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Tbio Ankyrin-1

Isoform Mu17 together with obscurin in skeletal muscle may provide a molecular link between the sarcoplasmic reticulum and myofibrils.

Ankyrins are a family of proteins that link the integral membrane proteins to the underlying spectrin-actin cytoskeleton and play key roles in activities such as cell motility, activation, proliferation, contact and the maintenance of specialized membrane domains. Multiple isoforms of ankyrin with different affinities for various target proteins are expressed in a tissue-specific, developmentally regulated manner. Most ankyrins are typically composed of three structural domains: an amino-terminal domain containing multiple ankyrin repeats; a central region with a highly conserved spectrin binding domain; and a carboxy-terminal regulatory domain which is the least conserved and subject to variation. Ankyrin 1, the prototype of this family, was first discovered in the erythrocytes, but since has also been found in brain and muscles. Mutations in erythrocytic ankyrin 1 have been associated in approximately half of all patients with hereditary spherocytosis. Complex patterns of alternative splicing in the regulatory domain, giving rise to different isoforms of ankyrin 1 have been described. Truncated muscle-specific isoforms of ankyrin 1 resulting from usage of an alternate promoter have also been identified. [provided by RefSeq, Dec 2008]

 Comments

Property Summary

NCBI Gene PubMed Count 73
PubMed Score 289.86
PubTator Score 246.05

Knowledge Summary

Patent

No data available

TINX Plot

  Disease (8)

Disease Target Count Z-score Confidence
Carcinoma 2147 0.0 1.0
Disease Target Count Z-score Confidence
Type 2 diabetes mellitus 192 0.0 2.0
Disease Target Count Z-score Confidence
Hereditary elliptocytosis 20 4.345 2.2
Congenital hemolytic anemia 31 0.0 4.0
Disease Target Count Z-score Confidence
Werner syndrome 29 3.205 1.6
Disease Target Count
Spherocytosis 1 1

Expression

  Differential Expression (11)

Disease log2 FC p
osteosarcoma -5.166 1.4e-07
ependymoma -2.100 5.1e-12
glioblastoma -1.800 8.5e-08
sonic hedgehog group medulloblastoma -1.300 1.3e-02
cystic fibrosis -1.777 7.4e-06
atypical teratoid / rhabdoid tumor -1.700 1.9e-05
primitive neuroectodermal tumor -1.200 1.6e-02
acute quadriplegic myopathy -1.134 5.3e-06
adult high grade glioma -1.900 3.0e-04
pilocytic astrocytoma -1.600 8.0e-05
subependymal giant cell astrocytoma -2.142 7.3e-03

Synonym

Accession P16157 A0PJN8 A6NJ23 E5RFL7 O43400 Q13768 Q53ER1 Q59FP2 Q8N604 Q99407 ANK-1
Symbols ANK
SPH1
SPH2

Gene

ANK1

PANTHER Protein Class (1)

PDB

3KBT   3KBU   1N11   2YQF   2YVI   3F59   3UD1   3UD2  

  Ortholog (2)

Species Source Disease
Chimp OMA EggNOG
Mouse OMA EggNOG Inparanoid Hereditary spherocytosis [JensenLab Knowledge GHR]
Hereditary spherocytosis [JensenLab Text Mining]
Hereditary spherocytosis [Monarch]
Congenital hemolytic anemia [JensenLab Knowledge UniProtKB-KW]
Hereditary elliptocytosis [JensenLab Knowledge UniProtKB-KW]
Hereditary elliptocytosis [JensenLab Text Mining]

 UniProt Keyword (19)

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 GO Function (6)

 GO Component (13)

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 GO Process (7)

 Compartment GO Term (44)

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 OMIM Phenotype (1)

 MGI Phenotype (16)

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 GWAS Trait (3)

 HCA RNA Cell Line (54)

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Pathway (16)

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Protein-protein Interaction (79)

