Affinage

ANK1

Ankyrin-1 · UniProt P16157

Length
1881 aa
Mass
206.3 kDa
Annotated
2026-04-28
100 papers in source corpus 25 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ANK1 encompasses two distinct gene products with non-overlapping functions: erythroid ankyrin-1, a scaffold protein whose 24-ANK-repeat membrane-binding domain provides two cooperatively coupled binding sites (repeats 7–12 and 13–24) for the anion exchanger AE1/band 3 and links membrane proteins to the spectrin-actin cytoskeleton (PMID:7665627, PMID:7798219, PMID:12456646); and the ANKH/progressive ankylosis protein, a multipass transmembrane transporter that exports inorganic pyrophosphate and ATP across the plasma membrane to regulate extracellular PPi levels, tissue mineralization, and skeletal homeostasis (PMID:10894769, PMID:17186460, PMID:20604715). Loss-of-function mutations in erythroid ankyrin-1 disrupt binding to β-spectrin and AE1 and prevent plasma membrane localization, causing hereditary spherocytosis, while dominant ANKH mutations abolish PPi transport and cause craniometaphyseal dysplasia (PMID:31016877, PMID:11326338). Beyond skeletal tissues, ANKH functions as a citrate transporter in vascular smooth muscle cells, where its loss causes cytosolic citrate accumulation, acetyl-CoA–driven histone hyperacetylation (H3K23/H3K27/H4K5), and inflammatory gene activation promoting aortic aneurysm (PMID:39513269).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1994 High

    Mapping the minimal AE1 determinants for ankyrin-1 binding established that the N-terminal 79 residues of erythroid AE1 are required for high-affinity interaction, explaining why the kidney AE1 isoform is ankyrin-independent.

    Evidence Cell-free binding assay with radiolabeled ANK1 fragment and full-length vs. truncated AE1 constructs

    PMID:7798219

    Open questions at the time
    • Structural basis of the AE1–ankyrin interface at atomic resolution was not resolved
    • Whether post-translational modifications regulate binding affinity was not tested
  2. 1995 High

    Demonstrating two cooperatively coupled AE1-binding sites within the 24-ANK-repeat domain (repeats 7–12 and 13–24) established the modular, multivalent architecture of ankyrin-1's membrane-binding domain.

    Evidence In vitro binding assays with recombinant ANK repeat subdomains; Hill coefficient analysis

    PMID:7665627

    Open questions at the time
    • How cooperativity is mechanistically transmitted between the two sites was unknown
    • Whether additional membrane proteins engage other repeat subdomains was not addressed
  3. 2000 High

    Positional cloning of the progressive ankylosis locus identified ANK as a multipass transmembrane protein controlling extracellular pyrophosphate levels, establishing a new gene product (distinct from erythroid ankyrin-1) as a PPi transporter and mineralization regulator.

    Evidence Positional cloning; PPi measurement in cultured cells from ank/ank mutant mice

    PMID:10894769

    Open questions at the time
    • Whether ANK transports PPi directly or facilitates its release indirectly was not resolved
    • Topology and oligomeric state of the transporter were unknown
  4. 2001 High

    Identification of dominant ANK mutations in craniometaphyseal dysplasia families linked ANKH loss-of-function to a human skeletal disease, complementing the mouse ank/ank phenotype.

    Evidence Mutational analysis in CMD families; identification of in-frame deletions and insertions in a cytosolic domain

    PMID:11326338

    Open questions at the time
    • Biochemical proof that CMD mutations abrogate transport was not yet available
    • Genotype-phenotype spectrum (CMD vs. chondrocalcinosis) was not explained mechanistically
  5. 2002 High

    The crystal structure of ANK repeats 13–24 revealed a contiguous spiral stack with a large central cavity, providing the first structural framework for understanding how ankyrin-1 engages ion transporters and other membrane proteins.

    Evidence X-ray crystallography of ANK repeat 13–24 construct

    PMID:12456646

    Open questions at the time
    • Full-length ankyrin-1 structure was not obtained
    • Co-crystal with AE1 was not reported
  6. 2003 High

    Functional interdependence between ANK and NPP1/PC-1 was established: ANK requires PC-1 enzymatic activity to elevate extracellular PPi, and both contribute to osteopontin expression and mineralization control in osteoblasts.

    Evidence Culture of PC-1−/− and ank/ank calvarial osteoblasts; transfection rescue with PC-1; PPi and OPN measurement

    PMID:12817751

    Open questions at the time
    • Whether ANK and PC-1 physically interact was not tested
    • Relative contributions of ANK vs. PC-1 to PPi levels in non-osteoblast tissues were unknown
  7. 2004 High

    Triple genetic epistasis among TNAP, NPP1, and ANK demonstrated that these three genes form a coordinated regulatory circuit controlling extracellular PPi and mineralization in vivo.

