questions at the time
    • Molecular determinant of cargo selectivity not defined
  11. 2016 High

    Demonstrated through double-knockout genetics that ARH and Dab2 together account for the majority of LDLR adaptor function in whole-body cholesterol homeostasis.

    Evidence Arh-/-;Dab2-/- mice with serum cholesterol, HMG-CoA reductase blotting, and cell-type-specific expression analysis

    PMID:27005486

    Open questions at the time
    • Mechanism by which endothelial Dab2 regulates hepatocyte HMG-CoA reductase not defined
  12. 2022 Medium

    Linked LDLRAP1 loss to insulin resistance and adipose dysfunction, expanding its physiological role beyond cholesterol clearance.

    Evidence LDLRAP1-/- mouse with metabolic phenotyping, glucose uptake, AKT phosphorylation, and adipose gene expression analysis

    PMID:35460615

    Open questions at the time
    • Direct molecular link between ARH and AKT/insulin signaling not established
    • Single lab
  13. 2025 High

    Generalized ARH-dependent channel endocytosis to BKα and clarified renal potassium handling with sex-specific compensation.

    Evidence Co-IP of ARH and BKα and immunoblotting/channel localization in ARH-KO vs WT renal cortex under dietary potassium challenge

    PMID:41138214

    Open questions at the time
    • Reciprocal validation of the BKα interaction beyond co-IP not shown
  14. 2026 Medium

    Identified ARH as a druggable target whose LDLR-binding interface can be covalently disrupted to block coronavirus infection.

    Evidence Activity-based proteome profiling, competitive ABPP, LC-MS/MS, and fluorescence polarization with a covalent probe modifying C119

    PMID:41734033

    Open questions at the time
    • Mechanistic role of the LDLR-ARH interaction in viral entry not defined
    • Single study

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ARH's distinct activities — endocytosis, basolateral exocytosis, mitotic/centrosomal function, and metabolic signaling — are integrated and differentially regulated within a single cell remains unresolved.
  • No structural model of the multivalent cargo/clathrin/AP-2 complex
  • Signals coordinating PTM-based switching across roles unknown
  • Direct molecular basis of non-endocytic functions undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0038024 cargo receptor activity 3 GO:0008289 lipid binding 1
Localization
GO:0005635 nuclear envelope 2 GO:0005768 endosome 2 GO:0005886 plasma membrane 2 GO:0031410 cytoplasmic vesicle 2 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-1430728 Metabolism 2 R-HSA-1640170 Cell Cycle 2 R-HSA-9609507 Protein localization 1
Partners
AP1BAP2B1CLTCDAB2LDLRLRP1LRP2ROMK
Complex memberships
clathrin-coated pit