DCTN6   CHL1   DYNC1I1   COPE   GOSR2   SPTBN2   BET1   YKT6   DYNC1LI2   KCNQ3   KCNQ2   USO1   DCTN3   NFASC   GOSR1   INS   SPTA1   CD55   SPTB   CD59   FOLR1   ARF4   KDELR1   L1CAM   COPB2   ARCN1   TMED10   COPB1   COPA   COPZ1   DYNLL1   COG7   SPTBN1   ANK2   SCN1B   GOLGA2   TMEM115   ANK3   STX5   DYNC1I2   DCTN2   SPTAN1   DCTN1   DYNC1H1   SCN5A   COG2   GOLGB1   TMED2   ARFGAP2   ARFGAP1   COG1   GBF1   NRCAM   DYNLL2   COG3   COG8   GORASP1   DCTN5   TMED9   RAB1B   SPTBN4   COG4   ARFGAP3   SPTBN5   BET1L   COPZ2   COPG2   DCTN4   COG5   COG6   TMED7   TMED3   COPG1   DYNC1LI1   NELFB   PIKFYVE   VAC14   PDS5B   FIG4  

Gene RIF (31)

PMID Text
26107955 analysis of a novel p.Q1772X ANK1 mutation in a Korean family with hereditary spherocytosis [case report of two family members]
25129077 We identified a differentially methylated region in the ankyrin 1 (ANK1) gene that was associated with neuropathology in the entorhinal cortex, a primary site of Alzheimer disease manifestation.
25129075 Our analyses suggest that these DNA methylation changes may have a role in the onset of Alzheimer disease given that we observed them in presymptomatic subjects and that six of the validated genes connect to a known susceptibility gene network.
24903897 A novel L1340P mutation in the ANK1 gene is associated with hereditary spherocytosis.
24758720 The study reports the refinement for a protein heterodimer complex using limited EPR spectroscopic data and a rigid-body docking algorithm: a three-dimensional model for an ankyrin 1-BND3 complex.
23457408 ANK1 rs516946 confers impaired insulin release.
23013433 The ankyrin-binding site on band 3 is located near the deoxygenated hemoglobin-binding site, therefore following deoxygenation ankyrin is displaced from band 3.
22968456 A tissue-specific chromatin loop brings NF-E2 and ANK1E into close proximity preventing gene silencing and mutagenesis leading to hereditary spherocytosis.
22573887 The interaction of KCTD6 with ankyrin-1 may have implications beyond muscle for hereditary spherocytosis, as KCTD6 is also present in erythrocytes, and erythrocyte ankyrin isoforms contain its mapped minimal binding site.
22456796 results indicate that the ANK1 locus is a new, common susceptibility locus for type 2 diabetes across different ethnic groups
22348230 Ankyrin binds to the N-terminal region (residues 132-241) of the CA domain of HIV-1 Gag. Ankyrin decreases expression of Gag in HIV-1-infected SupT1 cells
21493712 Determination of structural models of the complex between the cytoplasmic domain of erythrocyte band 3 and ankyrin-R repeats 13-24.
21177872 cytoskeletal ankyrin family are substrates for FIH-catalyzed hydroxylations
