ADD2

Adducin 2 (beta)
Identifiers
Symbols	ADD2 ; ADDB
External IDs	OMIM: 102681 MGI: 87919 HomoloGene: 1221 GeneCards: ADD2 Gene
Gene ontology Molecular function • actin binding • structural molecule activity • calmodulin binding • spectrin binding • protein homodimerization activity • protein heterodimerization activity • actin filament binding Cellular component • cytosol • plasma membrane • F-actin capping protein complex • cytoplasmic membrane-bounded vesicle • neuronal postsynaptic density Biological process • protein complex assembly • ion transport • actin cytoskeleton organization • hemopoiesis • positive regulation of protein binding • barbed-end actin filament capping • actin filament bundle assembly • transmembrane transport Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	119	11519
Ensembl	ENSG00000075340	ENSMUSG00000030000
UniProt	P35612	Q9QYB8
RefSeq (mRNA)	NM_001185054	NM_001271857
RefSeq (protein)	NP_001171983	NP_001258786
Location (UCSC)	Chr 2: 70.61 – 70.77 Mb	Chr 6: 86.08 – 86.12 Mb
PubMed search

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.^[2]

Interactions

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

References

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

Further reading

• Gilligan DM, Lieman J, Bennett V (1996). "Assignment of the human beta-adducin gene (ADD2) to 2p13-p14 by in situ hybridization". Genomics 28 (3): 610–2. doi:10.1006/geno.1995.1205. PMID 7490111.
• Hughes CA, Bennett V (1995). "Adducin: a physical model with implications for function in assembly of spectrin-actin complexes". J. Biol. Chem. 270 (32): 18990–6. doi:10.1074/jbc.270.32.18990. PMID 7642559.
• Miyazaki M, Kaibuchi K, Shirataki H; et al. (1995). "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. doi:10.1016/0169-328X(94)00180-M. PMID 7707875.
• Miyazaki M, Shirataki H, Kohno H; et al. (1995). "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. doi:10.1006/bbrc.1994.2688. PMID 7999065.
• White RA, Angeloni SV, Pasztor LM (1996). "Chromosomal localization of the beta-adducin gene to mouse chromosome 6 and human chromosome 2". Mamm. Genome 6 (10): 741–3. doi:10.1007/BF00354298. PMID 8563174.
• Tisminetzky S, Devescovi G, Tripodi G; et al. (1996). "Genomic organisation and chromosomal localisation of the gene encoding human beta adducin". Gene 167 (1–2): 313–6. doi:10.1016/0378-1119(95)00591-9. PMID 8566798.
• Matsuoka Y, Hughes CA, Bennett V (1996). "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. doi:10.1074/jbc.271.41.25157. PMID 8810272.
• Gilligan DM, Lozovatsky L, Silberfein A (1997). "Organization of the human beta-adducin gene (ADD2)". Genomics 43 (2): 141–8. doi:10.1006/geno.1997.4802. PMID 9244430.
• Matsuoka Y, Li X, Bennett V (1998). "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. doi:10.1083/jcb.142.2.485. PMC 2133059. PMID 9679146.
• Gilligan DM, Lozovatsky L, Gwynn B; et al. (1999). "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. doi:10.1073/pnas.96.19.10717. PMC 17949. PMID 10485892.
• Shima T, Okumura N, Takao T; et al. (2001). "Interaction of the SH2 domain of Fyn with a cytoskeletal protein, beta-adducin". J. Biol. Chem. 276 (45): 42233–40. doi:10.1074/jbc.M102699200. PMID 11526103.
• Strausberg RL, Feingold EA, Grouse LH; et al. (2003). "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. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Citterio L, Tizzoni L, Catalano M; et al. (2003). "Expression analysis of the human adducin gene family and evidence of ADD2 beta4 multiple splicing variants". Biochem. Biophys. Res. Commun. 309 (2): 359–67. doi:10.1016/j.bbrc.2003.08.011. PMID 12951058.
• Tikhonoff V, Kuznetsova T, Stolarz K; et al. (2004). "beta-Adducin polymorphisms, blood pressure, and sodium excretion in three European populations". Am. J. Hypertens. 16 (10): 840–6. doi:10.1016/S0895-7061(03)00975-0. PMID 14553963.
• Brandenberger R, Wei H, Zhang S; et al. (2005). "Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation". Nat. Biotechnol. 22 (6): 707–16. doi:10.1038/nbt971. PMID 15146197.
• Ballif BA, Villén J, Beausoleil SA; et al. (2005). "Phosphoproteomic analysis of the developing mouse brain". Mol. Cell Proteomics 3 (11): 1093–101. doi:10.1074/mcp.M400085-MCP200. PMID 15345747.
• Gerhard DS, Wagner L, Feingold EA; et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Efendiev R, Krmar RT, Ogimoto G; et al. (2005). "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. doi:10.1161/01.RES.0000149570.20845.89. PMID 15528469.
• Lanzani C, Citterio L, Jankaricova M; et al. (2005). "Role of the adducin family genes in human essential hypertension". J. Hypertens. 23 (3): 543–9. doi:10.1097/01.hjh.0000160210.48479.78. PMID 15716695.