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ADD3 (adducin 3)

Identity

Other namesADDL
Adducin-like
adducin 3 (gamma)
gamma adducin (adducin-like protein 70)
HGNC ADD3
Location 10q25.1-q25.2
Location_base_pair Starts at 111757701 and ends at 111885313 bp from pter ( according to hg18-Mar_2006).
Local_order MXI1 (MAX-interacting protein 1) is more telomeric. XPNPEP1 (X-prolylaminopeptidase 1) is more telomeric.

DNA/RNA

 
  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.
  • Protein

    Note adducin 3 (adducin-like)
     
      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 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/Mutated Gene 5' NUP98-ADD3 3'
    Abnormal Protein NUP98-ADD3
     
    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.
      

    External links

    Nomenclature
    HGNCADD3   245
    Entrez_GeneADD3  120  adducin 3 (gamma)
    Cards
    AtlasADD3ID520ch10q25
    GeneCardsADD3
    EnsemblADD3 [Search_View]   ENSG00000148700 [Gene_View]  ADD3 [Vega]
    GenatlasADD3
    GeneLynxADD3
    eGenomeADD3
    euGene120
    Genomic and cartography
    GoldenPathADD3  -     chr10:111757701-111885313 +  10q25.2   [Description]    (hg18-Mar_2006)
    EnsemblADD3 - 10q25.2 [CytoView]
    NCBIMapview
    OMIMDisease map [OMIM]
    HomoloGeneADD3
    Gene and transcription
    GenbankAB209810 [ ENTREZ ]
    GenbankAK130789 [ ENTREZ ]
    GenbankAK223270 [ ENTREZ ]
    GenbankAK291488 [ ENTREZ ]
    GenbankAL600737 [ ENTREZ ]
    RefSeqNM_001121 [ SRS ]    NM_001121 [ ENTREZ ]
    RefSeqNM_016824 [ SRS ]    NM_016824 [ ENTREZ ]
    RefSeqNM_019903 [ SRS ]    NM_019903 [ ENTREZ ]
    RefSeqAC_000053 [ SRS ]    AC_000053 [ ENTREZ ]
    RefSeqAC_000142 [ SRS ]    AC_000142 [ ENTREZ ]
    RefSeqNC_000010 [ SRS ]    NC_000010 [ ENTREZ ]
    RefSeqNT_030059 [ SRS ]    NT_030059 [ ENTREZ ]
    RefSeqNW_001838006 [ SRS ]    NW_001838006 [ ENTREZ ]
    RefSeqNW_924884 [ SRS ]    NW_924884 [ ENTREZ ]
    CCDSADD3 CCDS - NCBI
    AceViewADD3 AceView - NCBI
    UnigeneHs.501012 [ SRS ]    Hs.501012 [ NCBI ]     HS501012 [ spliceNest ]
    Fast-db16711 (alternative variants)
    Protein : pattern, domain, 3D structure
    HPRD03339
    Protein Interaction databases
    Polymorphism : SNP, mutations, diseases
    OMIM601568    [ map ]   
    GENECLINICS601568
    SNPADD3 [dbSNP-NCBI]  
    SNPNM_001121 [SNP-NCI]  
    SNPNM_016824 [SNP-NCI]  
    SNPNM_019903 [SNP-NCI]  
    SNPADD3 [GeneSNPs - Utah]  ADD3] [HGBASE - SRS]
    HAPMAPADD3 [HAPMAP]  
    TICdbADD3 [Translocation breakpoints In Cancer]  
    HGMDADD3
    Genetic AssociationADD3
    CDC HuGEADD3
    General knowledge
    Family BrowserADD3 [UCSC Family Browser]
    SOURCENM_001121
    SOURCENM_016824
    SOURCENM_019903
    SMDHs.501012
    SAGEHs.501012
    GOactin binding [Amigo]  actin binding
    GOstructural constituent of cytoskeleton [Amigo]  structural constituent of cytoskeleton
    GOcalmodulin binding [Amigo]  calmodulin binding
    GOcytoplasm [Amigo]  cytoplasm
    GOcytoskeleton [Amigo]  cytoskeleton
    GOplasma membrane [Amigo]  plasma membrane
    GOmetal ion binding [Amigo]  metal ion binding
    PubGeneADD3
    TreeFamADD3
    CTD120 [Comparative ToxicoGenomics Database]
    Other databases
    Probes
    ProbeADD3 Related clones (RZPD - Berlin)
    PubMed
    PubMed15 Pubmed reference(s) in Entrez

