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 site

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Feb. 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.