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Gene Review

ADD1  -  adducin 1 (alpha)

Homo sapiens

Synonyms: ADDA, Alpha-adducin, Erythrocyte adducin subunit alpha
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Disease relevance of ADD1


Psychiatry related information on ADD1


High impact information on ADD1

  • Cloning of the alpha-adducin gene from the Huntington's disease candidate region of chromosome 4 by exon amplification [7].
  • Exons recovered from cosmid Y24 identified cDNA clones corresponding to the alpha-subunit of adducin, a calmodulin-binding protein that is thought to promote assembly of spectrin-actin complexes in the formation of the membrane cytoskeleton, alpha-adducin is widely expressed and, at least in brain, is encoded by alternatively spliced mRNAs [7].
  • CONTEXT: A genetic variant in alpha-adducin has been associated with renal sodium reabsorption and salt-sensitive hypertension [8].
  • The blood-pressure response to acute and chronic changes in sodium balance was studied in hypertensive individuals with and without the 460 Trp alpha-adducin allele [9].
  • We investigated whether an alpha-adducin polymorphism (Gly 460 Trp) is involved in essential hypertension in two separate populations [9].

Chemical compound and disease context of ADD1


Biological context of ADD1

  • Adducin is a heterodimeric cytoskeleton protein, the three subunits of which are encoded by genes (ADD1, ADD2, and ADD3) that map to three different chromosomes [14].
  • CONCLUSIONS: 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 [1].
  • However, the differences in SBP and DBP between the two ADD1 genotypes were greatest in carriers of the ADD3 G allele (around + 8 mmHg) [1].
  • The mouse Lipe promoter region contains numerous potential binding motifs for factors implicated in adipose tissue expression and hormone responsiveness including adipocyte determination- and differentiation-dependent factor 1 (ADD1/SREBP1) [15].
  • Examples of this regulation, during adipogenesis, is the transactivation of the PPARgamma promoter by transcription factors of the classical pathway, such as C/EBPs or ADD1/SREBP1, but also newly identified factors, such as E2Fs [16].

Anatomical context of ADD1


Associations of ADD1 with chemical compounds


Regulatory relationships of ADD1


Other interactions of ADD1


Analytical, diagnostic and therapeutic context of ADD1

  • ADD1 G460W was associated with insulin sensitivity only after adjusting for body mass index [29].
  • Co-immunoprecipitation studies using in vitro-translated proteins demonstrated further the physical interaction of Id and ADD1/SREBP-1c proteins in the absence of DNA [30].
  • Sequences within this 69-bp DNA, including the SRE-1 cis-acting element, show strong binding to the purified nuclear transcription factor ADD1 (Tonzonoz, P., Kim, J. B., Graves, R. A., and Spiegelman B. M. (1993) Mol. Cell Biol. 13, 4753-4759) by mobility shift assay and footprinting analyses [31].
  • The results of this population-based cohort study suggest that the ADD1 gene contributes to the risk of hypertension and increases mean common carotid IMT in patients with type 2 diabetes [32].
  • Genotypes for ADD1 were detected by automated genomic polymerase chain reaction (PCR) [33].