21099109 a region upstream of the promoter is a barrier insulator. The region exhibited functional and structural characteristics of a barrier, including prevention of gene silencing, appropriate chromatin configuration and occupancy by barrier-associated proteins
21071415 The Hereditary Spherocytosis mutation in the human Ankyrin-1 promoter disrupted the binding of the transcription factor TFIID, the major component of the pre-initiation complex.
20858683 Observational study, meta-analysis, and genome-wide association study of gene-disease association. (HuGE Navigator)
20479128 Generated a library of more than 16,000 ANK-1 promoters with degenerate sequence around the dinucleotide deletion mutation and cloned the functional promoter sequences. Identified the wild type and three additional sequences, and derived a consensus.
20379614 Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
18987618 Observational study and genome-wide association study of gene-disease association. (HuGE Navigator)
18768923 Ankyrin facilitates intracellular trafficking of alpha1-Na+-K+-ATPase in polarized cells.
17720975 Structural and mutational studies of the binding region on small Ank1 for obscurin suggest that it consists of two ankyrin repeats with very similar structures.
17716929 Our results therefore indicate the importance of N-terminal region for lipid-binding activity of the beta-spectrin ankyrin-binding domain and its substantial role in maintaining the spectrin-based skeleton distribution.
17520478 It was shown that the region within beta-spectrin involved in interactions with ankyrin includes a lipid-binding site and binding is inhibited by ankyrin. Our results shows: the ankyrin-sens. lipid-bind. site of beta-spectrin exhibits a helical conform.
17128827 Observational study of gene-disease association. (HuGE Navigator)
17128827 Allelic and genotypic frequencies were similar in both studied groups for the G199A and Memphis I polymorphismsin Hereditary Spherocytosis among the Mexican population.
16762928 off rates of the band 3-ankyrin interaction are sufficiently slow to allow sustained erythrocyte deformation without loss of elasticity
16718373 The interactions of three protein 4.2-derived recombinant proteins with CDB3 and ankyrin were investigated by using Far-Western blot and pull-down assay.
15040428 identification of ankyrin as a target of spectrin's E2/E3 activity
12527750 A small muscle-specific isoform of the ANK1 gene, ank1.5, interacts with obscurin. Since ank1.5 is localised on the sarcoplasmic reticulum and obscurin on the myofibrils, these two proteins may provide a molecular link between these subcellular regions.
12444090 interaction of hydrophilic domain with two N-terminal immunoglobulin domains of titin
12130521 ankyrin and protein 4.1 are cleaved by native and recombinant falcipain-2 near their C-termini

