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Gene Section Mini Review Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS Gene Section Mini Review SORBS2 (sorbin and SH3 domain containing 2) Jean-Loup Huret Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France (JLH) Published in Atlas Database: August 2008 Online updated version : http://AtlasGeneticsOncology.org/Genes/SORBS2ID693ch4q35.html DOI: 10.4267/2042/44517 This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence. © 2009 Atlas of Genetics and Cytogenetics in Oncology and Haematology Identity Function Adaptor protein. Other names: ARGBP2 (Arg/Abl-interacting protein Signaling proteins like ABL1 and ABL2 (ARG) (1q25) 2); FLJ93447; KIAA0777; PRO0618 associate with and phosphorylate SORBS2 (Wang et HGNC (Hugo): SORBS2 al., 1997). Location: 4q35.1 SORBS2 negatively regulates ABL1 and ABL2 by recruiting CBL (11q23.3) in a complex with ABL1, DNA/RNA facilitating phosphorylation of CBL by ABL1 and promoting CBL-directed ubiquitination and Transcription degradation of ABL1 and SORBS2 in the proteasome Various transcripts. (Soubeyran et al., 2003). Role in AKT/PAK1 cell survival pathway: Protein ArgBP2gamma (another SORBS2 splice) interacts with AKT and PAK1. Expression of ArgBP2gamma induces Description PAK1 activity and overrides apoptosis induced by The N-term region of the protein contains a sorbin ectopic expression of BAD or DNA damage (Yuan et homology (SoHo) domain. Sorbin, a 153 amino acid al., 2005). peptide, was isolated from porcine intestine (Vagne- Cytoskeletal proteins: SORBS2 also binds VCL Descroix et al., 1991). As a matter of fact, human (vinculin) (10q22) a protein which plays an important sorbin is spliced from an alternative transcript from the role in cell adhesion and migration, and MLLT4 (also SORBS2/ArgBP2 gene locus (Hand and Eiden, 2005). called AF6 or afadin) (6q27), another component of The sorbin homology domain is a motif for the cell membranes at specialized sites of cell-cell contact targeting of proteins to lipid rafts (Kimura et al., 2001); (Kawabe et al., 1999). 3 proteins present the SoHo domain: SORBS2/ArgBP2, SORBS2 has been found to localize at the Z-disks of SORBS1 (also called c-Cbl-associated protein (CAP), cardiac myofibrils, indicating that ArgBP2 has a or ponsin) (10q24), and SORBS3 (vinexin) (8p21). The specialized function associated with the contractile C-term region of the three SORBS genes contains 3 apparatus of cardiac muscle (Wang et al., 1997). SH3 domains. The three genes share the same SORBS2 binds alpha actinin, an actin crosslinking structural organization and present overlapping protein and a major component of the Z-disks, and functions. PALLD (palladin) (4q32), a protein associated with the alpha actinin network. Expression SORBS2 co-localize with ABL1 in actin stress fibers Widely expressed; very abundant in heart. (bundles of actin filaments which appear/disappear upon stimuli) (Wang et al., 1997). Localisation nArgBP2, a spliced form of SORB2 with a zinc finger Cytoplasm and nucleus (like its partner ABL1). motif in the central part of the protein, is found in the Atlas Genet Cytogenet Oncol Haematol. 2009; 13(7) 497 SORBS2 (sorbin and SH3 domain containing 2) Huret JL post-synaptic densities and binds DLGAP1 (SAPAP, 18p11) (Kawabe et al., 1999). References SORBS2 also interacts with SPTAN1 (alpha 2- Golvan YJ, Houin R, Combes C, Deniau M, Lancastre F. spectrin) (9q34), another component of the membrane- [Natural transmission of Schistosoma mansoni in Guadeloupe (French Antilles). Preliminary note (author's transl)]. Ann associated cytoskeleton, DNM1 (9q34) and DNM2 Parasitol Hum Comp. 1977 May-Jun;52(3):259-75 (19p13) (dynamins) (GTPases implicated in the regulation of actin dynamics and abundantly found in Vagne-Descroix M, Pansu D, Jörnvall H, Carlquist M, Guignard H, Jourdan G, Desvigne A, Collinet M, Caillet C, Mutt V. the brain), WASF2 (1p36), and SYNJ2 (synaptojanin Isolation and characterisation of porcine sorbin. Eur J 2) (6q25), the last two undergo ubiquitination and Biochem. 