  1. Role of the adducin family genes in human essential hypertension. Lanzani, C., Citterio, L., Jankaricova, M., Sciarrone, M.T., Barlassina, C., Fattori, S., Messaggio, E., Serio, C.D., Zagato, L., Cusi, D., Hamlyn, J.M., Stella, A., Bianchi, G., Manunta, P. J. Hypertens. (2005) [Pubmed]
  2. Weight loss reduces expression of SREBP1c/ADD1 and PPARgamma2 in adipose tissue of obese women. Ribot, J., Rantala, M., Kesäniemi, Y.A., Palou, A., Savolainen, M.J. Pflugers Arch. (2001) [Pubmed]
  3. Adducin polymorphism: detection and impact on hypertension and related disorders. Bianchi, G., Ferrari, P., Staessen, J.A. Hypertension (2005) [Pubmed]
  4. Blood pressure in patients with primary aldosteronism is influenced by bradykinin B(2) receptor and alpha-adducin gene polymorphisms. Mulatero, P., Williams, T.A., Milan, A., Paglieri, C., Rabbia, F., Fallo, F., Veglio, F. J. Clin. Endocrinol. Metab. (2002) [Pubmed]
  5. Primary structure and domain organization of human alpha and beta adducin. Joshi, R., Gilligan, D.M., Otto, E., McLaughlin, T., Bennett, V. J. Cell Biol. (1991) [Pubmed]
  6. A gene from chromosome 4p16.3 with similarity to a superfamily of transporter proteins. Duyao, M.P., Taylor, S.A., Buckler, A.J., Ambrose, C.M., Lin, C., Groot, N., Church, D., Barnes, G., Wasmuth, J.J., Housman, D.E. Hum. Mol. Genet. (1993) [Pubmed]
  7. Cloning of the alpha-adducin gene from the Huntington's disease candidate region of chromosome 4 by exon amplification. Taylor, S.A., Snell, R.G., Buckler, A., Ambrose, C., Duyao, M., Church, D., Lin, C.S., Altherr, M., Bates, G.P., Groot, N. Nat. Genet. (1992) [Pubmed]
  8. Diuretic therapy, the alpha-adducin gene variant, and the risk of myocardial infarction or stroke in persons with treated hypertension. Psaty, B.M., Smith, N.L., Heckbert, S.R., Vos, H.L., Lemaitre, R.N., Reiner, A.P., Siscovick, D.S., Bis, J., Lumley, T., Longstreth, W.T., Rosendaal, F.R. JAMA (2002) [Pubmed]
  9. Polymorphisms of alpha-adducin and salt sensitivity in patients with essential hypertension. Cusi, D., Barlassina, C., Azzani, T., Casari, G., Citterio, L., Devoto, M., Glorioso, N., Lanzani, C., Manunta, P., Righetti, M., Rivera, R., Stella, P., Troffa, C., Zagato, L., Bianchi, G. Lancet (1997) [Pubmed]
  10. Carotid and femoral intima-media thickness in relation to three candidate genes in a Caucasian population. Balkestein, E.J., Wang, J.G., Struijker-Boudier, H.A., Barlassina, C., Bianchi, G., Birkenhäger, W.H., Brand, E., Den Hond, E., Fagard, R., Herrmann, S.M., Van Bortel, L.M., Staessen, J.A. J. Hypertens. (2002) [Pubmed]
  11. Progesterone stimulates adipocyte determination and differentiation 1/sterol regulatory element-binding protein 1c gene expression. potential mechanism for the lipogenic effect of progesterone in adipose tissue. Lacasa, D., Le Liepvre, X., Ferre, P., Dugail, I. J. Biol. Chem. (2001) [Pubmed]
  12. Genetic polymorphisms and spontaneous preterm birth. Gibson, C.S., MacLennan, A.H., Dekker, G.A., Goldwater, P.N., Dambrosia, J.M., Munroe, D.J., Tsang, S., Stewart, C., Nelson, K.B. Obstetrics and gynecology (2007) [Pubmed]
  13. Lack of evidence for an association between alpha-adducin and blood pressure regulation in Asian populations. Ranade, K., Hsuing, A.C., Wu, K.D., Chang, M.S., Chen, Y.T., Hebert, J., Chen, Y.I., Olshen, R., Curb, D., Dzau, V., Botstein, D., Cox, D., Risch, N. Am. J. Hypertens. (2000) [Pubmed]
  14. Pharmacogenomics and pharmacogenetics of hypertension: update and perspectives--the adducin paradigm. Manunta, P., Bianchi, G. J. Am. Soc. Nephrol. (2006) [Pubmed]
  15. Hormone-sensitive lipase (Lipe): sequence analysis of the 129Sv mouse Lipe gene. Sztrolovics, R., Wang, S.P., Lapierre, P., Chen, H.S., Robert, M.F., Mitchell, G.A. Mamm. Genome (1997) [Pubmed]
  16. Atypical transcriptional regulators and cofactors of PPARgamma. Miard, S., Fajas, L. International journal of obesity (2005) (2005) [Pubmed]
  17. Induction of adipocyte-like phenotype in human mesenchymal stem cells by hypoxia. Fink, T., Abildtrup, L., Fogd, K., Abdallah, B.M., Kassem, M., Ebbesen, P., Zachar, V. Stem Cells (2004) [Pubmed]