AA Sequence 

MPYSVGFREADAATSFLRAARSGNLDKALDHLRNGVDINTCNQNGLNGLHLASKEGHVKMVVELLHKEII      1 - 70
LETTTKKGNTALHIAALAGQDEVVRELVNYGANVNAQSQKGFTPLYMAAQENHLEVVKFLLENGANQNVA     71 - 140
TEDGFTPLAVALQQGHENVVAHLINYGTKGKVRLPALHIAARNDDTRTAAVLLQNDPNPDVLSKTGFTPL    141 - 210
HIAAHYENLNVAQLLLNRGASVNFTPQNGITPLHIASRRGNVIMVRLLLDRGAQIETKTKDELTPLHCAA    211 - 280
RNGHVRISEILLDHGAPIQAKTKNGLSPIHMAAQGDHLDCVRLLLQYDAEIDDITLDHLTPLHVAAHCGH    281 - 350
HRVAKVLLDKGAKPNSRALNGFTPLHIACKKNHVRVMELLLKTGASIDAVTESGLTPLHVASFMGHLPIV    351 - 420
KNLLQRGASPNVSNVKVETPLHMAARAGHTEVAKYLLQNKAKVNAKAKDDQTPLHCAARIGHTNMVKLLL    421 - 490
ENNANPNLATTAGHTPLHIAAREGHVETVLALLEKEASQACMTKKGFTPLHVAAKYGKVRVAELLLERDA    491 - 560
HPNAAGKNGLTPLHVAVHHNNLDIVKLLLPRGGSPHSPAWNGYTPLHIAAKQNQVEVARSLLQYGGSANA    561 - 630
ESVQGVTPLHLAAQEGHAEMVALLLSKQANGNLGNKSGLTPLHLVAQEGHVPVADVLIKHGVMVDATTRM    631 - 700
GYTPLHVASHYGNIKLVKFLLQHQADVNAKTKLGYSPLHQAAQQGHTDIVTLLLKNGASPNEVSSDGTTP    701 - 770
LAIAKRLGYISVTDVLKVVTDETSFVLVSDKHRMSFPETVDEILDVSEDEGEELISFKAERRDSRDVDEE    771 - 840
KELLDFVPKLDQVVESPAIPRIPCAMPETVVIRSEEQEQASKEYDEDSLIPSSPATETSDNISPVASPVH    841 - 910
TGFLVSFMVDARGGSMRGSRHNGLRVVIPPRTCAAPTRITCRLVKPQKLSTPPPLAEEEGLASRIIALGP    911 - 980
TGAQFLSPVIVEIPHFASHGRGDRELVVLRSENGSVWKEHRSRYGESYLDQILNGMDEELGSLEELEKKR    981 - 1050
VCRIITTDFPLYFVIMSRLCQDYDTIGPEGGSLKSKLVPLVQATFPENAVTKRVKLALQAQPVPDELVTK   1051 - 1120
LLGNQATFSPIVTVEPRRRKFHRPIGLRIPLPPSWTDNPRDSGEGDTTSLRLLCSVIGGTDQAQWEDITG   1121 - 1190
TTKLVYANECANFTTNVSARFWLSDCPRTAEAVNFATLLYKELTAVPYMAKFVIFAKMNDPREGRLRCYC   1191 - 1260
MTDDKVDKTLEQHENFVEVARSRDIEVLEGMSLFAELSGNLVPVKKAAQQRSFHFQSFRENRLAMPVKVR   1261 - 1330
DSSREPGGSLSFLRKAMKYEDTQHILCHLNITMPPCAKGSGAEDRRRTPTPLALRYSILSESTPGSLSGT   1331 - 1400
EQAEMKMAVISEHLGLSWAELARELQFSVEDINRIRVENPNSLLEQSVALLNLWVIREGQNANMENLYTA   1401 - 1470
LQSIDRGEIVNMLEGSGRQSRNLKPDRRHTDRDYSLSPSQMNGYSSLQDELLSPASLGCALSSPLRADQY   1471 - 1540
WNEVAVLDAIPLAATEHDTMLEMSDMQVWSAGLTPSLVTAEDSSLECSKAEDSDATGHEWKLEGALSEEP   1541 - 1610
RGPELGSLELVEDDTVDSDATNGLIDLLEQEEGQRSEEKLPGSKRQDDATGAGQDSENEVSLVSGHQRGQ   1611 - 1680
ARITHSPTVSQVTERSQDRLQDWDADGSIVSYLQDAAQGSWQEEVTQGPHSFQGTSTMTEGLEPGGSQEY   1681 - 1750
EKVLVSVSEHTWTEQPEAESSQADRDRRQQGQEEQVQEAKNTFTQVVQGNEFQNIPGEQVTEEQFTDEQG   1751 - 1820
NIVTKKIIRKVVRQIDLSSADAAQEHEEVTVEGPLEDPSELEVDIDYFMKHSKDHTSTPNP            1821 - 1881
//

Text Mined References (83)

