Affinage

LDLRAP1

Low density lipoprotein receptor adapter protein 1 · UniProt Q5SW96

Length
308 aa
Mass
33.9 kDa
Annotated
2026-04-28
67 papers in source corpus 20 papers cited in narrative 20 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LDLRAP1 (ARH) is a clathrin-associated sorting adaptor that couples FXNPXY-motif-containing receptors to the endocytic machinery, with a central role in hepatic LDL receptor internalization and systemic cholesterol homeostasis. Its PTB domain binds FXNPXY motifs in the cytoplasmic tails of LDLR, megalin, ROMK, BKα, and amnionless, while a clathrin-box (LLDLE) and a C-terminal AP-2-binding region bridge cargo to clathrin-coated pits; S-nitrosylation at C199 and C286 is required for the ARH–AP-2 interaction and efficient LDL uptake (PMID:12221107, PMID:23564733). Beyond endocytosis, ARH cooperates with AP-1B in basolateral LDLR exocytosis from recycling endosomes, associates with centrosomal and spindle components during mitosis, and regulates renal potassium channel trafficking; combined loss of ARH and Dab2 in mice recapitulates LDLR-knockout-level hypercholesterolemia, establishing these two adaptors as the principal mediators of hepatic LDLR function (PMID:21444685, PMID:18417616, PMID:19841541, PMID:27005486). Loss-of-function mutations in LDLRAP1 cause autosomal recessive hypercholesterolemia (PMID:15166224).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2002 High

    Establishing ARH as a tripartite endocytic adaptor resolved how LDLR internalization signals are decoded: the PTB domain reads the FXNPXY motif, a clathrin-box engages clathrin heavy chain with nanomolar affinity, and a C-terminal segment binds the AP-2 β2-adaptin appendage, together bridging cargo to the coat.

    Evidence Reconstituted in vitro pull-downs with recombinant domains, mutagenesis of NPVY and β2-adaptin residues, phosphoinositide binding assays, and colocalization in HeLa cells

    PMID:12221107 PMID:12451172

    Open questions at the time
    • Structural basis of PTB–FXNPXY recognition not resolved at atomic level in this study
    • Relative contribution of clathrin-box vs AP-2-binding region to in vivo function unclear
  2. 2004 High

    Analysis of ARH-null lymphocytes revealed that ARH not only internalizes LDLR but also stabilizes LDL binding to its receptor within coated pits, explaining why surface LDLR accumulation in ARH deficiency does not proportionally increase LDL capture.

    Evidence Electron microscopy quantification of LDLR in coated pits, LDL binding assays in ARH−/− vs normal lymphocytes

    PMID:15166224

    Open questions at the time
    • Mechanism by which ARH stabilizes LDL–LDLR association is not defined
    • Whether this reflects conformational effects on LDLR or simply pit retention is unresolved
  3. 2005 High

    Domain-deletion rescue in polarized hepatocytes and Arh−/− mice demonstrated that both the clathrin-box and the AP-2-binding region are individually necessary (alongside the PTB domain) for LDLR clustering and internalization, and that ARH is the dominant LDLR adaptor in hepatocytes (~80% of LDL uptake).

    Evidence Adenoviral rescue of ARH mutants in WIF-B polarized hepatocytes and Arh−/− mice; RNAi in HepG2 cells with quantitative LDL uptake

    PMID:16129683 PMID:16179341

    Open questions at the time
    • Why hepatocytes depend on ARH while fibroblasts rely on Dab2 is not mechanistically explained
  4. 2006 High

    Epistasis experiments placing ARH relative to Dab2 showed that Dab2 is the primary LDLR adaptor in non-hepatic cells (HeLa, fibroblasts), clustering LDLR independently of AP-2, while ARH functions as a secondary adaptor requiring AP-2 to operate—establishing cell-type-specific adaptor hierarchy.