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 The PTB domain of ARH/LDLRAP1 binds directly to the NPVY internalization sequence in the cytoplasmic tail of the LDL receptor in a sequence-specific manner; mutations in NPVY that impair LDLR internalization also abolish ARH binding. ARH also binds purified clathrin (Kd ~44 nM) via a canonical clathrin-box sequence (LLDLE) mapping to the clathrin heavy chain N-terminal domain, and binds the beta2-adaptin subunit of AP-2 via a conserved 20-aa C-terminal region. Pull-down assays, in vitro binding, mutagenesis of LDLR internalization motif and beta2-adaptin appendage domain The Journal of biological chemistry High 12221107
2002 ARH/LDLRAP1 binds directly to soluble clathrin trimers and to the independently folded appendage domain of the beta-adaptin subunit of clathrin adaptors; ARH also binds phosphoinositides. At steady state, ARH colocalizes with endocytic proteins in HeLa cells, and the LDL receptor traffics through peripheral ARH-positive sites before delivery to early endosomes. Pull-down, colocalization by fluorescence microscopy, phosphoinositide binding assay Proceedings of the National Academy of Sciences of the United States of America High 12451172
2005 In polarized hepatocytes (WIF-B cells) and in Arh−/− mouse livers rescued with recombinant ARH, the intact FDNPVY sequence in the LDLR tail is required for ARH-associated receptor clustering into clathrin-coated pits. The PTB domain of ARH plus either the clathrin-box or the AP-2 binding region are both required for LDLR clustering and LDL internalization, establishing that ARH must simultaneously contact LDLR and either clathrin or AP-2. Mutagenesis of ARH domains, cell-based LDLR clustering assay in WIF-B polarized hepatocytes, in vivo adenoviral rescue in Arh−/− mice, quantitative immunofluorescence The Journal of biological chemistry High 16179341
2004 In ARH-deficient lymphocytes, LDLRs accumulate predominantly on the plasma membrane outside clathrin-coated pits (>27-fold excess), yet the number of LDLRs within coated pits is similar to normal cells. ARH is required not only for LDLR internalization but also for efficient LDL binding and for stabilizing LDL–LDLR association within invaginating pits. Electron microscopy quantification of LDLR distribution, biochemical binding assays in ARH−/− vs. normal lymphocytes The Journal of biological chemistry High 15166224
2003 ARH/LDLRAP1 binds the first FXNPXY motif of megalin (an endocytic receptor of the LDL receptor superfamily) as shown by yeast two-hybrid, pull-down, and co-immunoprecipitation. ARH colocalizes with megalin in clathrin-coated pits and in recycling endosomes. Expression of ARH in MDCK cells enhances megalin-mediated uptake of 125I-lactoferrin, and ARH escorts megalin sequentially through clathrin-coated pits, early endosomes, and tubular recycling endosomes back to the cell surface. Yeast two-hybrid, pull-down, co-immunoprecipitation, fluorescence colocalization, 125I-lactoferrin uptake assay, nocodazole perturbation Molecular biology of the cell High 14528014
2005 In HepG2 hepatocytes, ARH is recruited to the basolateral membrane upon LDLR-mediated endocytosis activation (not merely LDL binding). RNAi-mediated depletion of ARH (>70%) caused ~80% reduction in LDL internalization. ARH co-distributes with LDLR on the basolateral surface and associates with other endocytic machinery proteins. RNA interference, quantitative immunofluorescence, immunofluorescence colocalization in polarized HepG2 cells The Journal of biological chemistry Medium 16129683
2006 In HeLa cells and fibroblasts, ARH is dispensable for LDL uptake when Dab2 is present; when Dab2 is absent, ARH can mediate LDLR endocytosis but requires AP-2. Dab2 efficiently clusters LDLRs into coated pits, whereas ARH may accelerate later steps in cooperation with AP-2. ARH action requires AP-2 in the absence of Dab2. siRNA knockdown of Dab2 and ARH individually and in combination, LDL uptake assays, LDLR coated-pit clustering analysis in HeLa cells and fibroblasts Journal of cell science High 16984970