  18. Expression analysis of the human adducin gene family and evidence of ADD2 beta4 multiple splicing variants. Citterio, L., Tizzoni, L., Catalano, M., Zerbini, G., Bianchi, G., Barlassina, C. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  19. Cleavage of the actin-capping protein alpha -adducin at Asp-Asp-Ser-Asp633-Ala by caspase-3 is preceded by its phosphorylation on serine 726 in cisplatin-induced apoptosis of renal epithelial cells. van de Water, B., Tijdens, I.B., Verbrugge, A., Huigsloot, M., Dihal, A.A., Stevens, J.L., Jaken, S., Mulder, G.J. J. Biol. Chem. (2000) [Pubmed]
  20. Adducin is an in vivo substrate for protein kinase C: phosphorylation in the MARCKS-related domain inhibits activity in promoting spectrin-actin complexes and occurs in many cells, including dendritic spines of neurons. Matsuoka, Y., Li, X., Bennett, V. J. Cell Biol. (1998) [Pubmed]
  21. Hydrochlorothiazide efficacy and polymorphisms in ACE, ADD1 and GNB3 in healthy, male volunteers. Vormfelde, S.V., Sehrt, D., Bolte, D., Pahl, S., Tzvetkov, M., Brockmöller, J. Eur. J. Clin. Pharmacol. (2006) [Pubmed]
  22. Renal function in relation to three candidate genes in a Chinese population. Wang, J.G., Liu, L., Zagato, L., Xie, J., Fagard, R., Jin, K., Wang, J., Li, Y., Bianchi, G., Staessen, J.A., Liu, L. J. Mol. Med. (2004) [Pubmed]
  23. Rho-kinase induces association of adducin with the cytoskeleton in platelet activation. Tamaru, S., Fukuta, T., Kaibuchi, K., Matsuoka, Y., Shiku, H., Nishikawa, M. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  24. Multiple sequence elements are involved in the transcriptional regulation of the human squalene synthase gene. Guan, G., Dai, P.H., Osborne, T.F., Kim, J.B., Shechter, I. J. Biol. Chem. (1997) [Pubmed]
  25. RFX-1, a putative alpha Adducin interacting protein in a human kidney library. Boito, R., Menniti, M., Amato, R., Palmieri, C., Marinaro, C., Iuliano, R., Tripodi, G., Cusi, D., Fuiano, G., Perrotti, N. FEBS Lett. (2005) [Pubmed]
  26. PPAR gamma and the control of adipogenesis. Spiegelman, B.M., Hu, E., Kim, J.B., Brun, R. Biochimie (1997) [Pubmed]
  27. Association between hypertension and the alpha-adducin, beta1-adrenoreceptor, and G-protein beta3 subunit genes in the Japanese population; the Suita study. Shioji, K., Kokubo, Y., Mannami, T., Inamoto, N., Morisaki, H., Mino, Y., Tagoi, N., Yasui, N., Iwaii, N. Hypertens. Res. (2004) [Pubmed]
  28. Salt sensitivity of Japanese from the viewpoint of gene polymorphism. Katsuya, T., Ishikawa, K., Sugimoto, K., Rakugi, H., Ogihara, T. Hypertens. Res. (2003) [Pubmed]
  29. Hypertension genes are genetic markers for insulin sensitivity and resistance. Guo, X., Cheng, S., Taylor, K.D., Cui, J., Hughes, R., Quiñones, M.J., Bulnes-Enriquez, I., De la Rosa, R., Aurea, G., Yang, H., Hsueh, W., Rotter, J.I. Hypertension (2005) [Pubmed]
  30. Functional antagonism between inhibitor of DNA binding (Id) and adipocyte determination and differentiation factor 1/sterol regulatory element-binding protein-1c (ADD1/SREBP-1c) trans-factors for the regulation of fatty acid synthase promoter in adipocytes. Moldes, M., Boizard, M., Liepvre, X.L., Fève, B., Dugail, I., Pairault, J. Biochem. J. (1999) [Pubmed]
  31. Molecular cloning and functional analysis of the promoter of the human squalene synthase gene. Guan, G., Jiang, G., Koch, R.L., Shechter, I. J. Biol. Chem. (1995) [Pubmed]
  32. The {alpha}-Adducin Gene Is Associated With Macrovascular Complications and Mortality in Patients With Type 2 Diabetes. Yazdanpanah, M., Sayed-Tabatabaei, F.A., Hofman, A., Aulchenko, Y.S., Oostra, B.A., Stricker, B.H., Pols, H.A., Lamberts, S.W., Witteman, J.C., Janssen, J.A., van Duijn, C.M. Diabetes (2006) [Pubmed]
  33. The 460Trp allele of alpha-adducin increases carotid intima-media thickness in young adult males. Sarzani, R., Cusi, D., Salvi, F., Barlassina, C., Macciardi, F., Pietrucci, F., Cola, G., Catalini, R., Dal Fiume, C., Dessì-Fulgheri, P., Rappelli, A. J. Hypertens. (2006) [Pubmed]
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