ADD3 (adducin 3)

2005-03-01   José Luis Vizmanos 

Departamento de Genética, Facultad de Ciencias, Universidad de Navarra, 31008 Pamplona, Navarra, Espana

Identity

HGNC
LOCATION
10q25.1
IMAGE
Atlas Image
LEGEND
Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics
LOCUSID
ALIAS
ADDL,CPSQ3
FUSION GENES

DNA/RNA

Atlas Image
Genomic structure of ADD3. Black boxes indicate exons.

Description

15 exons spanning 129.52 Kb on 10q25.1-10q25.2. Transcription is from centromere to telomere.

Transcription

2 alternative transcripts :
  • Variant 1 includes an in-frame alternate coding exon and encodes a longer protein isoform (isoform a) compared to transcript variant 2.
  • Variant 2 lacks an in-frame alternate coding exon and exon 13 and encodes a shorter protein (isoform b) compared to transcript variant 1.
    3 alternative transcripts corresponding to variant 1 and 2.
  • Proteins

    Note

    adducin 3 (adducin-like)
    Atlas Image
    Schematic representation of ADD3. AldolaseII-N: domain belonging to aldolase class I family, adducin subfamily N-terminal, Coils: coiled-coil domain, Bipartite NLS: Bipartite nuclear localization signal.

    Description

    is membrane-cytoskeleton-associated protein that promotes the assembly of the spectrin-actin network and binds to calmodulin.
    Adducins are heteromeric proteins composed of different subunits referred to as adducin alpha, beta and gamma encoded by distinct genes and belong to a family of membrane skeletal proteins involved in the assembly of spectrin-actin network in erythrocytes and at sites of cell-cell contact in epithelial tissues. Structurally, each subunit is comprised of two distinct domains. The amino-terminal region is protease resistant and globular in shape, while the carboxy-terminal region is protease sensitive. The latter contains multiple phosphorylation sites for protein kinase C, the binding site for calmodulin, and is required for association with spectrin and actin. Alternatively spliced adducin gamma transcripts encoding different isoforms have been described. The functions of the different isoforms are not known.

    Expression

    Ubiquitous. Heart only expresses isoform 1 or a.

    Localisation

    Membrane skeleton.

    Function

    Adducins are membrane skeletal proteins involved in the assembly of spectrin-actin network in erythrocytes and at sites of cell-cell contact in epithelial tissues. Adducin is a heterodimeric cytoskeleton protein and consists of an [alpha]-subunit (Mr 103 kDa) and either a [beta]- (Mr 97 kDa) or [gamma]-subunit (Mr 90kDa). Three genes (ADD1, ADD2, and ADD3, respectively) that map to different chromosomes encode these subunits. Adducin promotes the organization of the spectrin-actin lattice by favoring the spectrin-actin binding and controlling the rate of actin polymerization as an end-capping actin protein. Its function is calcium- and calmodulin-dependent. It is phosphorylated by protein kinases A and C, tyrosine, and [rho]-kinases.10 It is a member of the myristoylated alanine-rich C kinase substrate protein family, which is involved in signal transduction, cell-to-cell contact formation, and cell migration. Non-silent polymorphisms resulting in subunits alpha and beta have been associated with the regulation of blood pressure in an animal model of hypertension.

    Homology

    It presents homology in various species. It also belongs to ADDUCIN protein family (3 members ADD1, ADD2 and ADD3).

    Mutations

    Germinal

    It has been shown that the interaction of ADD1 and ADD3 gene variants in humans is statistically associated with variation in blood pressure, suggesting the presence of epistatic effects among these loci.

    Somatic

    t(10;11)(q25;p15) 5 NUP98-ADD3 3 fusion in a T-cell acute lymphoblastic leukemia with biphenotipic characteristics (T/myeloid).