2008 ARH/LDLRAP1 associates with centrosomal proteins (gamma-tubulin, GPC2, GPC3) and motor proteins (dynein heavy and intermediate chains). ARH co-fractionates with gamma-tubulin on isolated centrosomes. During mitosis, ARH sequentially localizes to the nuclear membrane, kinetochores, spindle poles, and midbody. Arh−/− MEFs show absent or smaller centrosomes and exhibit slower growth and prolonged cytokinesis. Co-immunoprecipitation, subcellular fractionation of isolated centrosomes, immunofluorescence during mitosis, siRNA knockdown in Rat-1 fibroblasts, Arh−/− MEF phenotype analysis Molecular biology of the cell Medium 18417616
2009 ARH/LDLRAP1 binds directly to ROMK (renal outer medullary potassium channel) via a variant endocytic signal YxNPxFV in ROMK's cytoplasmic domain and recruits ROMK to clathrin-coated pits. ARH knockdown decreased basal ROMK endocytosis in COS-7 cells. In mouse kidney, ARH co-immunoprecipitates and colocalizes with ROMK in the distal nephron; ARH protein abundance is modulated inversely by dietary potassium relative to ROMK levels; Arh−/− mice show altered ROMK response to potassium intake. Direct binding assay, co-immunoprecipitation, siRNA knockdown, endocytosis assay in COS-7 cells, co-localization in kidney sections, Arh−/− mouse model with dietary potassium challenge The Journal of clinical investigation High 19841541
2010 ARH/LDLRAP1 binds both FXNPXF signals in the cytosolic domain of amnionless (AMN), the membrane-anchoring subunit of the cubam receptor complex (cubilin–amnionless). Yeast two-hybrid combined with sequential mutagenesis showed that both signals are functionally redundant and each can direct cubam endocytosis through ARH or Dab2. Yeast two-hybrid, sequential mutagenesis of AMN FXNPXF motifs, expression of AMN mutant panel in cells Traffic (Copenhagen, Denmark) Medium 20088845
2011 ARH cooperates with the epithelial-specific adaptor AP-1B in basolateral exocytosis of LDLR from recycling endosomes. ARH and AP-1B co-localize in recycling endosomes. Knockdown of ARH in polarized epithelial cells causes apical missorting of LDLR-CT27 (a truncated LDLR encoding only the FxNPxY motif). A mutation in ARH designed to disrupt its interaction with AP-1B specifically blocks exocytosis of LDLR-CT27. siRNA knockdown, mutagenesis of ARH–AP-1B interface, immunofluorescence colocalization in polarized MDCK cells, LDLR mis-sorting assay The Journal of cell biology High 21444685
2011 ARH protein is phosphorylated during G2/M phase by a roscovitine-sensitive kinase (likely cdc2/CDK1) at Ser14 (identified by mass spectrometry). ARH localizes to mitotic microtubules, lamin B1 on the nuclear envelope, and clathrin heavy chain on mitotic spindles. Cells lacking ARH show disfigured nuclei and defective mitotic spindles and undergo premature senescence (elevated p16, γ-H2AX foci). The W22X ARH mutant (which produces protein starting at Met46, lacking Ser14) shows the most severe mitotic defects. Mass spectrometry identification of phosphorylation site, roscovitine kinase inhibitor treatment, immunofluorescence localization to mitotic structures, siRNA knockdown in IMR90 cells, analysis of ARH−/− patient fibroblasts Arteriosclerosis, thrombosis, and vascular biology Medium 21778424
2013 Nitric oxide S-nitrosylates ARH at cysteines C199 and C286; these modifications are required for ARH to associate with the AP-2 component of clathrin-coated pits and to support LDL uptake. Inhibition of nitric oxide synthase impairs ARH-supported LDL uptake but does not affect dab2-supported LDL uptake or VLDL remnant uptake, demonstrating specificity for the ARH pathway. S-nitrosylation assay identifying C199 and C286, NOS inhibitor treatment, mutagenesis of Cys residues, LDL uptake assay, AP-2 co-immunoprecipitation Journal of lipid research High 23564733
2014 ARH and Dab2 each participate in LDLR endocytosis but not in NPC1L1 endocytosis: ARH and Dab2 do not bind NPC1L1 and are not required for NPC1L1 internalization. Conversely, Numb (which mediates NPC1L1 endocytosis) does not interact with the LDLR C-terminus and is dispensable for LDL uptake, establishing that ARH/Dab2 selectively regulate the LDLR pathway. Binding assays (pull-down), siRNA knockdown of ARH, Dab2, and Numb individually, LDL and cholesterol uptake assays in hepatocyte and intestinal cell models The Journal of biological chemistry Medium 25331956
