Beta-adducin (ADD2)
The protein contains 726 amino acids for an estimated molecular weight of 80854 Da.
Membrane-cytoskeleton-associated protein that promotes the assembly of the spectrin-actin network. Binds to the erythrocyte membrane receptor SLC2A1/GLUT1 and may therefore provide a link between the spectrin cytoskeleton to the plasma membrane. Binds to calmodulin. Calmodulin binds preferentially to the beta subunit. (updated: March 4, 2015)
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.
- 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.
- 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.
- 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.
| 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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| Variant | Description |
|---|---|
| dbSNP:rs4986 | |
| dbSNP:rs4987 | |
| dbSNP:rs4982 | |
| dbSNP:rs17855969 | |
| dbSNP:rs4985 |
Biological Process
Actin cytoskeleton organization
Actin filament bundle assembly
Barbed-end actin filament capping
Hemopoiesis
Leukocyte migration
Leukocyte tethering or rolling
Positive regulation of protein binding
Protein complex assembly
Protein-containing complex assembly
Synapse assembly
Transmembrane transport
The reference OMIM entry for this protein is 102681
Adducin 2; add2
Adducin, beta
DESCRIPTION
Adducin is a heterodimeric calmodulin (114180)-binding protein of the cell-membrane skeleton that is thought to play a role in assembly of the spectrin-actin (182860/102560) lattice that underlies the plasma membrane (Joshi et al., 1991).CLONING
Joshi et al. (1991) determined the sequence of cDNAs encoding the human alpha- (ADD1; 102680) and beta-adducins. The 726-amino acid predicted beta subunit is 49% identical to the alpha-adducin sequence. Gilligan et al. (1997) described 5 ADD2 splice variants that differed predominantly in the splicing of 3-prime exons. Some isoforms encoded by these variants lack the central calmodulin-binding domain or the lysine-rich C-terminal domain of the full-length protein. In a comprehensive assay of gene expression, Gilligan et al. (1999) showed ubiquitous expression of alpha- and gamma-adducin (ADD3; 601568), in contrast with the restricted expression of beta-adducin. Beta-adducin was expressed at high levels in brain and hematopoietic tissues (bone marrow in humans, and spleen in mice).GENE STRUCTURE
Tisminetzky et al. (1995) determined the genomic organization of the human beta-adducin gene and showed that it contains 13 exons spanning approximately 50 kb. The authors showed that alternative splicing results in the production of several different transcripts. Gilligan et al. (1997) determined that the ADD2 gene contains 17 exons and spans over 100 kb. The first 2 exons are noncoding, and coding exons 3 through 6 are common to all splice variants. The promoter region lacks TATA or CAAT elements, but is GC-rich and contains several binding sites for transcription factors.GENE FUNCTION
Ruediger et al. (2011) investigated how mossy fiber terminal complexes at the entry of hippocampal and cerebellar circuits rearrange upon learning in mice, and the functional role of the rearrangements. Ruediger et al. (2011) showed that one-trial and incremental learning lead to robust, circuit-specific, long-lasting, and reversible increases in the numbers of filopodial synapses onto fast-spiking interneurons that trigger feedforward inhibition. The increase in feedforward inhibition connectivity involved a majority of the presynaptic terminals, restricted the number of c-Fos (164810)-expressing postsynaptic neurons at memory retrieval, and correlated temporally with the quality of the memory. Ruediger et al. (2011) then showed that for contextual fear conditioning and Morris water maze learning, increased feedforward inhibition connectivity by hippocampal mossy fibers has a critical role for the precision of the memory and the learned behavior. In the absence of mossy fiber long-term potentiation in Rab3a (179490)-null mice, c-Fos ensemble reorganization and feedforward inhibition growth were both absent in CA3 upon learning, and the memory was imprecise. By contrast, in the absence of Add2, c-Fos reorganization was normal, but feedforward inhibition growth was abolished. In parallel, c-Fos ensembles in CA3 were greatly enlarged, and the memory was imprecise. Feedforward inhibition growth and memory precision were both rescued by re-expression of Add2 specifically in hippocampal mossy fibers. Ruediger et al. (2011) concluded that their results established a causal relationship between learning-related increases in the numbers of defined synapses and the precision of learning and memory in the adult. The results further related plasticity and feedforward inhibit ... More on the omim web siteFeb. 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 16, 2016: Protein entry updated
Automatic update: OMIM entry 102681 was added.