    Implicated in

    Entity name
    t(10;11)(q25;p15)
    Disease
    T-cell acute lymphoblastic leukemia with biphenotipic characteristics (T/myeloid)
    Prognosis
    bad
    Cytogenetics
    t(10;11)(q25;p15) (cryptic)
    Hybrid gene
    5 NUP98-ADD3 3
    Fusion protein
    NUP98-ADD3
    Atlas Image
    Schematic representation of the fusion NUP98-ADD3 consecuence of the t(10;11)(q25;p15) in a T-cell acute lymphoblastic leukemia with biphenotipic characteristics. From up to down: ADD3, NUP98 and the putative chimeric NUP98-ADD3 structure. FG-repeats, phenilalanine-glycine repeats; bipartite NLS, bipartite nuclear localization signal. Coiled coil domains on ADD3 and NUP98-ADD3 are indicated with asterisks.

    Bibliography

    Pubmed IDLast YearTitleAuthors
    156994492005Adducin polymorphism: detection and impact on hypertension and related disorders.Bianchi G et al
    105811741999Genomic organization of the human gamma adducin gene.Citterio L et al
    88938091996Cloning, expression and chromosome mapping of adducin-like 70 (ADDL), a human cDNA highly homologous to human erythrocyte adducin.Katagiri T et al
    86264791996A new function for adducin. Calcium/calmodulin-regulated capping of the barbed ends of actin filaments.Kuhlman PA et al
    128106322003NUP98 is fused to adducin 3 in a patient with T-cell acute lymphoblastic leukemia and myeloid markers, with a new translocation t(10;11)(q25;p15).Lahortiga I et al
    157166952005Role of the adducin family genes in human essential hypertension.Lanzani C et al
    109503042000Adducin: structure, function and regulation.Matsuoka Y et al
    123643922002Hypertension-linked decrease in the expression of brain gamma-adducin.Yang H et al
    147327362004Decrease in hypothalamic gamma adducin in rat models of hypertension.Yang H et al

    Other Information

    Locus ID:

    NCBI: 120
    MIM: 601568
    HGNC: 245
    Ensembl: ENSG00000148700

    Variants:

    dbSNP: 120
    ClinVar: 120
    TCGA: ENSG00000148700
    COSMIC: ADD3

    RNA/Proteins

    Gene IDTranscript IDUniprot
    ENSG00000148700ENST00000277900Q9UEY8
    ENSG00000148700ENST00000356080Q9UEY8
    ENSG00000148700ENST00000356080Q5VU08
    ENSG00000148700ENST00000360162Q9UEY8

    Expression (GTEx)

    0
    50
    100
    150
    200

    Pathways

    PathwaySourceExternal ID
    Transmembrane transport of small moleculesREACTOMER-HSA-382551
    Miscellaneous transport and binding eventsREACTOMER-HSA-5223345

    Protein levels (Protein atlas)

    Not detected
    Low
    Medium
    High

    References

    Pubmed IDYearTitleCitations
    199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
    163854512006A scan of chromosome 10 identifies a novel locus showing strong association with late-onset Alzheimer disease.69
    203796142010Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.62
    208107862010Adducins regulate remodeling of apical junctions in human epithelial cells.42
    238142652013MiR-145 functions as a tumor-suppressive RNA by targeting Sox9 and adducin 3 in human glioma cells.41
    241045242014Replication of a GWAS signal in a Caucasian population implicates ADD3 in susceptibility to biliary atresia.23
    238726022013Common genetic variants regulating ADD3 gene expression alter biliary atresia risk.21
    157166952005Role of the adducin family genes in human essential hypertension.15
    157166952005Role of the adducin family genes in human essential hypertension.15
    238365062013Mutations in γ adducin are associated with inherited cerebral palsy.14

    Citation

    José Luis Vizmanos

    ADD3 (adducin 3)

    Atlas Genet Cytogenet Oncol Haematol. 2005-03-01

    Online version: http://atlasgeneticsoncology.org/gene/520/add3