2016 Combined deletion of both Arh and Dab2 in mice produces profound hypercholesterolemia equivalent to ldlr knockout, whereas single deletion of Dab2 only slightly affects serum cholesterol. In the liver, Dab2 is expressed in sinusoid endothelial cells (not hepatocytes); in the absence of Arh, Dab2 in liver endothelial cells regulates HMG-CoA reductase levels in hepatocytes. ARH and Dab2 together account for the majority of LDLR adaptor function in cholesterol homeostasis. Double-knockout mouse model (arh−/−;dab2−/−), serum cholesterol measurement, HMG-CoA reductase Western blotting, cell-type-specific expression analysis Journal of lipid research High 27005486
2007 ARH protein is expressed in neurons throughout the mouse brain (cerebellum, brainstem, olfactory bulb, hippocampus, cortex). Yeast two-hybrid screening identified ARH interactions with LRP1, LRP8, amyloid precursor-like protein 1, and GABA receptor-associated protein-like 1; interactions with LRP1 and GABARAPL1 were confirmed by co-immunoprecipitation from transfected HEK293 cells. ARH mRNA is present in axons of primary sympathetic neurons. Yeast two-hybrid screen, co-immunoprecipitation from transfected HEK293 cells, RT-PCR and in situ hybridization for axonal mRNA Journal of neurochemistry Medium 17727637
2008 PCSK9-mediated LDLR degradation is partially independent of ARH function: the gain-of-function mutant PCSK9-D374Y reduced cell-surface LDLR by ~35% even in ARH-negative lymphocytes (compared to ~70% in normal lymphocytes), indicating an ARH-independent pathway for PCSK9 activity. FACS measurement of cell-surface LDLR in ARH-deficient vs. normal lymphocytes treated with conditioned medium containing PCSK9 variants Atherosclerosis Medium 19081568
2022 Deletion of LDLRAP1 in mice (Western diet) causes hypercholesterolemia and atherosclerotic plaque formation. Even on chow diet, LDLRAP1−/− mice are insulin-resistant. LDLRAP1 is highly expressed in visceral adipose tissue; LDLRAP1−/− adipocytes are larger, have reduced glucose uptake and reduced AKT phosphorylation, and increased CD36 expression, with hypoxic visceral adipose tissue showing dysregulated lipid storage gene signatures. LDLRAP1−/− mouse model, high-fat diet challenge, plaque burden quantification, insulin tolerance test, glucose uptake assay, AKT phosphorylation Western blot, CD36 expression, calorimetry, gene expression analysis of adipose tissue The American journal of pathology Medium 35460615
2025 ARH directly associates with the large-conductance Ca2+-activated K+ channel-α (BKα) via NPXY motifs in BKα's cytoplasmic domain (confirmed by co-immunoprecipitation). In ARH-KO mice, both ROMK and BKα protein levels are significantly higher in the renal cortex, and under potassium-deficient conditions ARH-KO mice show impaired downregulation of apical ROMK and BKα, establishing ARH-dependent endocytosis of both channels in the distal nephron. Sex-specific compensatory mechanisms (NCC upregulation in females; reduced ENaC cleavage and BK auxiliary subunits in males) maintain potassium balance in ARH-KO mice. Co-immunoprecipitation of ARH and BKα, immunoblotting of renal cortex from ARH-KO vs. WT mice, dietary potassium challenge, apical channel localization analysis American journal of physiology. Renal physiology High 41138214
2026 LDLRAP1 is identified as the primary cellular target of nitrodiphenyl-ether covalent inhibitors that block coronavirus HCoV-OC43 infection. Chemical proteomic profiling (AIBPP, competitive ABPP, LC-MS/MS) showed selective covalent modification at C119 of LDLRAP1, disrupting the LDLR–LDLRAP1 protein–protein interaction; loss of this interaction correlated with antiviral efficacy. Activity- and inactivity-based proteome profiling (AIBPP), competitive ABPP, LC-MS/MS, fluorescence polarization assay, covalent probe with alkyne tag Journal of medicinal chemistry Medium 41734033