    Evidence Double siRNA knockdown of Dab2 and ARH with EM quantification of LDLR coated-pit clustering in HeLa and fibroblasts

    PMID:16984970

    Open questions at the time
    • What determines differential expression/dominance of ARH vs Dab2 across tissues is unknown
    • Whether other adaptors compensate in double-depleted cells is unaddressed
  5. 2008 High

    Discovery of ARH at centrosomes and the mitotic apparatus, and defective centrosome assembly and prolonged cytokinesis in Arh−/− MEFs, revealed an unexpected non-endocytic function—implicating ARH in centrosome integrity and cell division.

    Evidence Co-IP with γ-tubulin and dynein, centrosome fractionation, confocal colocalization through mitotic stages, Arh−/− MEF and siRNA phenotyping

    PMID:18417616

    Open questions at the time
    • Direct molecular target of ARH at the centrosome is not identified
    • Whether centrosomal function involves the PTB domain or clathrin-binding is unknown
  6. 2009 High

    Identification of ROMK as a direct ARH cargo extended ARH function beyond lipoprotein metabolism: ARH binds a variant YxNPxFV signal in ROMK, mediates its clathrin-dependent endocytosis, and regulates renal potassium handling in vivo.

    Evidence Direct binding assay, co-IP, siRNA knockdown endocytosis assay in COS-7, Arh-KO mouse potassium challenge

    PMID:19841541

    Open questions at the time
    • Whether ARH regulation of ROMK is WNK1-dependent or parallel is not fully dissected
    • Structural basis for recognition of the variant YxNPxFV motif vs canonical FXNPXY is not resolved
  7. 2011 High

    ARH was shown to cooperate with the epithelial-specific adaptor AP-1B in basolateral exocytosis of LDLR from recycling endosomes, expanding ARH function from endocytic internalization to post-endocytic sorting/recycling.

    Evidence siRNA knockdown and point mutagenesis of ARH AP-1B interaction site in polarized epithelial cells, confocal colocalization, basolateral sorting assay

    PMID:21444685

    Open questions at the time
    • Whether ARH–AP-1B cooperation applies to non-LDLR cargo is untested
    • The molecular interface between ARH and AP-1B is not structurally resolved
  8. 2013 High

    S-nitrosylation at C199 and C286 was identified as a required post-translational modification for the ARH–AP-2 interaction and LDL uptake, establishing nitric oxide as a physiological regulator of ARH function distinct from Dab2.

    Evidence Site-directed mutagenesis of C199/C286, NOS inhibitor experiments, LDL uptake assays, AP-2 co-IP

    PMID:23564733

    Open questions at the time
    • Physiological signals that tune NO-dependent ARH activation in hepatocytes are not defined
    • Whether nitrosylation affects ARH functions beyond endocytosis (centrosome, recycling) is unknown
  9. 2016 High

    Double-knockout of Arh and Dab2 in mice produced hypercholesterolemia equivalent to LDLR knockout, proving that these two adaptors together account for essentially all LDLR-mediated cholesterol clearance; Dab2 in liver sinusoidal endothelial cells provides a compensatory pathway when ARH is absent.

    Evidence Arh/Dab2 double-KO mouse genetics, serum cholesterol, cell-type expression analysis, HMG-CoA reductase levels

    PMID:27005486

    Open questions at the time
    • How endothelial Dab2 communicates with hepatocyte cholesterol synthesis machinery is mechanistically unresolved
    • Whether additional minor adaptors exist in other tissues is not excluded
  10. 2022 Medium

    LDLRAP1-KO mice on a Western diet revealed adipose tissue phenotypes—enlarged adipocytes, impaired glucose uptake, reduced AKT phosphorylation, and insulin resistance—demonstrating a metabolic role for ARH beyond receptor endocytosis.