    Bibliography

    Cloning, expression and chromosome mapping of adducin-like 70 (ADDL), a human cDNA highly homologous to human erythrocyte adducin.
    Katagiri T, Ozaki K, Fujiwara T, Shimizu F, Kawai A, Okuno S, Suzuki M, Nakamura Y, Takahashi E, Hirai Y
    Cytogenetics and cell genetics. 1996 ; 74 (1-2) : 90-95.
    PMID 8893809
     
    A new function for adducin. Calcium/calmodulin-regulated capping of the barbed ends of actin filaments.
    Kuhlman PA, Hughes CA, Bennett V, Fowler VM
    The Journal of biological chemistry. 1996 ; 271 (14) : 7986-7991.
    PMID 8626479
     
    Genomic organization of the human gamma adducin gene.
    Citterio L, Azzani T, Duga S, Bianchi G
    Biochemical and biophysical research communications. 1999 ; 266 (1) : 110-114.
    PMID 10581174
     
    Adducin: structure, function and regulation.
    Matsuoka Y, Li X, Bennett V
    Cellular and molecular life sciences : CMLS. 2000 ; 57 (6) : 884-895.
    PMID 10950304
     
    Hypertension-linked decrease in the expression of brain gamma-adducin.
    Yang H, Francis SC, Sellers K, DeBarros M, Sun C, Sumners C, Ferrario CM, Katovich MJ, Muro AF, Raizada MK
    Circulation research. 2002 ; 91 (7) : 633-639.
    PMID 12364392
     
    NUP98 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, Vizmanos JL, Agirre X, Vˆ°zquez I, Cigudosa JC, Larrayoz MJ, Sala F, Gorosquieta A, Perez-Equiza K, Calasanz MJ, Odero MD
    Cancer research. 2003 ; 63 (12) : 3079-3083.
    PMID 12810632
     
    Decrease in hypothalamic gamma adducin in rat models of hypertension.
    Yang H, Reaves PY, Katovich MJ, Raizada MK
    Hypertension. 2004 ; 43 (2) : 324-328.
    PMID 14732736
     
    Adducin polymorphism: detection and impact on hypertension and related disorders.
    Bianchi G, Ferrari P, Staessen JA
    Hypertension. 2005 ; 45 (3) : 331-340.
    PMID 15699449
     
    Role of the adducin family genes in human essential hypertension.
    Lanzani C, Citterio L, Jankaricova M, Sciarrone MT, Barlassina C, Fattori S, Messaggio E, Serio CD, Zagato L, Cusi D, Hamlyn JM, Stella A, Bianchi G, Manunta P
    Journal of hypertension. 2005 ; 23 (3) : 543-549.
    PMID 15716695
     
    REVIEW articlesautomatic search in PubMed
    Last year publicationsautomatic search in PubMed

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    Contributor(s)

    Written03-2005José Luis Vizmanos

    Citation

    This paper should be referenced as such :
    Vizmanos JL . ADD3 (adducin 3). Atlas Genet Cytogenet Oncol Haematol. March 2005 .
    URL : http://AtlasGeneticsOncology.org/Genes/ADD3ID520ch10q25.html

    © Atlas of Genetics and Cytogenetics in Oncology and Haematology
    indexed on : Sun Nov 9 19:36:24 2008


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