Source papers

Stage 0 corpus · 64 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 Exogenous plant MIR168a specifically targets mammalian LDLRAP1: evidence of cross-kingdom regulation by microRNA. Cell research 829 21931358
1982 A human-hybridoma system based on a fast-growing mutant of the ARH-77 plasma cell leukemia-derived line. European journal of immunology 195 7140810
2002 ARH is a modular adaptor protein that interacts with the LDL receptor, clathrin, and AP-2. The Journal of biological chemistry 180 12221107
2006 The adaptor protein Dab2 sorts LDL receptors into coated pits independently of AP-2 and ARH. Journal of cell science 147 16984970
2002 The autosomal recessive hypercholesterolemia (ARH) protein interfaces directly with the clathrin-coat machinery. Proceedings of the National Academy of Sciences of the United States of America 143 12451172
2002 Autosomal recessive hypercholesterolaemia in Sardinia, Italy, and mutations in ARH: a clinical and molecular genetic analysis. Lancet (London, England) 107 11897284
2003 The adaptor protein ARH escorts megalin to and through endosomes. Molecular biology of the cell 84 14528014
2005 Autosomal recessive hypercholesterolemia (ARH) and homozygous familial hypercholesterolemia (FH): a phenotypic comparison. Atherosclerosis 77 16343504
2014 Structure and function of the ARH family of ADP-ribosyl-acceptor hydrolases. DNA repair 72 24746921
2005 The modular adaptor protein autosomal recessive hypercholesterolemia (ARH) promotes low density lipoprotein receptor clustering into clathrin-coated pits. The Journal of biological chemistry 70 16179341
2009 The ARH adaptor protein regulates endocytosis of the ROMK potassium secretory channel in mouse kidney. The Journal of clinical investigation 57 19841541
2004 The modular adaptor protein ARH is required for low density lipoprotein (LDL) binding and internalization but not for LDL receptor clustering in coated pits. The Journal of biological chemistry 57 15166224
2008 Degradation of LDLR protein mediated by 'gain of function' PCSK9 mutants in normal and ARH cells. Atherosclerosis 55 19081568
2014 The history of Autosomal Recessive Hypercholesterolemia (ARH). From clinical observations to gene identification. Gene 54 25225128
2002 Mutation in the ARH gene and a chromosome 13q locus influence cholesterol levels in a new form of digenic-recessive familial hypercholesterolemia. Circulation research 47 12016260
2010 AMN directs endocytosis of the intrinsic factor-vitamin B(12) receptor cubam by engaging ARH or Dab2. Traffic (Copenhagen, Denmark) 46 20088845
1999 Identification of neuronal input to the arcuate nucleus (ARH) activated during lactation: implications in the activation of neuropeptide Y neurons. Brain research 42 10196458
2022 Resveratrol Contrasts IL-6 Pro-Growth Effects and Promotes Autophagy-Mediated Cancer Cell Dormancy in 3D Ovarian Cancer: Role of miR-1305 and of Its Target ARH-I. Cancers 37 35565270
1990 Chromosome localization of human ARH genes, a ras-related gene family. Genomics 36 2407642
2008 The endocytic adaptor protein ARH associates with motor and centrosomal proteins and is involved in centrosome assembly and cytokinesis. Molecular biology of the cell 35 18417616
2014 The clathrin adaptor proteins ARH, Dab2, and numb play distinct roles in Niemann-Pick C1-Like 1 versus low density lipoprotein receptor-mediated cholesterol uptake. The Journal of biological chemistry 32 25331956
2017 Induction of MiR133a expression by IL-19 targets LDLRAP1 and reduces oxLDL uptake in VSMC. Journal of molecular and cellular cardiology 31 28257760
2005 Adaptor protein ARH is recruited to the plasma membrane by low density lipoprotein (LDL) binding and modulates endocytosis of the LDL/LDL receptor complex in hepatocytes. The Journal of biological chemistry 29 16129683
1984 ARH-77, an established human IgG-producing myeloma cell line. I. Morphology, B-cell phenotypic marker profile, and expression of Epstein-Barr virus. Cancer 27 6090003
2016 Endocytic adaptors Arh and Dab2 control homeostasis of circulatory cholesterol. Journal of lipid research 26 27005486
2011 ARH cooperates with AP-1B in the exocytosis of LDLR in polarized epithelial cells. The Journal of cell biology 26 21444685
2019 The ARH and Macrodomain Families of α-ADP-ribose-acceptor Hydrolases Catalyze α-NAD Hydrolysis. ACS chemical biology 25 31599159
2004 No genetic linkage or molecular evidence for involvement of the PCSK9, ARH or CYP7A1 genes in the Familial Hypercholesterolemia phenotype in a sample of Danish families without pathogenic mutations in the LDL receptor and apoB genes. Atherosclerosis 23 15530918
2004 A novel ARH splice site mutation in a Mexican kindred with autosomal recessive hypercholesterolemia. Human genetics 20 15599766
2014 Lycorine induces programmed necrosis in the multiple myeloma cell line ARH-77. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 19 25487618
2003 Autosomal recessive hypercholesterolemia in a Sicilian kindred harboring the 432insA mutation of the ARH gene. Atherosclerosis 18 12535754
2018 Novel combined variants of LDLR and LDLRAP1 genes causing severe familial hypercholesterolemia. Atherosclerosis 17 30270081