    Evidence Crossbreeding Akp2−/−, ank/ank, and Enpp1−/− mice; PPi measurement; OPN assays

    PMID:15039209

    Open questions at the time
    • Quantitative modeling of PPi flux through each pathway was lacking
    • Whether additional PPi transporters compensate was not addressed
  8. 2005 High

    In growth plate chondrocytes, ANK-exported PPi is hydrolyzed by alkaline phosphatase to Pi, which feeds back to upregulate ALP expression, establishing ANK as a rate-limiting step in a mineralization-promoting loop.

    Evidence ANK siRNA and overexpression in chondrocytes; PPi/Pi measurements; ALP activity assays

    PMID:15601852

    Open questions at the time
    • Whether this PPi→Pi→ALP loop operates in non-cartilage tissues was untested
    • Kinetic parameters of ANK transport in chondrocytes were not determined
  9. 2006 High

    Reconstitution of saturable PPi transport in Xenopus oocytes proved ANK is a bona fide transporter rather than an indirect regulator, and disease-specific mutations (CMD vs. chondrocalcinosis) were functionally segregated by their transport capacity.

    Evidence Radiolabeled PPi transport in Xenopus oocytes; BAC transgenic mouse rescue of ank/ank

    PMID:17186460

    Open questions at the time
    • Ion coupling mechanism (symport/antiport) was not determined
    • Transporter structure remained unknown
  10. 2009 Medium

    Discovery that HIF-1α binds ANK promoter HRE-1 and represses ANK expression in hypoxia connected oxygen sensing to PPi metabolism in cartilage.

    Evidence ChIP for HIF-1α at ANK HREs; luciferase reporter assays with HRE mutagenesis; oxygen tension manipulation in chondrocytes

    PMID:19419319

    Open questions at the time
    • In vivo relevance of HIF-mediated ANK repression was not confirmed with conditional HIF knockout in cartilage
    • Whether HIF regulation of ANK occurs outside cartilage was unknown
  11. 2010 Medium

    Multiple studies in 2010 expanded ANK's biological roles: joint-specific conditional knockout proved cell-autonomous anti-mineralization function; ANK was shown to transport extracellular ATP in addition to PPi; ANK maintained chondrocyte differentiation through PPi-dependent suppression of Wnt-5a/β-catenin signaling; and the CMD knockin model revealed cell-autonomous osteoclast defects including impaired actin ring formation.

    Evidence Gdf5-Cre conditional KO (PMID:16869722); bioluminescent ATP assay with ANK overexpression/knockdown (PMID:20604715); siRNA with Tcf/Lef reporter and PPi rescue (PMID:20133941); Ank KI/KI osteoclast culture and bone marrow transplant (PMID:21149338); ANK localization in renal cells (PMID:17762177)

    PMID:16869722 PMID:17762177 PMID:20133941 PMID:20200976 PMID:20604715 PMID:21149338

    Open questions at the time
    • Selectivity of ANK for PPi vs. ATP vs. other anions was not determined with purified protein
    • Whether Wnt-5a regulation is direct or secondary to PPi-mediated signaling was unclear
    • Structural basis for multi-substrate transport was unknown
  12. 2010 Medium

    ANK was found at the trans-Golgi network, clathrin-coated vesicles, and plasma membrane, and its loss impaired tubular carrier formation and transferrin endocytosis, revealing an unexpected role in intracellular membrane trafficking.

    Evidence Immunofluorescence; co-immunoprecipitation with clathrin/AP complexes; RNAi with transferrin endocytosis assays

    PMID:27466194

    Open questions at the time
    • Relationship between trafficking function and PPi transport was not established
    • Whether trafficking defects contribute to disease phenotypes was untested
    • Single-lab finding not yet independently replicated
  13. 2014 Medium

    Identification of MYBBP1a and SPHK1 as ANK-interacting proteins linked ANK to NF-κB-dependent catabolic signaling in chondrocytes, showing that ANK scaffolds signaling complexes beyond its transporter role.

    Evidence Yeast two-hybrid confirmed by co-IP; domain-specific ANK mutants; NF-κB luciferase reporter; explant proteoglycan loss assay

    PMID:24747173

    Open questions at the time
    • Whether MYBBP1a interaction is relevant in vivo was not tested
    • Stoichiometry and regulation of the ANK–MYBBP1a complex were not determined
  14. 2019 Medium

    Loss-of-function ANK1 mutations were shown to disrupt plasma membrane localization and interactions with β-spectrin and AE1, directly linking erythroid ankyrin-1 dysfunction to hereditary spherocytosis pathogenesis.

    Evidence Co-immunoprecipitation with SPTB and SLC4A1; subcellular localization of WT and mutant ANK1; osmotic fragility assay

    PMID:31016877

    Open questions at the time
    • Structural consequences of specific mutations on the ANK repeat architecture were not resolved
    • Whether any mutations retain partial function was not quantified
  15. 2024 High

    Identification of ANK as a citrate transporter in VSMCs expanded its substrate repertoire and revealed an epigenetic mechanism — citrate accumulation → acetyl-CoA → histone hyperacetylation → inflammatory gene activation — linking ANK to aortic aneurysm.