    Evidence LDLRAP1−/− mouse model, Western diet, calorimetry, glucose uptake assays, AKT phosphorylation immunoblot, CD36 expression

    PMID:35460615

    Open questions at the time
    • Molecular target of ARH in adipocyte insulin signaling is not identified
    • Whether adipose phenotype is cell-autonomous or secondary to hypercholesterolemia is not distinguished
    • Single-lab finding awaiting independent replication
  11. 2025 Medium

    Extension of ARH's renal cargo repertoire to BKα channels—which contain NPXY motifs and co-immunoprecipitate with ARH—showed that ARH regulates trafficking of multiple potassium channels in the distal nephron under dietary potassium restriction.

    Evidence Co-IP of ARH and BKα, ARH-KO mouse potassium-deficient diet challenge, immunoblot of kidney channel levels

    PMID:41138214

    Open questions at the time
    • Direct PTB-domain binding to BKα NPXY motif not demonstrated with purified proteins
    • Whether ARH deficiency causes clinical potassium handling defects in humans is unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • The mechanism by which ARH participates in centrosome assembly and mitotic progression, the identity of its direct centrosomal target, and the physiological significance of its adipose tissue metabolic function remain unresolved.
  • No centrosomal substrate or binding partner for the PTB domain has been identified
  • Cell-autonomous vs systemic origin of ARH-dependent adipose/metabolic phenotypes is undetermined
  • Structural basis of how nitrosylation at C199/C286 enables AP-2 binding is not resolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0038024 cargo receptor activity 4 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0031410 cytoplasmic vesicle 3 GO:0005768 endosome 2 GO:0005815 microtubule organizing center 2 GO:0005829 cytosol 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-5653656 Vesicle-mediated transport 8 R-HSA-1430728 Metabolism 2 R-HSA-1640170 Cell Cycle 2 R-HSA-382551 Transport of small molecules 2
Partners
AP1M2AP2B1CLTCKCNJ1KCNMA1LDLRLRP2TUBG1

