Gamma-adducin (ADD3)
The protein contains 706 amino acids for an estimated molecular weight of 79155 Da.
Membrane-cytoskeleton-associated protein that promotes the assembly of the spectrin-actin network. Plays a role in actin filament capping (PubMed:23836506). Binds to calmodulin. (updated: Nov. 22, 2017)
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 |
|---|---|
| CPSQ3 |
No binding partner found
Biological Process
Actin filament bundle assembly
Barbed-end actin filament capping
Transmembrane transport
The reference OMIM entry for this protein is 601568
Adducin 3; add3
Adducin, gamma
Adducin-like; addl add3/nup98 fusion gene, included
CLONING
From a human fetal-brain cDNA library, Katagiri et al. (1996) isolated a novel human cDNA which they termed adducin-like 70. The predicted amino acid sequence shows a high degree of homology to adducins alpha (102680) and beta (102681). In human erythrocytes, adducin is a 200-kD heterodimeric skeletal component of the cell membrane, where it promotes the binding of spectrin to actin. This binding is regulated by calcium/calmodulin (114180). Adducin also is phosphorylated by protein kinase C. Adducin and its multiple isoforms represent a family of proteins present in a variety of tissues and cultured cell lines, including those from brain, kidney, and liver. The gene, symbolized here ADDL, contains an open reading frame of 2,022 nucleotides encoding 674 amino acids. It shows 54%, 53%, and 59% identity in predicted amino acid sequence with alpha and beta components of human adducin and rat adducin 63, respectively. Katagiri et al. (1996) stated that human adducin-like 70 is likely to play an important role in the skeletal organization of the cell membrane. Northern blot analysis indicated ubiquitous expression of this gene in adult human tissues. In a comprehensive assay of gene expression, Gilligan et al. (1999) showed the ubiquitous expression of alpha- and gamma-adducin, in contrast to the restricted expression of beta-adducin. Beta-adducin was expressed at high levels in brain and hematopoietic tissues (bone marrow in humans, spleen in mice). By RT-PCR of peripheral blood leukocyte RNA, Citterio et al. (1999) identified a splice variant of ADD3 that includes exon 13. The deduced 706-amino acid protein contains 32 additional amino acids in its C-terminal tail compared with the protein described by Katagiri et al. (1996). RT-PCR detected both splice variants in kidney, brain, lung, and heart.GENE STRUCTURE
Citterio et al. (1999) determined that the ADD3 gene contains 14 coding exons and spans over 20 kb.MAPPING
Katagiri et al. (1996) localized the gene to chromosome 10q24.2-q24.3 by fluorescence in situ hybridization. By radiation hybrid analysis, Citterio et al. (1999) mapped the ADD3 gene to chromosome 10q24.1-q24.2.MOLECULAR GENETICS
Lanzani et al. (2005) analyzed the ADD3 gene in 40 unrelated individuals and identified a +386A-G polymorphism (dbSNP rs3731366) in intron 11. The authors then genotyped 512 newly discovered and never-treated hypertensive patients (see 145500) for IVS11+386A-G, but found no association between the polymorphism and ambulatory blood pressure or plasma levels of renin activity and endogenous ouabain. However, carriers of a 460W polymorphism in the ADD1 gene (102680.0001) who also carried the ADD3 G allele had an approximately 8 mm Hg greater increase in blood pressure than those who carried the ADD3 A allele (p = 0.020 to 0.006, depending on the genetic model applied). Lanzani et al. (2005) suggested that there were epistatic effects between the ADD1 and ADD3 loci affecting variation in blood pressure.CYTOGENETICS
- ADD3/NUP98 Fusion Gene Lahortiga et al. (2003) described a translocation t(10;11)(q25;p15) that resulted in fusion of the ADD3 gene to the NUP98 gene (601021) on chromosome 11p15 and development of T-cell acute lymphoblastic leukemia. ... More on the omim web siteFeb. 10, 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 16, 2016: Protein entry updated
Automatic update: OMIM entry 601568 was added.