Ankyrin-3 (ANK3)

The protein contains 4377 amino acids for an estimated molecular weight of 480410 Da.

 

In skeletal muscle, required for costamere localization of DMD and betaDAG1 (By similarity). Membrane-cytoskeleton linker. May participate in the maintenance/targeting of ion channels and cell adhesion molecules at the nodes of Ranvier and axonal initial segments. Regulates KCNA1 channel activity in function of dietary Mg(2+) levels, and thereby contributes to the regulation of renal Mg(2+) reabsorption (PubMed:23903368).', 'May be part of a Golgi-specific membrane cytoskeleton in association with beta-spectrin. (updated: Dec. 11, 2019)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  3. Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
  4. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  5. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  6. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.


Interpro domains
Total structural coverage: 19%
Model score: 0
No model available.

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VariantDescription
Found in a patient with autism
dbSNP:rs59021407
dbSNP:rs11599164
dbSNP:rs41274672
dbSNP:rs28932171
dbSNP:rs10821668
Found in a patient with autism
Found in a patient with autism
dbSNP:rs12261793
Found in a patient with Gillessen-Kaesbach-Nishimura syndrome

The reference OMIM entry for this protein is 600465

Ankyrin 3; ank3
Ankyrin-g

DESCRIPTION

Ankyrins are peripheral membrane proteins thought to interconnect integral proteins with the spectrin-based membrane skeleton (summary by Kordeli and Bennett, 1991). The ANK3 gene encodes ankyrin-G, which is located mainly at the nodes of Ranvier and the axon initial segment (AIS), 2 subcompartments of neurons responsible for the generation of action potentials. It has been shown to associate with the voltage-dependent sodium channel (summary by Iqbal et al., 2013). Erythrocytic ankyrin, also known as ankyrin-R (ANK1; 612641), and brain ankyrin, also known as ankyrin-B or ankyrin-2 (ANK2; 106410), are distinct forms.

CLONING

Kordeli and Bennett (1991) concluded that the ankyrin isoform present at the node of Ranvier was the product of a previously unidentified ankyrin gene, as ankyrin was still present in the node of Ranvier in ankyrin-R-deficient mice (carrying the nb mutation) and was not recognized by antibodies specific for ankyrin-B or ankyrin-R. Kordeli et al. (1995) described the cDNA sequence of a third ankyrin gene with alternatively spliced isoforms expressed in brain as well as a variety of other tissues. The 2 largest protein isoforms, which contain an unusual serine-rich sequence, are expressed only in nervous tissue. Specific antibodies raised against this serine-rich sequence stained AIS and nodes of Ranvier in cryosections from the rat brain. The full-length polypeptide has a molecular mass of 480 kD and includes a globular head domain, with membrane- and spectrin-binding activities, as well as an extended 'tail' domain. Kordeli et al. (1995) termed the gene ankyrin-G, based on its giant size and general expression. The 2 brain-specific isoforms were of sizes 480 and 270 kD.

GENE FUNCTION

Using GABAergic cell type-specific promoters and mouse BACs, Ango et al. (2004) generated BAC transgenic mice with fluorescence-labeled Purkinje cells and interneurons visible at synaptic resolution during cerebellar development. They found that basket axons always contacted Purkinje soma before innervating Purkinje AIS and prior to the formation of elaborate pinceau synapses. This synapse-targeting process followed the establishment of a subcellular gradient of neurofascin-186 (NF186), an alternatively spliced form of neurofascin (609145) (Davis et al., 1996), along the Purkinje AIS-soma axis. The gradient was dependent on ankyrin-G, an AIS-restricted membrane adaptor protein that recruits NF186. In the absence of the NF186 gradient, basket axons lost directional growth along Purkinje neurons and precisely followed NF186 to ectopic locations. Disruption of NF186-ankyrin-G interactions at AIS reduced pinceau synapse formation. Using coimmunoprecipitation experiments, Mohler et al. (2004) demonstrated that the 190-kD ankyrin-G isoform in adult rat heart associates with the cardiac sodium channel Na(v)1.5, the gene product of the SCN5A gene (600163). By confocal microscopy they showed that ankyrin-G, like Na(v)1.5, is highly expressed at ventricular intercalated disc and T-tubule membranes in cardiomyocytes. Mohler et al. (2004) presented evidence that a human mutation in the SCN5A gene (600163.0033) blocks ankyrin-G binding and disrupts surface expression of Na(v)1.5 in cardiomyocytes, resulting in Brugada syndrome (601144), a dominantly inherited cardiac arrhythmia. Kizhatil et al. (2009) found that targeting of cyclic nucleotide-gated (CNG) channels to the rod outer segment required their in ... More on the omim web site

Subscribe to this protein entry history

Jan. 22, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 25, 2017: Additional information
No protein expression data in P. Mayeux work for ANK3

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 600465 was added.