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 ARH (LDLRAP1) functions as a modular adaptor protein: its N-terminal PTB domain binds the NPVY/FXNPXY internalization sequence in the LDLR cytoplasmic tail in a sequence-specific manner; a canonical clathrin-box (LLDLE) mediates high-affinity binding to clathrin heavy chain N-terminal domain (Kd ~44 nM); and a conserved C-terminal 20-aa region binds the beta2-adaptin appendage domain of AP-2. Pull-down assays with recombinant proteins, in vitro binding with purified bovine clathrin, mutagenesis of NPVY sequence and beta2-adaptin glutamate residue The Journal of biological chemistry High 12221107
2002 ARH binds directly to the FXNPXY motif of LDLR, to soluble clathrin trimers, to clathrin adaptors via the beta-subunit appendage domain, and to phosphoinositides; at steady state ARH colocalizes with endocytic proteins in HeLa cells and LDLR fluxes through peripheral ARH-positive sites before delivery to early endosomes. In vitro binding assays, subcellular colocalization by fluorescence microscopy, phosphoinositide-binding assay Proceedings of the National Academy of Sciences of the United States of America High 12451172
2005 ARH promotes LDLR clustering into clathrin-coated pits in polarized hepatocytes (WIF-B cells) and in vivo in Arh-/- mouse livers; the PTB domain plus either the clathrin-box or AP-2 binding region are both required for LDLR clustering and internalization; the FDNPVY sequence in the LDLR tail is required for ARH-dependent clustering. Mutagenesis of ARH domains, adenoviral rescue in WIF-B polarized hepatocytes and Arh-/- mice in vivo, fluorescence microscopy of LDLR distribution The Journal of biological chemistry High 16179341
2004 ARH is required not only for LDLR internalization but also for efficient LDL binding to the receptor on the cell surface; ARH-/- lymphocytes accumulate >20-fold more surface LDLR, predominantly outside coated pits, yet LDL binding is only ~2-fold increased, indicating ARH stabilizes LDL-LDLR association and receptor localization within the invaginating pit. Electron microscopy quantification of LDLR in coated pits, biochemical surface LDLR assays, LDL binding assays in ARH-/- vs. normal lymphocytes The Journal of biological chemistry High 15166224
2003 ARH binds to the first FXNPXY motif of the endocytic receptor megalin via its PTB domain, colocalizes with megalin in clathrin-coated pits and recycling endosomes, escorts megalin through early endosomes and tubular recycling endosomes, and expression of ARH enhances megalin-mediated uptake of 125I-lactoferrin. Yeast two-hybrid, GST pull-down, co-immunoprecipitation, confocal colocalization, functional uptake assay with radioiodinated ligand in MDCK cells expressing megalin mini-receptors Molecular biology of the cell High 14528014
2005 In HepG2 hepatocytes, ARH co-distributes with LDLR on the basolateral membrane; activation of LDLR-mediated endocytosis (but not LDL binding alone) promotes colocalization of ARH with the LDL-LDLR complex peaking at 2 min at 37°C; RNAi depletion of ARH (>70%) causes ~80% reduction in LDL internalization. Quantitative immunofluorescence microscopy, RNAi knockdown, LDL uptake assay in HepG2 polarized cells The Journal of biological chemistry High 16129683
2009 ARH directly binds the ROMK potassium channel via a variant endocytic signal (YxNPxFV) and recruits ROMK to clathrin-coated pits for constitutive and WNK1-stimulated endocytosis; ARH knockdown decreases basal ROMK endocytosis; ARH is predominantly expressed in the distal nephron, co-immunoprecipitates and colocalizes with ROMK in kidney; ARH protein abundance is modulated by dietary potassium inversely correlated with ROMK; ARH-knockout mice display altered ROMK response to potassium intake. Direct binding assay, co-immunoprecipitation, siRNA knockdown endocytosis assay in COS-7, immunolocalization in kidney, ARH-KO mouse phenotyping The Journal of clinical investigation High 19841541
2008 ARH associates with centrosomal proteins (gamma-tubulin, GPC2, GPC3) and motor proteins (dynein heavy and intermediate chains); ARH colocalizes with gamma-tubulin on isolated centrosomes; during mitosis ARH sequentially localizes to nuclear membrane, kinetochores, spindle poles, and midbody; Arh-/- MEFs show smaller/absent centrosomes, slower growth and prolonged cytokinesis; siRNA depletion of ARH in Rat-1 fibroblasts phenocopies this. Co-immunoprecipitation, centrosome fractionation, confocal colocalization, siRNA knockdown, analysis of Arh-/- MEFs, cell growth assays Molecular biology of the cell High 18417616
2011 ARH cooperates with the epithelial-specific clathrin adaptor AP-1B in basolateral exocytosis of LDLR from recycling endosomes; ARH colocalizes with AP-1B in recycling endosomes; knockdown of ARH causes apical missorting of truncated LDLR (LDLR-CT27 containing only the FxNPxY motif); an ARH mutation that disrupts its interaction with AP-1B specifically abrogates LDLR-CT27 exocytosis. siRNA knockdown of ARH in polarized epithelial cells, mutagenesis of ARH AP-1B interaction site, confocal colocalization, basolateral sorting assay The Journal of cell biology High 21444685
2011 ARH localizes to mitotic microtubules, nuclear envelope (with lamin B1), and spindle matrix (with clathrin heavy chain); ARH is phosphorylated in G2/M phase by a roscovitine-sensitive kinase (likely cdc2) at Ser14 identified by mass spectrometry; cells lacking ARH show disfigured nuclei and defective mitotic spindles and undergo premature senescence. Immunofluorescence localization, mass spectrometry phosphopeptide identification, kinase inhibitor (roscovitine) treatment, ARH RNAi in IMR90 cells, analysis of ARH patient cells Arteriosclerosis, thrombosis, and vascular biology Medium 21778424
2013 ARH requires nitric oxide for LDL uptake: nitric oxide S-nitrosylates ARH at C199 and C286, and these modifications are necessary for ARH association with the AP-2 component of clathrin-coated pits; without nitrosylation, ARH cannot target LDL-LDLR complexes to coated pits; NOS inhibition specifically impairs ARH-supported LDL uptake but not Dab2-supported LDL uptake. S-nitrosylation site mapping by mutagenesis (C199, C286), NOS inhibitor experiments, LDL uptake assays, AP-2 co-immunoprecipitation Journal of lipid research High 23564733
2010 ARH binds to FXNPXF signals in the cytoplasmic tail of amnionless (AMN), a component of the cubam receptor complex, thereby mediating endocytosis of cubam; the two AMN FXNPXF signals are functionally redundant and both can mediate cubam endocytosis through interaction with ARH (and Dab2). Yeast two-hybrid analysis, sequential mutagenesis of AMN FXNPXF motifs, expression of AMN mutants with endocytosis readout Traffic (Copenhagen, Denmark) Medium 20088845
2014 ARH and Dab2 do not bind NPC1L1 and are not required for NPC1L1 internalization; ARH specifically mediates LDLR-dependent LDL uptake but not NPC1L1-mediated cholesterol absorption, establishing that these PTB-domain adaptors have distinct cargo specificities despite structural similarity. Co-immunoprecipitation binding assays, siRNA knockdown of ARH/Dab2/Numb, cholesterol uptake and LDL uptake assays The Journal of biological chemistry Medium 25331956
2016 Genetic deletion of both Arh and Dab2 in mice causes profound hypercholesterolemia similar to ldlr homozygous knockout, whereas deletion of Dab2 alone has minimal effect; Dab2 is expressed in liver sinusoid endothelial cells (not hepatocytes) and in the absence of Arh, Dab2 in endothelial cells regulates cholesterol synthesis in hepatocytes, establishing that Arh and Dab2 together account for the majority of LDLR adaptor function in cholesterol homeostasis. Double-knockout mouse genetics (arh/dab2), serum cholesterol measurements, cell-type-specific expression analysis, HMG-CoA reductase level measurements Journal of lipid research High 27005486
2007 ARH mRNA and protein are expressed in neurons throughout the mouse brain (cerebellum, brainstem, hippocampus, cortex); yeast two-hybrid screening identified ARH interactions with amyloid precursor-like protein 1, LRP1, LRP8, and GABA receptor-associated protein-like 1; interactions with LRP1 and GABARAPL1 were verified by co-immunoprecipitation in transfected HEK293 cells; ARH mRNA is present in axons of sympathetic neurons. Yeast two-hybrid, co-immunoprecipitation in HEK293 cells, RT-PCR and in situ hybridization for axonal mRNA Journal of neurochemistry Medium 17727637
2022 LDLRAP1 deletion in mice (high-fat Western diet) leads to hypercholesterolemia, increased atherosclerotic plaque burden, increased weight gain, insulin resistance, and altered metabolic profile; LDLRAP1 is highly expressed in visceral adipose tissue; LDLRAP1-/- adipocytes are larger, have reduced glucose uptake and AKT phosphorylation, and increased CD36 expression, demonstrating a metabolic regulatory role in adipose tissue beyond LDLR endocytosis. LDLRAP1-/- mouse model, Western diet feeding, plaque quantification, calorimetry, glucose uptake assays, AKT phosphorylation by immunoblot, CD36 expression analysis The American journal of pathology Medium 35460615
2025 ARH directly associates with large-conductance Ca2+-activated K+ channel-alpha (BKα), which contains NPXY motifs, as confirmed by co-immunoprecipitation; ARH-KO mice show impaired downregulation of apical ROMK and BKα under potassium-deficient conditions, establishing ARH as a key regulator of both ROMK and BKα trafficking in the distal nephron. Co-immunoprecipitation of ARH and BKα, ARH-KO mouse model, immunoblotting of kidney ROMK and BKα protein levels, potassium dietary challenge experiments American journal of physiology. Renal physiology Medium 41138214
2026 Covalent modification of LDLRAP1 at C119 by nitrodiphenyl-ether covalent probes disrupts the LDLR-LDLRAP1 interaction; inhibition of this interaction correlates with antiviral efficacy against HCoV-OC43, identifying LDLRAP1 as a host antiviral target and C119 as a functionally important cysteine. Activity- and inactivity-based proteome profiling (AIBPP), competitive ABPP, LC-MS/MS, fluorescence polarization assay, antiviral efficacy assay Journal of medicinal chemistry Medium 41734033
2011 Exogenous plant MIR168a from rice binds to the human/mouse LDLRAP1 mRNA, inhibits LDLRAP1 expression in the liver, and consequently decreases LDL removal from mouse plasma. In vitro luciferase reporter assay for miRNA-mRNA interaction, in vivo feeding experiments in mice measuring liver LDLRAP1 protein and plasma LDL levels Cell research Medium 21931358
2006 In HeLa cells and fibroblasts, Dab2 (not ARH) is the primary adaptor for LDLR internalization and mediates LDLR clustering into coated pits independently of ARH and AP-2; when Dab2 is absent, ARH can mediate LDLR endocytosis but requires AP-2; ARH alone does not efficiently cluster LDLR into coated pits in these cell types, placing ARH as a secondary adaptor that accelerates later steps cooperatively with AP-2. siRNA knockdown of Dab2 and ARH, LDLR endocytosis assays, LDLR coated-pit clustering by electron microscopy, cell-type-specific analysis Journal of cell science High 16984970

