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ADD3 (adducin 3)

Written2005-03José Luis Vizmanos
Departamento de Genética, Facultad de Ciencias, Universidad de Navarra, 31008 Pamplona, Navarra, Espana

(Note : for Links provided by Atlas : click)

Identity

Other namesADDL
Adducin-like
adducin 3 (gamma)
gamma adducin (adducin-like protein 70)
HGNC (Hugo) ADD3
LocusID (NCBI) 120
Atlas_Id 520
Location 10q25.1  [Link to chromosome band 10q25]
Location_base_pair Starts at 111767694 and ends at 111895323 bp from pter ( according to hg19-Feb_2009)  [Mapping ADD3.png]
Local_order MXI1 (MAX-interacting protein 1) is more telomeric. XPNPEP1 (X-prolylaminopeptidase 1) is more telomeric.
 
  Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics
Fusion genes
(updated 2016)
ADD3 (10q25.1) / MYT1L (2p25.3)ADD3 (10q25.1) / NUP98 (11p15.4)ADD3 (10q25.1) / OGT (Xq13.1)
ADD3 (10q25.1) / SYNPO2 (4q26)ADD3 (10q25.1) / XPNPEP1 (10q25.1)AMOTL2 (3q22.2) / ADD3 (10q25.1)
C1orf61 (1q22) / ADD3 (10q25.1)CLU (8p21.1) / ADD3 (10q25.1)FTL (19q13.33) / ADD3 (10q25.1)
NUP98 (11p15.4) / ADD3 (10q25.1)SCN2A (2q24.3) / ADD3 (10q25.1)

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

    Note
    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.
      

    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, Vázquez 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
     

    Citation

    This paper should be referenced as such :
    Vizmanos, JL
    ADD3 (adducin 3)
    Atlas Genet Cytogenet Oncol Haematol. 2005;9(2):129-131.
    Free journal version : [ pdf ]   [ DOI ]
    On line version : http://AtlasGeneticsOncology.org/Genes/ADD3ID520ch10q25.html


    Other Leukemias implicated (Data extracted from papers in the Atlas) [ 2 ]
      t(10;11)(q25;p15) NUP98/ADD3
    T-lineage acute lymphoblastic leukemia (T-ALL)

