ADD2 explained

Beta-adducin is a protein that in humans is encoded by the ADD2 gene.^{[1] [2]}

Function

Adducins are heteromeric proteins composed of different subunits referred to as adducin alpha, beta, and gamma. The three subunits are 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.

While adducins alpha and gamma are ubiquitously expressed, the expression of adducin beta is restricted to brain and hematopoietic tissues. Adducin, originally purified from human erythrocytes, was found to be a heterodimer of adducins alpha and beta. Polymorphisms resulting in amino acid substitutions in these two subunits have been associated with the regulation of blood pressure in an animal model of hypertension. Heterodimers consisting of alpha and gamma subunits have also been described. Structurally, each subunit is composed 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. Various adducin beta mRNAs, alternatively spliced at 3' end and/or internally spliced and encoding different isoforms, have been described. The functions of all the different isoforms are not known.

Interactions

ADD2 has been shown to interact with FYN.^[3]

Further reading

• Gilligan DM, Lieman J, Bennett V . Assignment of the human beta-adducin gene (ADD2) to 2p13-p14 by in situ hybridization . Genomics . 28 . 3 . 610–2 . 1996 . 7490111 . 10.1006/geno.1995.1205 . free .
• Hughes CA, Bennett V . Adducin: a physical model with implications for function in assembly of spectrin-actin complexes . J. Biol. Chem. . 270 . 32 . 18990–6 . 1995 . 7642559 . 10.1074/jbc.270.32.18990 . free .
• Miyazaki M, Kaibuchi K, Shirataki H . Rabphilin-3A binds to a M(r) 115,000 polypeptide in a phosphatidylserine- and Ca(2+)-dependent manner . Brain Res. Mol. Brain Res. . 28 . 1 . 29–36 . 1995 . 7707875 . 10.1016/0169-328X(94)00180-M . etal.
• Miyazaki M, Shirataki H, Kohno H . Identification as beta-adducin of a protein interacting with rabphilin-3A in the presence of Ca2+ and phosphatidylserine . Biochem. Biophys. Res. Commun. . 205 . 1 . 460–6 . 1995 . 7999065 . 10.1006/bbrc.1994.2688 . etal.
• White RA, Angeloni SV, Pasztor LM . Chromosomal localization of the beta-adducin gene to mouse chromosome 6 and human chromosome 2 . Mamm. Genome . 6 . 10 . 741–3 . 1996 . 8563174 . 10.1007/BF00354298 . 23628451 .
• Tisminetzky S, Devescovi G, Tripodi G . Genomic organisation and chromosomal localisation of the gene encoding human beta adducin . Gene . 167 . 1–2 . 313–6 . 1996 . 8566798 . 10.1016/0378-1119(95)00591-9 . etal.
• Matsuoka Y, Hughes CA, Bennett V . Adducin regulation. Definition of the calmodulin-binding domain and sites of phosphorylation by protein kinases A and C . J. Biol. Chem. . 271 . 41 . 25157–66 . 1996 . 8810272 . 10.1074/jbc.271.41.25157 . free .
• Gilligan DM, Lozovatsky L, Silberfein A . Organization of the human beta-adducin gene (ADD2) . Genomics . 43 . 2 . 141–8 . 1997 . 9244430 . 10.1006/geno.1997.4802 . free .
• Matsuoka Y, Li X, Bennett V . 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 . J. Cell Biol. . 142 . 2 . 485–97 . 1998 . 9679146 . 10.1083/jcb.142.2.485 . 2133059 .
• Gilligan DM, Lozovatsky L, Gwynn B . Targeted disruption of the β adducin gene (Add2) causes red blood cell spherocytosis in mice . Proc. Natl. Acad. Sci. U.S.A. . 96 . 19 . 10717–22 . 1999 . 10485892 . 10.1073/pnas.96.19.10717 . 17949 . 1999PNAS...9610717G . etal. free .
• Shima T, Okumura N, Takao T . Interaction of the SH2 domain of Fyn with a cytoskeletal protein, beta-adducin . J. Biol. Chem. . 276 . 45 . 42233–40 . 2001 . 11526103 . 10.1074/jbc.M102699200 . etal. free .
• Strausberg RL, Feingold EA, Grouse LH . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . etal. free .
• Citterio L, Tizzoni L, Catalano M . Expression analysis of the human adducin gene family and evidence of ADD2 beta4 multiple splicing variants . Biochem. Biophys. Res. Commun. . 309 . 2 . 359–67 . 2003 . 12951058 . 10.1016/j.bbrc.2003.08.011 . etal.
• Tikhonoff V, Kuznetsova T, Stolarz K . beta-Adducin polymorphisms, blood pressure, and sodium excretion in three European populations . Am. J. Hypertens. . 16 . 10 . 840–6 . 2004 . 14553963 . 10.1016/S0895-7061(03)00975-0 . etal. free .
• Brandenberger R, Wei H, Zhang S . Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation . Nat. Biotechnol. . 22 . 6 . 707–16 . 2005 . 15146197 . 10.1038/nbt971 . 27764390 . etal.
• Ballif BA, Villén J, Beausoleil SA . Phosphoproteomic analysis of the developing mouse brain . Mol. Cell. Proteomics . 3 . 11 . 1093–101 . 2005 . 15345747 . 10.1074/mcp.M400085-MCP200 . etal. free .
• Gerhard DS, Wagner L, Feingold EA . The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . etal.
• Efendiev R, Krmar RT, Ogimoto G . Hypertension-linked mutation in the adducin alpha-subunit leads to higher AP2-mu2 phosphorylation and impaired Na+,K+-ATPase trafficking in response to GPCR signals and intracellular sodium . Circ. Res. . 95 . 11 . 1100–8 . 2005 . 15528469 . 10.1161/01.RES.0000149570.20845.89 . etal. free .
• Lanzani C, Citterio L, Jankaricova M . Role of the adducin family genes in human essential hypertension . J. Hypertens. . 23 . 3 . 543–9 . 2005 . 15716695 . 10.1097/01.hjh.0000160210.48479.78 . 37253591 . etal.

Notes and References

1. Joshi R, Gilligan DM, Otto E, McLaughlin T, Bennett V . Primary structure and domain organization of human alpha and beta adducin . J Cell Biol . 115 . 3 . 665–75 . Nov 1991. 1840603 . 2289184 . 10.1083/jcb.115.3.665 .
2. Web site: Entrez Gene: ADD2 adducin 2 (beta).
3. Shima T, Okumura N, Takao T, Satomi Y, Yagi T, Okada M, Nagai K . Interaction of the SH2 domain of Fyn with a cytoskeletal protein, beta-adducin . J. Biol. Chem. . 276 . 45 . 42233–40 . November 2001 . 11526103 . 10.1074/jbc.M102699200 . free .