    Evidence VSMC-specific Ank KO mice; untargeted metabolomics; CUT&Tag for histone acetylation; ANK overexpression and acetyl-CoA inhibitor rescue in aneurysm models

    PMID:39513269

    Open questions at the time
    • Whether citrate transport is direct or mediated via PPi-dependent metabolic remodeling was not fully distinguished
    • Relative importance of citrate vs. PPi transport in vascular biology is unclear
    • ANK transporter structure still not determined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Critical open questions include: the atomic structure and transport mechanism of the ANKH multipass transmembrane protein; the substrate selectivity profile (PPi, ATP, citrate, and potentially other anions); whether the trafficking and scaffolding functions of ANKH are mechanistically linked to its transport activity; and the full-length structure of erythroid ankyrin-1 in complex with AE1 and spectrin.
  • No high-resolution structure of ANKH transporter exists
  • Ion coupling mechanism and energetics of transport are undetermined
  • Full-length ankyrin-1–AE1–spectrin ternary complex structure is lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 5 GO:0005198 structural molecule activity 3 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005886 plasma membrane 4 GO:0005794 Golgi apparatus 2 GO:0005856 cytoskeleton 2 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-382551 Transport of small molecules 5 R-HSA-1430728 Metabolism 4 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3
Partners
CLTCENPP1MYBBP1ASLC4A1SPHK1SPTB
Complex memberships
ankyrin-1/spectrin/AE1 membrane skeleton complex

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 The mouse Ank gene encodes a multipass transmembrane protein (ANK) that controls extracellular pyrophosphate levels in cultured cells, acting as a pyrophosphate transport/channel protein that regulates tissue calcification and arthritis. Positional cloning of the progressive ankylosis locus; functional assay of pyrophosphate levels in cultured cells from ank/ank mutant mice Science High 10894769
2001 Dominant mutations in the ANK transmembrane protein cause craniometaphyseal dysplasia; the mutations cluster in a cytosolic domain and are proposed to act as dominant negatives on pyrophosphate transport function. Mutational analysis of positional candidate genes in CMD families; identification of in-frame deletions and insertion mutations American Journal of Human Genetics High 11326338
2002 Crystal structure of ANK repeats 13–24 of human ankyrin-R reveals a contiguous spiral stack; the spectrin-binding domain associates as an extended strand; models indicate ion transporters such as the anion exchanger bind in a large central cavity while clathrin and cell adhesion molecules bind outside the cavity. X-ray crystallography of ANK repeat 13–24 construct; structural modeling of binding interactions The EMBO Journal High 12456646
1995 The 24 ANK repeats of erythrocyte ankyrin (ANK1) membrane-binding domain form four subdomains; two distinct but cooperatively coupled binding sites for the anion exchanger (Cl⁻/HCO₃⁻ exchanger) are present — one using repeats 7–12 and the other requiring repeats 13–24. In vitro binding assays using recombinant ANK repeat subdomains; Hill coefficient analysis of cooperativity Journal of Biological Chemistry High 7665627
1994 The NH₂-terminal 79 amino acids of erythroid AE1 (band 3) are essential for high-affinity binding to ANK1; the kidney AE1 isoform (kAE1), which lacks these 79 residues, does not bind ANK1 in vitro. Cell-free binding assay with ¹²⁵I-labeled ANK1 fragment R13-H; transfection of full-length and truncated AE1 constructs; Kd determination Journal of Biological Chemistry High 7798219
2006 Wild-type ANK mediates saturable transport of pyrophosphate ions across the plasma membrane (half-maximal at physiological PPi levels) in Xenopus oocytes; craniometaphyseal dysplasia mutations abolish transport activity and cannot rescue Ank null mice, while chondrocalcinosis mutations retain transport activity and rescue the joint-fusion phenotype. Radiolabeled pyrophosphate transport assay in Xenopus oocytes; transgenic mouse rescue experiments with bacterial artificial chromosome constructs carrying human mutations; micro-CT American Journal of Human Genetics High 17186460
2004 ANK and NPP1 (PC-1) coordinately regulate extracellular PPi and osteopontin levels; ANK-deficient (ank/ank) and NPP1-deficient mice have decreased extracellular PPi and are hypermineralized; double-mutant (Akp2⁻/⁻; ank/ank) mice show partial normalization of PPi and OPN, demonstrating genetic epistasis among TNAP, NPP1, and ANK in mineralization control. Genetic epistasis via crossbreeding Akp2⁻/⁻, ank/ank, and Enpp1⁻/⁻ mice; PPi measurement; OPN mRNA and serum assays; osteoblast culture with exogenous PPi American Journal of Pathology High 15039209
2005 ANK transports intracellular PPi to the extracellular milieu in growth plate chondrocytes; increased ANK activity elevates extracellular PPi, which is hydrolyzed to Pi by alkaline phosphatase, triggering Pi-mediated upregulation of alkaline phosphatase expression and subsequent mineralization; blocking ANK transport increases intra- and extracellular PPi and inhibits mineralization. Ank siRNA knockdown and overexpression in growth plate chondrocytes; PPi concentration measurements; alkaline phosphatase activity assays; phosphate transport inhibitor (PFA) studies; gene expression analysis Molecular and Cellular Biology High 15601852
2003 ANK deficiency (ank/ank) and PC-1 deficiency both cause decreased extracellular PPi and osteopontin expression in osteoblasts, leading to hypercalcification; soluble PC-1 corrected both extracellular PPi and OPN deficiencies; ANK requires PC-1 to elevate extracellular PPi, indicating functional interdependence. Culture of PC-1⁻/⁻ and ank/ank calvarial osteoblasts; NPP activity assay; transfection rescue with PC-1 or NPP3; OPN measurement; calcification assays Journal of Bone and Mineral Research High 12817751
2007 TGF-β1 increases ANK expression via Ras/Raf-1/ERK and Ca²⁺-dependent PKC pathways (but not p38-MAPK, PKA, or Smad7 pathway), and ANK contributes ~60% of TGF-β1-induced extracellular PPi generation in chondrocytes. siRNA knockdown of ANK and PC-1; selective kinase inhibitors; dominant-negative/overexpression plasmid strategy; quantitative PCR and Western blot; PPi quantification Arthritis Research & Therapy Medium 18034874
2010 ANK localizes to the trans-Golgi network, clathrin-coated vesicles, and plasma membrane; ANK functionally interacts with clathrin and AP complexes; loss of ANK reduces tubular membrane carrier formation from the TGN, causes perinuclear accumulation of early endosomes, and impairs transferrin endocytosis. Immunofluorescence localization; co-immunoprecipitation with clathrin/AP complexes; RNAi knockdown with quantitative membrane trafficking assays (transferrin endocytosis, tubule formation) Human Molecular Genetics Medium 27466194
2010 ANK is required locally in joints to inhibit postnatal mineral formation; joint-specific deletion of ANK (using Gdf5-Cre) produces joint mineralization and ankylosis, demonstrating that ANK function is cell-autonomous within joint tissue. Conditional knockout via Gdf5-Cre/loxP; null allele generation by homologous recombination; joint range-of-motion assays; micro-CT; histology Journal of Bone and Mineral Research High 16869722