PMID Year Title
26107955 2015 Identification of a novel p.Q1772X ANK1 mutation in a Korean family with hereditary spherocytosis.
25129077 2014 Methylomic profiling implicates cortical deregulation of ANK1 in Alzheimer's disease.
25129075 2014 Alzheimer's disease: early alterations in brain DNA methylation at ANK1, BIN1, RHBDF2 and other loci.
24903897 2014 A novel L1340P mutation in the ANK1 gene is associated with hereditary spherocytosis?
24758720 2014 Automated structure refinement for a protein heterodimer complex using limited EPR spectroscopic data and a rigid-body docking algorithm: a three-dimensional model for an ankyrin-CDB3 complex.
24647736 2014 Multiple nonglycemic genomic loci are newly associated with blood level of glycated hemoglobin in East Asians.
24509480 2014 Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility.
24275569 2014 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
23457408 2013 Type 2 diabetes risk alleles near BCAR1 and in ANK1 associate with decreased ?-cell function whereas risk alleles near ANKRD55 and GRB14 associate with decreased insulin sensitivity in the Danish Inter99 cohort.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
23013433 2013 Oxygen regulates the band 3-ankyrin bridge in the human erythrocyte membrane.
22968456 2012 A tissue-specific chromatin loop activates the erythroid ankyrin-1 promoter.
22573887 2012 Obscurin and KCTD6 regulate cullin-dependent small ankyrin-1 (sAnk1.5) protein turnover.
22456796 2012 A single-nucleotide polymorphism in ANK1 is associated with susceptibility to type 2 diabetes in Japanese populations.
22424883 2012 Genome-wide association study of lung function decline in adults with and without asthma.
22310050 2012 Structurally similar but functionally diverse ZU5 domains in human erythrocyte ankyrin.
21493712 2011 Determination of structural models of the complex between the cytoplasmic domain of erythrocyte band 3 and ankyrin-R repeats 13-24.
21269460 2011 Initial characterization of the human central proteome.
21177872 2011 Asparagine and aspartate hydroxylation of the cytoskeletal ankyrin family is catalyzed by factor-inhibiting hypoxia-inducible factor.
21099109 2010 Mutation of a barrier insulator in the human ankyrin-1 gene is associated with hereditary spherocytosis.
21071415 2011 Genome-wide detection of a TFIID localization element from an initial human disease mutation.
20858683 2010 Common variants at 10 genomic loci influence hemoglobin A?(C) levels via glycemic and nonglycemic pathways.
20479128 2010 Functional analysis of a novel cis-acting regulatory region within the human ankyrin gene (ANK-1) promoter.
20379614 Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
18987618 2009 Screening for replication of genome-wide SNP associations in sporadic ALS.
18768923 2008 Ankyrin facilitates intracellular trafficking of alpha1-Na+-K+-ATPase in polarized cells.
18669648 2008 A quantitative atlas of mitotic phosphorylation.
18088087 2008 Phosphoproteome of resting human platelets.
17720975 2007 Mapping the binding site on small ankyrin 1 for obscurin.
17716929 2007 Lipid-binding role of betaII-spectrin ankyrin-binding domain.
17520478 Structural insight into an ankyrin-sensitive lipid-binding site of erythroid beta-spectrin.
17207965 2007 hORFeome v3.1: a resource of human open reading frames representing over 10,000 human genes.
17128827 [Polymorphism analysis of G199A, Ncol in ANK1 and Memphis I in SLC4A1 genes in Mexican healthy individuals and subjects affected with hereditary spherocytosis].
16962094 2006 Molecular interactions with obscurin are involved in the localization of muscle-specific small ankyrin1 isoforms to subcompartments of the sarcoplasmic reticulum.
16959974 2006 The consensus coding sequences of human breast and colorectal cancers.
16762928 2006 Rate of rupture and reattachment of the band 3-ankyrin bridge on the human erythrocyte membrane.
16718373 2006 Associations of protein 4.2 with band 3 and ankyrin.
16597699 2006 MAP kinase pathway-dependent phosphorylation of the L1-CAM ankyrin binding site regulates neuronal growth.
16580865 Functional interaction between Rh proteins and the spectrin-based skeleton in erythroid and epithelial cells.
16421571 2006 DNA sequence and analysis of human chromosome 8.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15051494 2004 CD44 interaction with ankyrin and IP3 receptor in lipid rafts promotes hyaluronan-mediated Ca2+ signaling leading to nitric oxide production and endothelial cell adhesion and proliferation.
15040428 2004 Ankyrin is a target of spectrin's E2/E3 ubiquitin-conjugating/ligating activity.
