Ankyrin-2 (ANK2)
The protein contains 3957 amino acids for an estimated molecular weight of 433715 Da.
Plays an essential role in the localization and membrane stabilization of ion transporters and ion channels in several cell types, including cardiomyocytes, as well as in striated muscle cells. In skeletal muscle, required for proper localization of DMD and DCTN4 and for the formation and/or stability of a special subset of microtubules associated with costameres and neuromuscular junctions. In cardiomyocytes, required for coordinate assembly of Na/Ca exchanger, SLC8A1/NCX1, Na/K ATPases ATP1A1 and ATP1A2 and inositol 1,4,5-trisphosphate (InsP3) receptors at sarcoplasmic reticulum/sarcolemma sites. Required for expression and targeting of SPTBN1 in neonatal cardiomyocytes and for the regulation of neonatal cardiomyocyte contraction rate (PubMed:12571597). In the inner segment of rod photoreceptors, required for the coordinated expression of the Na/K ATPase, Na/Ca exchanger and beta-2-spectrin (SPTBN1) (By similarity). Plays a role in endocytosis and intracellular protein transport. Associates with phosphatidylinositol 3-phosphate (PI3P)-positive organelles and binds dynactin to promote long-range motility of cells. Recruits RABGAP1L to (PI3P)-positive early endosomes, where RABGAP1L inactivates RAB22A, and promotes polarized trafficking to the leading edge of the migrating cells. Part of the ANK2/RABGAP1L complex which is required for the polarized recycling of fibronectin receptor ITGA5 ITGB1 to the plasma membrane that enables continuous directional cell migration (By simi (updated: Dec. 5, 2018)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- 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.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
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.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
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.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.
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Biological Process
Atrial cardiac muscle cell action potential
Atrial cardiac muscle cell to AV node cell communication
Atrial septum development
Axon guidance
Cardiac muscle contraction
Cellular calcium ion homeostasis
Cellular protein localization
Endocytosis
Endoplasmic reticulum to Golgi vesicle-mediated transport
Membrane depolarization during SA node cell action potential
Paranodal junction assembly
Positive regulation of calcium ion transmembrane transporter activity
Positive regulation of calcium ion transport
Positive regulation of cation channel activity
Positive regulation of gene expression
Positive regulation of potassium ion transmembrane transporter activity
Positive regulation of potassium ion transport
Protein localization to cell surface
Protein localization to endoplasmic reticulum
Protein localization to M-band
Protein localization to organelle
Protein localization to plasma membrane
Protein localization to T-tubule
Protein stabilization
Protein targeting to plasma membrane
Protein transport
Regulation of atrial cardiac muscle cell action potential
Regulation of calcium ion transmembrane transporter activity
Regulation of calcium ion transport
Regulation of cardiac muscle cell contraction
Regulation of cardiac muscle cell membrane potential
Regulation of cardiac muscle contraction
Regulation of cardiac muscle contraction by calcium ion signaling
Regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion
Regulation of heart rate
Regulation of heart rate by cardiac conduction
Regulation of protein stability
Regulation of release of sequestered calcium ion into cytosol
Regulation of SA node cell action potential
Regulation of ventricular cardiac muscle cell membrane repolarization
Response to methylmercury
SA node cell action potential
SA node cell to atrial cardiac muscle cell communication
Sarcoplasmic reticulum calcium ion transport
T-tubule organization
Ventricular cardiac muscle cell action potential
Cellular Component
A band
Apical plasma membrane
Axon initial segment
Basolateral plasma membrane
Costamere
Cytoskeleton
Cytosol
Early endosome
Integral component of plasma membrane
Intercalated disc
Intracellular anatomical structure
Lysosome
M band
Membrane
Membrane raft
Mitochondrion
Neuron projection
Obsolete cell
Perinuclear region of cytoplasm
Plasma membrane
Postsynaptic membrane
Recycling endosome
Sarcolemma
T-tubule
Z disc
The reference OMIM entry for this protein is 106410
Ankyrin 2; ank2
Ankyrin, nonerythroid
Ankyrin, brain
Ankyrin, neuronal
Ankyrin-b
CLONING
Tse et al. (1991) studied immunoreactive isoforms of erythrocyte ankyrin found in nonerythroid tissues. Using an erythrocyte ankyrin cDNA clone as a hybridization probe, they isolated a clone from a human genomic library that hybridized at low but not at high stringency. Further studies suggested that the clone represented part of a gene for nonerythroid ankyrin, which they designated ANK2. Otto et al. (1991) isolated and sequenced cDNAs related to 2 brain ankyrin isoforms and showed that they are produced through alternative splicing of the mRNA from a single gene.GENE STRUCTURE
The ANK2 gene contains 46 exons (Mohler et al., 2007). Exon 38 is brain-specific.GENE FUNCTION
The axon initial segment (AIS) is the site at which neural signals arise, and should be the most efficient site to regulate neural activity. Kuba et al. (2010) reported that deprivation of auditory input in an avian brainstem auditory neuron leads to an increase in AIS length, thus augmenting the excitability of the neuron. The length of the AIS, defined by the distribution of voltage-gated sodium channels and the AIS anchoring protein, ankyrin G, increased by 1.7 times in 7 days after auditory input deprivation. This was accompanied by an increase in the whole-cell sodium current, membrane excitability, and spontaneous firing. Kuba et al. (2010) concluded that their work demonstrated homeostatic regulations of the AIS, which may contribute to the maintenance of the auditory pathway after hearing loss. Furthermore, plasticity at the spike initiation site suggests a powerful pathway for refining neuronal computation in the face of strong sensory deprivation.MAPPING
By analysis of somatic cell hybrids and by fluorescence in situ hybridization, Tse et al. (1991) assigned the ANK2 gene to 4q25-q27. By analysis of human/rodent cell hybrids, Otto et al. (1991) assigned the brain ankyrin gene to chromosome 4.MOLECULAR GENETICS
Schott et al. (1995) characterized a large French kindred with long QT syndrome associated with sinus node dysfunction and episodes of atrial fibrillation segregating as an autosomal dominant trait. They mapped the disorder to an 18-cM interval on 4q25-q27 (LQT4; 600919). Mohler et al. (2003) sequenced the ANK2 gene, which maps to the same region, and identified a glu1425-to-gly (E1425G) missense mutation (106410.0001). Ankyrin-B appears to be the first identified protein to be implicated in a congenital long QT syndrome that is not an ion channel or channel subunit. Mohler et al. (2004) identified 8 unrelated probands harboring 5 different ankyrin-B loss-of-function mutations (106410.0001-106410.0005), 4 of which were previously undescribed, and expanded the phenotype previously described by Schott et al. (1995). Mohler et al. (2004) found that humans with ankyrin-B mutations display varying degrees of cardiac dysfunction, including bradycardia, sinus arrhythmia, idiopathic ventricular fibrillation, catecholaminergic polymorphic ventricular tachycardia, and risk of sudden death. However, a prolonged rate-corrected QT interval was not a consistent feature, indicating that ankyrin-B dysfunction represents a clinical entity distinct from classic long QT syndromes. The mutations were localized in the ankyrin-B regulatory domain, which distinguishes function of ankyrin-B from ankyrin-G (ANK3; 600465) in cardiomyocytes. All mutations abolished ability of ankyrin-B to restore abnormal Ca(2+) ... More on the omim web site
Dec. 9, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 5, 2018: 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 ANK2
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 106410 was added.
Jan. 27, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed