Voltage-gated potassium channel subunit beta-2 (KCNAB2)
The protein contains 367 amino acids for an estimated molecular weight of 41000 Da.
Cytoplasmic potassium channel subunit that modulates the characteristics of the channel-forming alpha-subunits (PubMed:7649300, PubMed:11825900). Contributes to the regulation of nerve signaling, and prevents neuronal hyperexcitability (By similarity). Promotes expression of the pore-forming alpha subunits at the cell membrane, and thereby increases channel activity (By similarity). Promotes potassium channel closure via a mechanism that does not involve physical obstruction of the channel pore (PubMed:7649300, PubMed:11825900). Promotes KCNA4 channel closure (PubMed:7649300, PubMed:11825900). Modulates the functional properties of KCNA5 (By similarity). Enhances KCNB2 channel activity (By similarity). Binds NADPH and has NADPH-dependent aldoketoreductase activity (By similarity). Has broad substrate specificity and can catalyze the reduction of methylglyoxal, 9,10-phenanthrenequinone, prostaglandin J2, 4-nitrobenzaldehyde, 4-nitroacetophenone and 4-oxo-trans-2-nonenal (in vitro) (By similarity). (updated: Sept. 12, 2018)
Protein identification was indicated in the following studies:
- 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.
- 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
Hematopoietic progenitor cell differentiation
NADPH oxidation
Neuromuscular process
Neutrophil degranulation
Oxidation-reduction process
Potassium ion transmembrane transport
Regulation of action potential
Regulation of potassium ion transmembrane transport
Regulation of protein localization to cell surface
Cellular Component
Axon terminus
Cytoskeleton
Cytosol
Extrinsic component of cytoplasmic side of plasma membrane
Juxtaparanode region of axon
Membrane
Pinceau fiber
Plasma membrane
Postsynaptic density
Specific granule membrane
Synapse
Tertiary granule membrane
Voltage-gated potassium channel complex
The reference OMIM entry for this protein is 601142
Potassium channel, voltage-gated, shaker-related subfamily, beta member 2; kcnab2
Kcna2b
Kv-beta-2
DESCRIPTION
'Shaker' and other voltage-dependent potassium channel proteins help to determine the electrical properties of excitable cells and play additional physiologic roles in nonexcitable cell types. See KCNA1 (176260). Mammalian Shaker potassium channel alpha subunits associate with cytoplasmic beta subunits that modulate the inactivation of the channel. The beta subunits belong to a superfamily of NAD(P)H-dependent enzymes, suggesting that they may be involved in additional physiologic processes. Shaker potassium channel complexes are thought to be composed of 4 alpha and 4 beta subunits.CLONING
By PCR of a human hippocampal library with degenerate primers based on conserved regions of rat beta-1 (KCNA1B; 601141) and beta-2 subunits, McCormack et al. (1995) isolated cDNAs encoding human beta-1 and beta-2. The predicted 367-amino acid human, bovine, and rat beta-2 subunits are 99% identical. Unlike beta-1, the beta-2 subunit does not contain an N-terminal inactivation 'ball' domain. Instead, functional studies of beta-2 expressed in Xenopus oocytes indicated that it increased the rate of the endogenous Kv1.4 alpha subunit (176266) inactivation process.GENE STRUCTURE
Leicher et al. (1998) reported that the KCNA2B gene contains 15 exons and spans approximately 70 kb. The exon/intron structure of KCNA2B is comparable to that of KCNA1B and KCNA3B (604111), although the size of the introns varies significantly among the genes.MAPPING
By analysis of somatic cell hybrids and by FISH, Schultz et al. (1996) mapped the KCNA2B gene to 1p36.3.GENE FUNCTION
The results of Gong et al. (1999) suggested that ZIP, the rat homolog of p62 (601530), acts as a link that targets the activity of Kv-beta-2 and PKC-zeta (176982). Gu et al. (2003) found that Kv1 axonal targeting required its T1 tetramerization domain. When fused to unpolarized CD4 (186940) or dendritic transferrin receptor (TFR; 190010), Kv1 T1 domains promoted their axonal surface expression. Moreover, mutations in the T1 domain of Kv1.2 (176262) that eliminated association with Kv-beta-2 compromised axonal targeting, but not surface expression, of CD4-T1 fusion proteins. The authors concluded that proper association of Kv-beta with the Kv1 T1 domain is essential for axonal targeting.ANIMAL MODEL
McCormack et al. (2002) developed Kv-beta-2-null mice and mice carrying a tyr90-to-phe (Y90F) mutation in the putative aldo-keto reductase (103880)-like catalytic domain of Kv-beta-2. Null mice showed reduced life spans, occasional seizures, and cold swim-induced tremors, a phenotype similar to that observed in Kv1.1-null mice. In Kv-beta-2-null mice, Kv1.1 and Kv1.2 localized normally in cerebellar basket cell terminals and the juxtaparanodal region of myelinated nerves, suggesting that Kv-beta-2 does not have a chaperone-like function. Mice expressing the Y90F mutation had no overt phenotype. ... More on the omim web site
July 1, 2020: Protein entry updated
Automatic update: OMIM entry 601142 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).