2010 ANK deficiency suppresses osteoblastic differentiation and osteoclastogenesis in ank/ank bone marrow cells; ANK overexpression increases Runx2 transcriptional activity and osterix expression; exogenous extracellular PPi or Pi partially rescues delayed osteoblastogenesis. Bone marrow stromal cell culture from ank/ank mice; siRNA and overexpression in MC3T3-E1; alkaline phosphatase activity; gene expression; luciferase reporter for Runx2 transcriptional activity; osteoclast differentiation assays Journal of Bone and Mineral Research Medium 20200976
2010 ANK overexpression in chondrocytes increases extracellular ATP levels 10-fold; ANK siRNA suppresses both basal and hypotonic-stress-induced ATP efflux; this effect is mimicked by the ANK inhibitor probenecid, implicating ANK as a transporter of extracellular ATP as well as PPi. Adenoviral overexpression and siRNA knockdown of ANK in chondrocytes; bioluminescent ATP assay; pharmacological inhibitors of ATP egress pathways; hypotonic stress model Connective Tissue Research / Arthritis Research & Therapy Medium 20604715 24286344
2010 ANK maintains the differentiated chondrocyte phenotype by controlling canonical Wnt signaling in a Wnt-5a-dependent manner; ANK knockdown activates Wnt-5a and β-catenin nuclear translocation; PPi supplementation compensates for ANK deficiency on Type II collagen, Sox-9, and Wnt-5a expression. siRNA knockdown of ANK; Tcf/Lef reporter assay; β-catenin nuclear translocation by immunoblot; type II collagen and Sox-9 mRNA; conditioned medium transfer experiments Journal of Biological Chemistry Medium 20133941
2014 ANK interacts with MYBBP1a via its C-terminal cytoplasmic loop and with SPHK1 via its N-terminal region; these interactions modulate NF-κB activity and catabolic events in IL-1β-treated chondrocytes — loss of ANK/MYBBP1a interaction increases nuclear MYBBP1a, decreases NF-κB activity, and reduces MMP-13 expression. Yeast two-hybrid screening; co-immunoprecipitation; domain-specific ANK mutants; NF-κB luciferase reporter; immunohistochemistry; femoral head explant proteoglycan loss assay Osteoarthritis and Cartilage Medium 24747173
2010 ANK localizes to the lateral and apical plasma membranes of renal collecting duct epithelial cells; a loss-of-function mutation (Glu440X) causes Golgi retention of ANK-GFP rather than normal plasma membrane trafficking, indicating that proper trafficking is required for transport function. Immunohistochemistry and GFP fusion protein transfection in mIMCD3 cells; co-localization with organelle markers; comparison of wild-type vs. mutant ANK-GFP subcellular distribution Cellular Physiology and Biochemistry Medium 17762177
2024 ANK acts as a citrate membrane transporter in vascular smooth muscle cells (VSMCs); ANK deficiency causes cytosolic citrate accumulation, increased acetyl-CoA production, histone acetylation at H3K23/H3K27/H4K5, and transcriptional activation of inflammatory genes, promoting aortic aneurysm formation. VSMC-specific Ank knockout mice in Ang II- and CaPO4-induced AA models; untargeted metabolomics; CUT&Tag analysis of histone acetylation; ANK overexpression; acetyl-CoA inhibitor rescue experiments Circulation Research High 39513269
2010 HIF-1α and HIF-2α are negative regulators of ANK expression in nucleus pulposus cells; HIF binds to hypoxia-responsive elements (HREs) in the ANK promoter; silencing HIF-1α or HIF-2α increases ANK expression; HIF-1 requires only one HRE whereas HIF-2 requires both HREs to suppress ANK promoter activity. siRNA knockdown of HIF-1α/2α; luciferase reporter assays with wild-type and HRE-mutagenized ANK promoter; HIF-1β-null embryonic fibroblasts; ChIP not explicitly stated but promoter occupancy inferred from reporter mutagenesis Arthritis and Rheumatism Medium 20496369
2009 HIF-1α binds to HRE-1 (but not HRE-2) of the ANK proximal promoter in normoxia more avidly than in hypoxia, suppressing ANK expression; ANK expression and extracellular PPi levels are repressed in hypoxic conditions in growth plate chondrocytes in a HIF-1-dependent manner. Chromatin immunoprecipitation (ChIP) for HIF-1α at ANK HREs; HIF-1α knockdown; luciferase reporter assays with mutagenized HREs; oxygen tension manipulation Journal of Bone and Mineral Research Medium 19419319
2003 ANK protein is expressed in neurons (predominantly in thalamus, cortical layers III and V, Purkinje cells, anterior horn neurons) and on both cell bodies and dendrites in primary neuronal cultures; ANK immunoreactivity increases in rat amygdala, hippocampus CA2/CA3, and cerebral cortex after seizure induction. Immunohistochemistry of human and rat brain; primary mouse neuronal cell culture immunostaining; kainate-induced seizure model with immunohistochemistry Laboratory Investigation Medium 12861042
2019 ANK1 methylation at its promoter CpG island is associated with co-regulation of the intragenic microRNA miR-486-5p; siRNA-mediated ANK1 knockdown reduces miR-486-5p expression, and DNA methylation inhibitor 5-aza-2'-deoxycytidine induces both ANK1 and miR-486-5p, demonstrating that ANK1 methylation regulates miR-486-5p expression in lung cancer. siRNA knockdown; 5-aza-2'-deoxycytidine treatment; quantitative methylation analysis; expression correlation in TCGA dataset Cancer Letters Medium 28965852
2010 ANK Phe377del mutation (CMD model) causes cell-autonomous impairment of osteoblast mineralization and osteoclastogenesis; Ank(KI/KI) osteoclasts show disrupted actin ring formation and impaired cell fusion; increased bone mass is partially rescued by bone marrow transplant, supporting reduced osteoclastogenesis as a contributor to hyperostosis. Knockin mouse model; osteoblast and macrophage cultures; ENPP1 activity assay; gene expression; bone marrow transplantation rescue Human Molecular Genetics Medium 21149338
2019 Loss-of-function ANK1 mutations prevent the protein from localizing to the plasma membrane and disrupt its interactions with SPTB (β-spectrin) and SLC4A1 (band 3/AE1), causing hereditary spherocytosis. In vitro expression of wild-type and mutant ANK1 constructs; co-immunoprecipitation with SPTB and SLC4A1; subcellular localization by immunofluorescence; osmotic fragility assay Journal of Cellular and Molecular Medicine Medium 31016877