Source papers

Stage 0 corpus · 67 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 823 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 146 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 142 12451172
2002 Autosomal recessive hypercholesterolaemia in Sardinia, Italy, and mutations in ARH: a clinical and molecular genetic analysis. Lancet (London, England) 106 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 76 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 69 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 53 25225128
2010 AMN directs endocytosis of the intrinsic factor-vitamin B(12) receptor cubam by engaging ARH or Dab2. Traffic (Copenhagen, Denmark) 46 20088845
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 46 12016260
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 36 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 34 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 28 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
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
2016 Endocytic adaptors Arh and Dab2 control homeostasis of circulatory cholesterol. Journal of lipid research 25 27005486
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
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
2013 S-nitrosylation of ARH is required for LDL uptake by the LDL receptor. Journal of lipid research 13 23564733
2003 Clinical and biochemical characterisation of patients with autosomal recessive hypercholesterolemia (ARH). Nutrition, metabolism, and cardiovascular diseases : NMCD 12 14717060
2022 ARH Family of ADP-Ribose-Acceptor Hydrolases. Cells 10 36497109
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
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
2014 Pharmacological treatment of a Sardinian patient affected by Autosomal Recessive Hypercholesterolemia (ARH). Journal of clinical lipidology 9 25670367
2013 Corchorus olitorius (jute) extract induced cytotoxicity and genotoxicity on human multiple myeloma cells (ARH-77). Pharmaceutical biology 8 23577798
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
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 7 21778424
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
2004 ARH missense polymorphisms and plasma cholesterol levels. Clinical chemistry and laboratory medicine 3 15497461
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 3 12545221
2021 A Novel Splice Site Variant in the LDLRAP1 Gene Causes Familial Hypercholesterolemia. Iranian biomedical journal 2 34425670
2025 Inhibition of ARH2 by pH/ROS-responsive nanosystem for improved lung adenocarcinoma immunochemotherapy. Bioactive materials 1 40801020
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 Low-Temperature Ru-Ru Hybrid Bonding: Ar/H2 Plasma and NH4OH Synergistic Activation for Ultrahigh Density Interconnection. ACS applied materials & interfaces 0 41641610
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
2023 ADP-ribose-acceptor hydrolase 2 ( Arh2 ) deficiency results in cardiac dysfunction, tumorigenesis, inflammation, and decreased survival. bioRxiv : the preprint server for biology 0 36798189