1991 Oct 1;201(1):53-9 ABL1-dependent tyrosine phosphorylation (Cestra et Kawabe H, Hata Y, Takeuchi M, Ide N, Mizoguchi A, Takai Y. al., 2005). nArgBP2, a novel neural member of ponsin/ArgBP2/vinexin ABL1 plays an important role in axonogenesis; ABL1 family that interacts with synapse-associated protein and ABL2 localize to the pre- and postsynaptic 90/postsynaptic density-95-associated protein (SAPAP). J Biol compartments of synapses. Chem. 1999 Oct 22;274(43):30914-8 SORBS2 binds WASF1 (also called WAVE1) (6q21) Kimura A, Baumann CA, Chiang SH, Saltiel AR. The sorbin and PTPN12 (7q11). PTPN12, a protein tyrosine homology domain: a motif for the targeting of proteins to lipid phosphatase, prevents SORBS2 phosphorylation by rafts. Proc Natl Acad Sci U S A. 2001 Jul 31;98(16):9098-103 ABL1. Phosphorylation of WASF1 induced by the Kioka N, Ueda K, Amachi T. Vinexin, CAP/ponsin, ArgBP2: a overexpression of ABL1 was enhanced in the presence novel adaptor protein family regulating cytoskeletal organization and signal transduction. Cell Struct Funct. 2002 of SORBS2, and overexpression of PTPN12 abolished Feb;27(1):1-7 the ABL1-mediated phosphorylation of WASF1 (Taieb Soubeyran P, Barac A, Szymkiewicz I, Dikic I. Cbl-ArgBP2 et al., 2008). complex mediates ubiquitination and degradation of c-Abl. SORBS2 inhibits adhesion and migration of pancreatic Biochem J. 2003 Feb 15;370(Pt 1):29-34 cells (Taieb et al., 2008). Haglund K, Ivankovic-Dikic I, Shimokawa N, Kruh GD, Dikic I. Lipid rafts: SORBS2 links via its SH3 domains with Recruitment of Pyk2 and Cbl to lipid rafts mediates signals proline-rich motifs of CBL and that of PTK2B (PYK2) important for actin reorganization in growing neurites. J Cell (8p21) in a complex that is recruited to lipid rafts (via Sci. 2004 May 15;117(Pt 12):2557-68 its SoHo domain) following growth factor stimulation, Hernández SE, Krishnaswami M, Miller AL, Koleske AJ. How partially co-localizing with actin, which appears to be do Abl family kinases regulate cell shape and movement? critical for cytoskeletal rearrangements in growing Trends Cell Biol. 2004 Jan;14(1):36-44 neurites (Haglund et al., 2004). Cestra G, Toomre D, Chang S, De Camilli P. The Abl/Arg substrate ArgBP2/nArgBP2 coordinates the function of multiple Homology regulatory mechanisms converging on the actin cytoskeleton. SORBS1 and SORBS3. Proc Natl Acad Sci U S A. 2005 Feb 1;102(5):1731-6 Hand D, Eiden LE. Human sorbin is generated via splicing of Implicated in an alternative transcript from the ArgBP2 gene locus. Peptides. 2005 Jul;26(7):1278-82 t(4;11)(q35;q23) in acute myeloid Rönty M, Taivainen A, Moza M, Kruh GD, Ehler E, Carpen O. leukemia --> SORBS2 - MLL Involvement of palladin and alpha-actinin in targeting of the Abl/Arg kinase adaptor ArgBP2 to the actin cytoskeleton. Exp Hybrid/Mutated gene Cell Res. 2005 Oct 15;310(1):88-98 5' MLL - 3' SORBS2 Yuan ZQ, Kim D, Kaneko S, Sussman M, Bokoch GM, Kruh Pancreas cancer GD, Nicosia SV, Testa JR, Cheng JQ. ArgBP2gamma interacts with Akt and p21-activated kinase-1 and promotes cell survival. Oncogenesis J Biol Chem. 2005 Jun 3;280(22):21483-90 SORBS2 is repressed during pancreas carcinogenesis Pession A, Lo Nigro L, Montemurro L, Serravalle S, Fazzina R, and during progression of the disease. The antitumoral Izzi G, Nucifora G, Slany R, Tonelli R. ArgBP2, encoding a potential of SORBS2 appears to be linked to the control negative regulator of ABL, is fused to MLL in a case of infant of cell adhesion and migration (inhibition of cell M5 acute myeloid leukemia involving 4q35 and 11q23. Leukemia. 2006 Jul;20(7):1310-3 migration) rather than to the regulation of cell proliferation or sensitivity to apoptosis (Taieb et al., Taieb D, Roignot J, André F, Garcia S, Masson B, Pierres A, 2008). Iovanna JL, Soubeyran P. ArgBP2-dependent signaling regulates pancreatic cell migration, adhesion, and tumorigenicity. Cancer Res. 2008 Jun 15;68(12):4588-96 This article should be referenced as such: Huret JL. SORBS2 (sorbin and SH3 domain containing 2). Atlas Genet Cytogenet Oncol Haematol. 2009; 13(7):497-498. Atlas Genet Cytogenet Oncol Haematol. 2009; 13(7) 498 .
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