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 Alzheimer's disease: early alterations in brain DNA methylation at ANK1, BIN1, RHBDF2 and other loci. Nature neuroscience 736 25129075
2000 Role of the mouse ank gene in control of tissue calcification and arthritis. Science (New York, N.Y.) 515 10894769
2014 Methylomic profiling implicates cortical deregulation of ANK1 in Alzheimer's disease. Nature neuroscience 439 25129077
2004 Concerted regulation of inorganic pyrophosphate and osteopontin by akp2, enpp1, and ank: an integrated model of the pathogenesis of mineralization disorders. The American journal of pathology 400 15039209
1992 The ANK repeat: a ubiquitous motif involved in macromolecular recognition. Trends in cell biology 172 14731966
2002 Crystal structure of a 12 ANK repeat stack from human ankyrinR. The EMBO journal 166 12456646
1999 Integrin-linked kinase is localized to cell-matrix focal adhesions but not cell-cell adhesion sites and the focal adhesion localization of integrin-linked kinase is regulated by the PINCH-binding ANK repeats. Journal of cell science 163 10574708
2003 Linked deficiencies in extracellular PP(i) and osteopontin mediate pathologic calcification associated with defective PC-1 and ANK expression. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 158 12817751
2001 Autosomal dominant craniometaphyseal dysplasia is caused by mutations in the transmembrane protein ANK. American journal of human genetics 143 11326338
1995 The ANK repeats of erythrocyte ankyrin form two distinct but cooperative binding sites for the erythrocyte anion exchanger. The Journal of biological chemistry 103 7665627
2006 Biochemical and genetic analysis of ANK in arthritis and bone disease. American journal of human genetics 94 17186460
2016 Mutational characteristics of ANK1 and SPTB genes in hereditary spherocytosis. Clinical genetics 76 26830532
2006 Control of axonal sprouting and dendrite branching by the Nrg-Ank complex at the neuron-glia interface. Current biology : CB 76 16920632
2010 Anaplasma phagocytophilum and Ehrlichia chaffeensis type IV secretion and Ank proteins. Current opinion in microbiology 72 20053580
2002 Up-regulated expression of cartilage intermediate-layer protein and ANK in articular hyaline cartilage from patients with calcium pyrophosphate dihydrate crystal deposition disease. Arthritis and rheumatism 70 12483726
1984 Hereditary joint disorder in progressive ankylosis (ank/ank) mice. I. Association of calcium hydroxyapatite deposition with inflammatory arthropathy. Arthritis and rheumatism 70 6095872
2012 Polydnavirus Ank proteins bind NF-κB homodimers and inhibit processing of Relish. PLoS pathogens 68 22654665
2005 Role of the progressive ankylosis gene (ank) in cartilage mineralization. Molecular and cellular biology 68 15601852
1996 Roles of the RAM and ANK domains in signaling by the C. elegans GLP-1 receptor. The EMBO journal 68 9003776
2000 Comparison of the nucleotide sequences of 16S rRNA, 444 Ep-ank, and groESL heat shock operon genes in naturally occurring Ehrlichia equi and human granulocytic ehrlichiosis agent isolates from Northern California. Journal of clinical microbiology 62 10747108
2018 A cross-brain regions study of ANK1 DNA methylation in different neurodegenerative diseases. Neurobiology of aging 58 30439595
2010 ANK, a host cytoplasmic receptor for the Tobacco mosaic virus cell-to-cell movement protein, facilitates intercellular transport through plasmodesmata. PLoS pathogens 58 21124937
2006 Mineral formation in joints caused by complete or joint-specific loss of ANK function. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 58 16869722
2004 Upregulated ank expression in osteoarthritis can promote both chondrocyte MMP-13 expression and calcification via chondrocyte extracellular PPi excess. Osteoarthritis and cartilage 57 15023384
2000 Sequence analysis of the ank gene of granulocytic ehrlichiae. Journal of clinical microbiology 56 10921951
2010 Progressive ankylosis protein (ANK) in osteoblasts and osteoclasts controls bone formation and bone remodeling. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 54 20200976
2013 Type 2 diabetes risk alleles near BCAR1 and in ANK1 associate with decreased β-cell function whereas risk alleles near ANKRD55 and GRB14 associate with decreased insulin sensitivity in the Danish Inter99 cohort. The Journal of clinical endocrinology and metabolism 51 23457408
2018 Orientia tsutsugamushi uses two Ank effectors to modulate NF-κB p65 nuclear transport and inhibit NF-κB transcriptional activation. PLoS pathogens 49 29734393
2010 Parallel regulation of extracellular ATP and inorganic pyrophosphate: roles of growth factors, transduction modulators, and ANK. Connective tissue research 46 20604715
1994 The major kidney AE1 isoform does not bind ankyrin (Ank1) in vitro. An essential role for the 79 NH2-terminal amino acid residues of band 3. The Journal of biological chemistry 46 7798219
2010 A Phe377del mutation in ANK leads to impaired osteoblastogenesis and osteoclastogenesis in a mouse model for craniometaphyseal dysplasia (CMD). Human molecular genetics 41 21149338
2002 The alpha-helical D1 domain of the tobacco bZIP transcription factor BZI-1 interacts with the ankyrin-repeat protein ANK1 and is important for BZI-1 function, both in auxin signaling and pathogen response. The Journal of biological chemistry 39 12499372
2007 Inorganic pyrophosphate generation by transforming growth factor-beta-1 is mainly dependent on ANK induction by Ras/Raf-1/extracellular signal-regulated kinase pathways in chondrocytes. Arthritis research & therapy 38 18034874