12719424 2003 Rh-RhAG/ankyrin-R, a new interaction site between the membrane bilayer and the red cell skeleton, is impaired by Rh(null)-associated mutation.
12631729 2003 Obscurin is a ligand for small ankyrin 1 in skeletal muscle.
12527750 2003 Binding of an ankyrin-1 isoform to obscurin suggests a molecular link between the sarcoplasmic reticulum and myofibrils in striated muscles.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12456646 2002 Crystal structure of a 12 ANK repeat stack from human ankyrinR.
12444090 2003 The hydrophilic domain of small ankyrin-1 interacts with the two N-terminal immunoglobulin domains of titin.
12409278 2003 Dissociation of spectrin-ankyrin complex as a basis for loss of Na-K-ATPase polarity after ischemia.
12130521 2002 Plasmodium falciparum cysteine protease falcipain-2 cleaves erythrocyte membrane skeletal proteins at late stages of parasite development.
12019270 2002 BLOC-1, a novel complex containing the pallidin and muted proteins involved in the biogenesis of melanosomes and platelet-dense granules.
11427698 2001 Spectrin and ankyrin-based pathways: metazoan inventions for integrating cells into tissues.
11372755 2001 Ankyrin gene mutations in japanese patients with hereditary spherocytosis.
11222639 2001 Cytoplasmic domain mutations of the L1 cell adhesion molecule reduce L1-ankyrin interactions.
11102985 2000 Low frequency of ankyrin mutations in hereditary spherocytosis: identification of three novel mutations.
10910934 2000 The human ankyrin-1 gene is selectively transcribed in erythroid cell lines despite the presence of a housekeeping-like promoter.
10893266 2000 Ankyrin-Tiam1 interaction promotes Rac1 signaling and metastatic breast tumor cell invasion and migration.
9804856 1998 Structural requirements for association of neurofascin with ankyrin.
9628825 1998 An alternative first exon in the distal end of the erythroid ankyrin gene leads to production of a small isoform containing an NH2-terminal membrane anchor.
9587054 1998 Anion exchanger 2 (AE2) binds to erythrocyte ankyrin and is colocalized with ankyrin along the basolateral plasma membrane of human gastric parietal cells.
9430667 1998 An alternate promoter directs expression of a truncated, muscle-specific isoform of the human ankyrin 1 gene.
9235914 1997 Structure and organization of the human ankyrin-1 gene. Basis for complexity of pre-mRNA processing.
9024692 1997 Small, membrane-bound, alternatively spliced forms of ankyrin 1 associated with the sarcoplasmic reticulum of mammalian skeletal muscle.
8703812 1996 Ankyrin Napoli: a de novo deletional frameshift mutation in exon 16 of ankyrin gene (ANK1) associated with spherocytosis.
8681137 1996 Identification of 4370 expressed sequence tags from a 3'-end-specific cDNA library of human skeletal muscle by DNA sequencing and filter hybridization.
8640229 1996 Ankyrin-1 mutations are a major cause of dominant and recessive hereditary spherocytosis.
8385102 1993 The involvement of ankyrin in the regulation of inositol 1,4,5-trisphosphate receptor-mediated internal Ca2+ release from Ca2+ storage vesicles in mouse T-lymphoma cells.
8227202 1993 Association of the brain anion exchanger, AE3, with the repeat domain of ankyrin.
8159688 1994 Ankyrin binds to two distinct cytoplasmic domains of Na,K-ATPase alpha subunit.
8125298 1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.
7665627 1995 The ANK repeats of erythrocyte ankyrin form two distinct but cooperative binding sites for the erythrocyte anion exchanger.
7505012 1993 Hyaluronic acid-induced lymphocyte signal transduction and HA receptor (GP85/CD44)-cytoskeleton interaction.
6449514 1980 Reassociation of ankyrin with band 3 in erythrocyte membranes and in lipid vesicles.
2971657 1988 Ankyrin-independent membrane protein-binding sites for brain and erythrocyte spectrin.
2970468 1988 Phosphorylation of ankyrin down-regulates its cooperative interaction with spectrin and protein 3.
2968981 1988 Associations of human erythrocyte band 4.2. Binding to ankyrin and to the cytoplasmic domain of band 3.
2141335 1990 Mapping the binding sites of human erythrocyte ankyrin for the anion exchanger and spectrin.
2137557 1990 Analysis of cDNA for human erythrocyte ankyrin indicates a repeated structure with homology to tissue-differentiation and cell-cycle control proteins.
1833445 1991 Immunocytochemical localization of fodrin and ankyrin in bovine chromaffin cells in vitro.
1689849 1990 cDNA sequence for human erythrocyte ankyrin.
492324 1979 Immunoreactive forms of human erythrocyte ankyrin are present in diverse cells and tissues.
379653 1979 The membrane attachment protein for spectrin is associated with band 3 in human erythrocyte membranes.