2016 Variable expressivity and co-occurrence of LDLR and LDLRAP1 mutations in familial hypercholesterolemia: failure of the dominant and recessive dichotomy. Molecular genetics & genomic medicine 15 27247956
2019 Common Variants of the Plant microRNA-168a Exhibit Differing Silencing Efficacy for Human Low-Density Lipoprotein Receptor Adaptor Protein 1 (LDLRAP1). MicroRNA (Shariqah, United Arab Emirates) 14 30501607
2013 S-nitrosylation of ARH is required for LDL uptake by the LDL receptor. Journal of lipid research 14 23564733
2009 ARH: predicting splice variants from genome-wide data with modified entropy. Bioinformatics (Oxford, England) 14 19889797
2007 Autosomal recessive hypercholesterolemia in Spanish kindred due to a large deletion in the ARH gene. Molecular genetics and metabolism 14 17686643
1984 ARH-77, an established human IgG-producing myeloma cell line. II. Growth kinetics, clonogenic capacity, chalone production, xenogeneic transplantations, and response to melphalan. Cancer 14 6236873
2020 Molecular insights into the coding region mutations of low-density lipoprotein receptor adaptor protein 1 (LDLRAP1) linked to familial hypercholesterolemia. The journal of gene medicine 13 32073192
2022 ARH Family of ADP-Ribose-Acceptor Hydrolases. Cells 12 36497109
2003 Clinical and biochemical characterisation of patients with autosomal recessive hypercholesterolemia (ARH). Nutrition, metabolism, and cardiovascular diseases : NMCD 12 14717060
2019 A new variant (c.1A>G) in LDLRAP1 causing autosomal recessive hypercholesterolemia: Characterization of the defect and response to PCSK9 inhibition. Atherosclerosis 10 30777337
2016 Cytotoxic Effects of Resveratrol, Rutin and Rosmarinic Acid on ARH-77 Human (Multiple Myeloma) Cell Line. Natural product communications 10 30549595
2014 Pharmacological treatment of a Sardinian patient affected by Autosomal Recessive Hypercholesterolemia (ARH). Journal of clinical lipidology 10 25670367
2007 Characterization of the adaptor protein ARH expression in the brain and ARH molecular interactions. Journal of neurochemistry 10 17727637
2020 Genetic associations between serum low LDL-cholesterol levels and variants in LDLR, APOB, PCSK9 and LDLRAP1 in African populations. PloS one 9 32084179
2013 Corchorus olitorius (jute) extract induced cytotoxicity and genotoxicity on human multiple myeloma cells (ARH-77). Pharmaceutical biology 8 23577798
2011 Premature senescence in cells from patients with autosomal recessive hypercholesterolemia (ARH): evidence for a role for ARH in mitosis. Arteriosclerosis, thrombosis, and vascular biology 8 21778424
2006 Autosomal recessive hypercholesterolaemia: discrimination of ARH protein and LDLR function in the homozygous FH phenotype. Clinica chimica acta; international journal of clinical chemistry 8 17150201
2022 Deletion of LDLRAP1 Induces Atherosclerotic Plaque Formation, Insulin Resistance, and Dysregulated Insulin Response in Adipose Tissue. The American journal of pathology 7 35460615
2021 RNA-sequencing of AVPV and ARH reveals vastly different temporal and transcriptomic responses to estradiol in the female rat hypothalamus. PloS one 7 34407144
2017 Analysis of the Genes Involved in Thiocyanate Oxidation during Growth in Continuous Culture of the Haloalkaliphilic Sulfur-Oxidizing Bacterium Thioalkalivibrio thiocyanoxidans ARh 2T Using Transcriptomics. mSystems 7 29285524
1983 Lymphokine factors inducing IgG production in human B-cell line ARH-77 and stimulatory effects of phorbol ester tumor promoter. Cellular immunology 7 6602661
2022 Autosomal Recessive Hypercholesterolemia Caused by a Novel LDLRAP1 Variant and Membranous Nephropathy in a Chinese Girl: A Case Report. Frontiers in cardiovascular medicine 6 35187127
2015 Complete genome sequence of Thioalkalivibrio paradoxus type strain ARh 1(T), an obligately chemolithoautotrophic haloalkaliphilic sulfur-oxidizing bacterium isolated from a Kenyan soda lake. Standards in genomic sciences 6 26594306
2014 ARH-seq: identification of differential splicing in RNA-seq data. Nucleic acids research 6 24920826
2015 Partial genome sequence of the haloalkaliphilic soda lake bacterium Thioalkalivibrio thiocyanoxidans ARh 2(T). Standards in genomic sciences 5 26512310
2003 Cloning and sequence analysis of tumor-associated gene hMMTAG2 from human multiple myeloma cell line ARH-77. Sheng wu hua xue yu sheng wu wu li xue bao Acta biochimica et biophysica Sinica 4 12545221
2004 ARH missense polymorphisms and plasma cholesterol levels. Clinical chemistry and laboratory medicine 3 15497461
2021 A Novel Splice Site Variant in the LDLRAP1 Gene Causes Familial Hypercholesterolemia. Iranian biomedical journal 2 34425670
2025 The endocytic adaptor ARH facilitates potassium conservation by regulating ROMK and BK. American journal of physiology. Renal physiology 1 41138214
2026 First LDLRAP1 and Recurrent LDLR Mutations in Tunisian Families With Familial Hypercholesterolemia. Journal of cellular and molecular medicine 0 41492187
2026 Nitro-Diphenyl Ethers as Emerging Cysteine-Targeting Covalent Warheads Enable Identification of Novel Target LDLRAP1 for Anticoronaviral Activity. Journal of medicinal chemistry 0 41734033
2024 Methylation status of LDLR, PCSK9 and LDLRAP1 is associated with cardiovascular events in familial hypercholesterolemia. Epigenomics 0 38884343

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