2019 Ankyrin repeat-containing N-Ank proteins shape cellular membranes. Nature cell biology 37 31548610
2009 Introduction of a Phe377del mutation in ANK creates a mouse model for craniometaphyseal dysplasia. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 37 19257826
2002 Developmental and TGF-beta-mediated regulation of Ank mRNA expression in cartilage and bone. Osteoarthritis and cartilage 37 12056852
1991 Dinucleotide repeat polymorphism at the human ankyrin gene (ANK1). Nucleic acids research 36 1826765
1975 Human karyotype polymorphism. III. Routine ank fluorescence microscopic investigation of chromosomes in normal adults and mentally retarded children. Humangenetik 36 125221
2013 The progressive ankylosis gene product ANK regulates extracellular ATP levels in primary articular chondrocytes. Arthritis research & therapy 35 24286344
2000 The ank gene story. Arthritis research 35 11178113
2017 ANK1 is up-regulated in laser captured microglia in Alzheimer's brain; the importance of addressing cellular heterogeneity. PloS one 34 28700589
2017 ANK1 Methylation regulates expression of MicroRNA-486-5p and discriminates lung tumors by histology and smoking status. Cancer letters 34 28965852
2016 The Role of ANK in Calcium Pyrophosphate Deposition Disease. Current rheumatology reports 29 27032788
1989 Progressive ankylosis (ank/ank) in mice: an animal model of spondyloarthropathy. II. Light and electron microscopic findings. The Journal of rheumatology 29 2541245
2011 Effects of mechanical strain on ANK, ENPP1 and TGF-β1 expression in rat endplate chondrocytes in vitro. Molecular medicine reports 28 21674130
2008 Bacterial sulfite dehydrogenases in organotrophic metabolism: separation and identification in Cupriavidus necator H16 and in Delftia acidovorans SPH-1. Microbiology (Reading, England) 28 18174144
2010 Hypoxia-inducible factor regulation of ANK expression in nucleus pulposus cells: possible implications in controlling dystrophic mineralization in the intervertebral disc. Arthritis and rheumatism 27 20496369
1998 High frequency of de novo mutations in ankyrin gene (ANK1) in children with hereditary spherocytosis. The Journal of pediatrics 27 9470011
2018 A polydnavirus-encoded ANK protein has a negative impact on steroidogenesis and development. Insect biochemistry and molecular biology 25 29559251
2008 Vanin-1 pantetheinase drives increased chondrogenic potential of mesenchymal precursors in ank/ank mice. The American journal of pathology 25 18187567
2002 Identification of Ank(G107), a muscle-specific ankyrin-G isoform. The Journal of biological chemistry 25 11796721
2010 The inorganic pyrophosphate transporter ANK preserves the differentiated phenotype of articular chondrocyte. The Journal of biological chemistry 24 20133941
2009 Structure and mechanical properties of Ank/Ank mutant mouse dental tissues--an animal model for studying periodontal regeneration. Archives of oral biology 24 19338977
2003 Progressive ankylosis (Ank) protein is expressed by neurons and Ank immunohistochemical reactivity is increased by limbic seizures. Laboratory investigation; a journal of technical methods and pathology 24 12861042
1996 Ankyrin Napoli: a de novo deletional frameshift mutation in exon 16 of ankyrin gene (ANK1) associated with spherocytosis. British journal of haematology 24 8703812
2010 A novel ENU-generated truncation mutation lacking the spectrin-binding and C-terminal regulatory domains of Ank1 models severe hemolytic hereditary spherocytosis. Experimental hematology 23 21193012
1997 Frequent de novo mutations of the ANK1 gene mimic a recessive mode of transmission in hereditary spherocytosis: three new ANK1 variants: ankyrins Bari, Napoli II and Anzio. British journal of haematology 22 9054656
1994 Rat interleukin-2-activated natural killer (A-NK) cell-mediated lysis is determined by the presence of CD18 on A-NK cells and the absence of major histocompatibility complex class I on target cells. European journal of immunology 22 7912675
2005 FGF2 alters expression of the pyrophosphate/phosphate regulating proteins, PC-1, ANK and TNAP, in the calvarial osteoblastic cell line, MC3T3E1(C4). Connective tissue research 21 16546821
2021 The histone modification H3K4me3 is altered at the ANK1 locus in Alzheimer's disease brain. Future science OA 19 33815817
2014 The novel pterostilbene derivative ANK-199 induces autophagic cell death through regulating PI3 kinase class III/beclin 1/Atg‑related proteins in cisplatin‑resistant CAR human oral cancer cells. International journal of oncology 19 24889814
2013 Continuous cyclic mechanical tension increases ank expression in endplate chondrocytes through the TGF-β1 and p38 pathway. European journal of histochemistry : EJH 19 24085277
2008 Localization of ank1.5 in the sarcoplasmic reticulum precedes that of SERCA and RyR: relationship with the organization of obscurin in developing sarcomeres. Histochemistry and cell biology 19 19002483
2014 A polydnavirus ANK protein acts as virulence factor by disrupting the function of prothoracic gland steroidogenic cells. PloS one 18 24743267
1996 Generation of activated natural killer (A-NK) cells in patients with chronic myelogenous leukaemia and their role in the in vitro disappearance of BCR/abl-positive targets. British journal of haematology 18 8639431
2024 ANK Deficiency-Mediated Cytosolic Citrate Accumulation Promotes Aortic Aneurysm. Circulation research 17 39513269
1993 Distinct fetal Ank-1 and Ank-2 related proteins and mRNAs in normal and nb/nb mice. Blood 17 8471772