    External links

    Nomenclature
    HGNC (Hugo)ADD3   245
    Cards
    AtlasADD3ID520ch10q25
    Entrez_Gene (NCBI)ADD3  120  adducin 3
    AliasesADDL
    GeneCards (Weizmann)ADD3
    Ensembl hg19 (Hinxton)ENSG00000148700 [Gene_View]  chr10:111767694-111895323 [Contig_View]  ADD3 [Vega]
    Ensembl hg38 (Hinxton)ENSG00000148700 [Gene_View]  chr10:111767694-111895323 [Contig_View]  ADD3 [Vega]
    ICGC DataPortalENSG00000148700
    TCGA cBioPortalADD3
    AceView (NCBI)ADD3
    Genatlas (Paris)ADD3
    WikiGenes120
    SOURCE (Princeton)ADD3
    Genomic and cartography
    GoldenPath hg19 (UCSC)ADD3  -     chr10:111767694-111895323 +  10q25.2   [Description]    (hg19-Feb_2009)
    GoldenPath hg38 (UCSC)ADD3  -     10q25.2   [Description]    (hg38-Dec_2013)
    EnsemblADD3 - 10q25.2 [CytoView hg19]  ADD3 - 10q25.2 [CytoView hg38]
    Mapping of homologs : NCBIADD3 [Mapview hg19]  ADD3 [Mapview hg38]
    OMIM601568   
    Gene and transcription
    Genbank (Entrez)AB209810 AK130789 AK223270 AK291488 AL600737
    RefSeq transcript (Entrez)NM_001121 NM_001320591 NM_001320592 NM_001320593 NM_001320594 NM_016824 NM_019903
    RefSeq genomic (Entrez)NC_000010 NC_018921 NT_030059 NW_004929376
    Consensus coding sequences : CCDS (NCBI)ADD3
    Cluster EST : UnigeneHs.501012 [ NCBI ]
    CGAP (NCI)Hs.501012
    Alternative Splicing GalleryENSG00000148700
    Gene ExpressionADD3 [ NCBI-GEO ]   ADD3 [ EBI - ARRAY_EXPRESS ]   ADD3 [ SEEK ]   ADD3 [ MEM ]
    Gene Expression Viewer (FireBrowse)ADD3 [ Firebrowse - Broad ]
    SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
    GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
    BioGPS (Tissue expression)120
    GTEX Portal (Tissue expression)ADD3
    Protein : pattern, domain, 3D structure
    UniProt/SwissProtQ9UEY8 (Uniprot)
    NextProtQ9UEY8  [Sequence]  [Exons]  [Medical]  [Publications]
    With graphics : InterProQ9UEY8
    Splice isoforms : SwissVarQ9UEY8 (Swissvar)
    PhosPhoSitePlusQ9UEY8
    Domains : Interpro (EBI)ADD3    Aldolase_II/adducin_N   
    Domain families : Pfam (Sanger)Aldolase_II (PF00596)   
    Domain families : Pfam (NCBI)pfam00596   
    Domain families : Smart (EMBL)Aldolase_II (SM01007)  
    DMDM Disease mutations120
    Blocks (Seattle)ADD3
    SuperfamilyQ9UEY8
    Human Protein AtlasENSG00000148700
    Peptide AtlasQ9UEY8
    HPRD03339
    IPIIPI00004408   IPI00220754   IPI00978183   
    Protein Interaction databases
    DIP (DOE-UCLA)Q9UEY8
    IntAct (EBI)Q9UEY8
    FunCoupENSG00000148700
    BioGRIDADD3
    STRING (EMBL)ADD3
    ZODIACADD3
    Ontologies - Pathways
    QuickGOQ9UEY8
    Ontology : AmiGOcondensed nuclear chromosome  actin binding  protein kinase C binding  structural constituent of cytoskeleton  calmodulin binding  nucleoplasm  cytoplasm  cytosol  cytoskeleton  plasma membrane  brush border  cell-cell junction  cell cortex  membrane  response to drug  transmembrane transport  neuronal postsynaptic density  
    Ontology : EGO-EBIcondensed nuclear chromosome  actin binding  protein kinase C binding  structural constituent of cytoskeleton  calmodulin binding  nucleoplasm  cytoplasm  cytosol  cytoskeleton  plasma membrane  brush border  cell-cell junction  cell cortex  membrane  response to drug  transmembrane transport  neuronal postsynaptic density  
    REACTOMEQ9UEY8 [protein]
    REACTOME PathwaysR-HSA-5223345 Miscellaneous transport and binding events [pathway]
    NDEx Network
    Atlas of Cancer Signalling NetworkADD3
    Wikipedia pathwaysADD3
    Orthology - Evolution
    OrthoDB120
    GeneTree (enSembl)ENSG00000148700
    Phylogenetic Trees/Animal Genes : TreeFamADD3
    Homologs : HomoloGeneADD3
    Homology/Alignments : Family Browser (UCSC)ADD3
    Gene fusions - Rearrangements
    Fusion : MitelmanADD3/OGT [10q25.1/Xq13.1]  
    Fusion : MitelmanADD3/XPNPEP1 [10q25.1/10q25.1]  [t(10;10)(q25;q25)]  
    Fusion : MitelmanFTL/ADD3 [19q13.33/10q25.1]  [t(10;19)(q25;q13)]  
    Fusion : MitelmanNUP98/ADD3 [11p15.4/10q25.1]  [t(10;11)(q25;p15)]  
    Fusion: TCGAADD3 10q25.1 OGT Xq13.1 LGG
    Fusion: TCGAADD3 10q25.1 XPNPEP1 10q25.1 BRCA
    Fusion : TICdbNUP98 [11p15.4]  -  ADD3 [10q25.1]
    Polymorphisms : SNP, variants
    NCBI Variation ViewerADD3 [hg38]
    dbSNP Single Nucleotide Polymorphism (NCBI)ADD3
    dbVarADD3
    ClinVarADD3
    1000_GenomesADD3 
    Exome Variant ServerADD3
    ExAC (Exome Aggregation Consortium)ADD3 (select the gene name)
    Genetic variants : HAPMAP120
    Genomic Variants (DGV)ADD3 [DGVbeta]
    Mutations
    ICGC Data PortalADD3 
    TCGA Data PortalADD3 
    Broad Tumor PortalADD3
    OASIS PortalADD3 [ Somatic mutations - Copy number]
    Somatic Mutations in Cancer : COSMICADD3 
    LOVD (Leiden Open Variation Database)Whole genome datasets
    LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
    LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
    BioMutasearch ADD3
    DgiDB (Drug Gene Interaction Database)ADD3
    DoCM (Curated mutations)ADD3 (select the gene name)
    CIViC (Clinical Interpretations of Variants in Cancer)ADD3 (select a term)
    intoGenADD3
    Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
    Diseases
    DECIPHER (Syndromes)10:111767694-111895323  ENSG00000148700
    CONAN: Copy Number AnalysisADD3 
    Mutations and Diseases : HGMDADD3
    OMIM601568   
    MedgenADD3
    Genetic Testing Registry ADD3
    NextProtQ9UEY8 [Medical]
    TSGene120
    GENETestsADD3
    Huge Navigator ADD3 [HugePedia]
    snp3D : Map Gene to Disease120
    BioCentury BCIQADD3
    ClinGenADD3
    Clinical trials, drugs, therapy
    Chemical/Protein Interactions : CTD120
    Chemical/Pharm GKB GenePA24567
    Clinical trialADD3
    Miscellaneous
    canSAR (ICR)ADD3 (select the gene name)
    Probes
    Litterature
    PubMed40 Pubmed reference(s) in Entrez
    GeneRIFsGene References Into Functions (Entrez)
    CoreMineADD3
    EVEXADD3
    GoPubMedADD3
    iHOPADD3
    REVIEW articlesautomatic search in PubMed
    Last year publicationsautomatic search in PubMed

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    indexed on : Sat Jun 11 12:58:17 CEST 2016

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