2014 The role of ANK interactions with MYBBP1a and SPHK1 in catabolic events of articular chondrocytes. Osteoarthritis and cartilage 16 24747173
2009 Nuclear accumulation of the ankyrin repeat protein ANK1 enhances the auxin-mediated transcription accomplished by the bZIP transcription factors BZI-1 and BZI-2. The Plant journal : for cell and molecular biology 16 19220790
2007 Expression and localisation of the pyrophosphate transporter, ANK, in murine kidney cells. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 16 17762177
2006 P5L mutation in Ank results in an increase in extracellular inorganic pyrophosphate during proliferation and nonmineralizing hypertrophy in stably transduced ATDC5 cells. Arthritis research & therapy 16 17067391
2023 Loss of function mutation in Ank causes aberrant mineralization and acquisition of osteoblast-like-phenotype by the cells of the intervertebral disc. Cell death & disease 15 37468461
2017 ANK1 and DnaK-TPR, Two Tetratricopeptide Repeat-Containing Proteins Primarily Expressed in Toxoplasma Bradyzoites, Do Not Contribute to Bradyzoite Differentiation. Frontiers in microbiology 15 29180989
2012 A de novo interstitial deletion of 8p11.2 including ANK1 identified in a patient with spherocytosis, psychomotor developmental delay, and distinctive facial features. Gene 15 22771917
2008 Progressive ankylosis gene (ank) regulates osteoblast differentiation. Cells, tissues, organs 15 18728347
1999 Endogenous and adoptively transferred A-NK and T-LAK cells continuously accumulate within murine metastases up to 48 h after inoculation. In vivo (Athens, Greece) 15 10459491
1998 Infiltration patterns of short- and long-term cultured A-NK and T-LAK cells following adoptive immunotherapy. Scandinavian journal of immunology 15 9652820
2022 A NAC Transcription Factor TuNAC69 Contributes to ANK-NLR-WRKY NLR-Mediated Stripe Rust Resistance in the Diploid Wheat Triticum urartu. International journal of molecular sciences 14 35008990
2010 Three novel mutations in the ANK membrane protein cause craniometaphyseal dysplasia with variable conductive hearing loss. American journal of medical genetics. Part A 14 20358596
2009 Oxygen tension regulates the expression of ANK (progressive ankylosis) in an HIF-1-dependent manner in growth plate chondrocytes. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 14 19419319
2003 Normoblastosis, a murine model for ankyrin-deficient hemolytic anemia, is caused by a hypomorphic mutation in the erythroid ankyrin gene Ank1. The hematology journal : the official journal of the European Haematology Association 14 14671619
2015 Association of Single-Nucleotide Polymorphism in ANK1 with Late-Onset Alzheimer's Disease in Han Chinese. Molecular neurobiology 13 26611832
2007 Targeting of products of genes to tumor sites using adoptively transferred A-NK and T-LAK cells. Cancer gene therapy 13 17273184
1996 Immunocytochemical localization of multicatalytic protease complex (proteasome) during generation of murine IL-2-activated natural killer (A-NK) cells. European journal of cell biology 13 8980912
1996 Expression and function of LFA-1 on A-NK and T-LAK cells: role in tumor target killing and migration into tumor tissue. Natural immunity 13 9162263
2020 Comparative analysis of ankyrin (ANK) genes of five capripoxviruses isolate strains from Xinjiang province in China. Virology journal 12 32859219
2019 Two novel ANK1 loss-of-function mutations in Chinese families with hereditary spherocytosis. Journal of cellular and molecular medicine 12 31016877
2017 The role of the progressive ankylosis protein (ANK) in adipogenic/osteogenic fate decision of precursor cells. Bone 12 28286238
2012 Aberrant chondrocyte hypertrophy and activation of β-catenin signaling precede joint ankylosis in ank/ank mice. The Journal of rheumatology 12 22298904
2010 Phosphate and calcium are required for TGFbeta-mediated stimulation of ANK expression and function during chondrogenesis. Journal of cellular physiology 12 20432454
1997 Apparently normal ankyrin content in unsplenectomized hereditary spherocytosis patients with the inactivation of one ankyrin (ANK1) allele. Haematologica 12 9234582
2017 Association of ANK1 variants with new-onset type 2 diabetes in a Han Chinese population from northeast China. Experimental and therapeutic medicine 11 28912869
2015 Identification of a novel p.Q1772X ANK1 mutation in a Korean family with hereditary spherocytosis. PloS one 11 26107955
2001 Modulation of A-NK cell rigidity: In vitro characterization and in vivo implications for cell delivery. Biorheology 11 11381172
2017 The ANK repeats of Notch-4/Int3 activate NF-κB canonical pathway in the absence of Rbpj and causes mammary tumorigenesis. Scientific reports 10 29057904
2017 Identification of a novel de novo ANK1 R1426* nonsense mutation in a Chinese family with hereditary spherocytosis by NGS. Oncotarget 10 29228571
2016 The progressive ankylosis protein ANK facilitates clathrin- and adaptor-mediated membrane traffic at the trans-Golgi network-to-endosome interface. Human molecular genetics 10 27466194
2013 JNK phosphorylation promotes natural degeneration of cervical endplate chondrocytes by down-regulating expression of ANK. European review for medical and pharmacological sciences 10 24065227
2003 Targeting of the AE2 anion exchanger to the Golgi apparatus is cell type-dependent and correlates with the expression of Ank(195), a Golgi membrane skeletal protein. FEBS letters 10 12832051
2000 HLA-B27 has no effect on the phenotypic expression of progressive ankylosis in ank/ank mice. The Journal of rheumatology 10 10813297