| ||AGAP1 (2q37.2)::SORBS2 (4q35.1)||C6orf106 (6p21.31)::SORBS2 (4q35.1)||KMT2A (11q23.3)::SORBS2 (4q35.1)|
||NUDT3 (6p21.31)::SORBS2 (4q35.1)||PDLIM3 (4q35.1)::SORBS2 (4q35.1)||R3HDM2 (12q13.3)::SORBS2 (4q35.1)|
||RAI14 (5p13.2)::SORBS2 (4q35.1)||SORBS2 (4q35.1)::AIF1 (6p21.33)||SORBS2 (4q35.1)::ARHGAP27 (17q21.31)|
||SORBS2 (4q35.1)::CCDC34 (11p14.1)||SORBS2 (4q35.1)::CKB (14q32.32)||SORBS2 (4q35.1)::LRMDA (10q22.2)|
||SORBS2 (4q35.1)::PDLIM5 (4q22.3)||SORBS2 (4q35.1)::PHLPP2 (16q22.2)||SORBS2 (4q35.1)::PLAGL1 (6q24.2)|
||SORBS2 (4q35.1)::SORBS2 (4q35.1)||SORBS2 (4q35.1)::TNRC6A (16p12.1)|
|Description|| The N-term region of the protein contains a sorbin homology (SoHo) domain. Sorbin, a 153 amino acid peptide, was isolated from porcine intestine (Vagne-Descroix et al., 1991). As a matter of fact, human sorbin is spliced from an alternative transcript from the SORBS2/ArgBP2 gene locus (Hand and Eiden, 2005). The sorbin homology domain is a motif for the targeting of proteins to lipid rafts (Kimura et al., 2001); 3 proteins present the SoHo domain: SORBS2/ArgBP2, SORBS1 (also called c-Cbl-associated protein (CAP), or ponsin) (10q24), and SORBS3 (vinexin) (8p21). The C-term region of the three SORBS genes contains 3 SH3 domains. The three genes share the same structural organization and present overlapping functions.|
|Expression|| Widely expressed; very abundant in heart.|
|Localisation|| Cytoplasm and nucleus (like its partner ABL1).|
|Function|| Adaptor protein.|
Signaling proteins like ABL1 and ABL2 (ARG) (1q25) associate with and phosphorylate SORBS2 (Wang et al., 1997).
SORBS2 negatively regulates ABL1 and ABL2 by recruiting CBL (11q23.3) in a complex with ABL1, facilitating phosphorylation of CBL by ABL1 and promoting CBL-directed ubiquitination and degradation of ABL1 and SORBS2 in the proteasome (Soubeyran et al., 2003).
Role in AKT/PAK1 cell survival pathway: ArgBP2gamma (another SORBS2 splice) interacts with AKT and PAK1. Expression of ArgBP2gamma induces PAK1 activity and overrides apoptosis induced by ectopic expression of BAD or DNA damage (Yuan et al., 2005).
Cytoskeletal proteins: SORBS2 also binds VCL (vinculin) (10q22) a protein which plays an important role in cell adhesion and migration, and MLLT4 (also called AF6 or afadin) (6q27), another component of cell membranes at specialized sites of cell-cell contact (Kawabe et al., 1999).
SORBS2 has been found to localize at the Z-disks of cardiac myofibrils, indicating that ArgBP2 has a specialized function associated with the contractile apparatus of cardiac muscle (Wang et al., 1997). SORBS2 binds alpha actinin, an actin crosslinking protein and a major component of the Z-disks, and PALLD (palladin) (4q32), a protein associated with the alpha actinin network.
SORBS2 co-localize with ABL1 in actin stress fibers (bundles of actin filaments which appear/disappear upon stimuli) (Wang et al., 1997).
nArgBP2, a spliced form of SORB2 with a zinc finger motif in the central part of the protein, is found in the post-synaptic densities and binds DLGAP1 (SAPAP, 18p11) (Kawabe et al., 1999).
SORBS2 also interacts with SPTAN1 (alpha 2-spectrin) (9q34), another component of the membrane-associated cytoskeleton, DNM1 (9q34) and DNM2 (19p13) (dynamins) (GTPases implicated in the regulation of actin dynamics and abundantly found in the brain), WASF2 (1p36), and SYNJ2 (synaptojanin 2) (6q25), the last two undergo ubiquitination and ABL1-dependent tyrosine phosphorylation (Cestra et al., 2005).
ABL1 plays an important role in axonogenesis; ABL1 and ABL2 localize to the pre- and postsynaptic compartments of synapses.
SORBS2 binds WASF1 (also called WAVE1) (6q21) and PTPN12 (7q11). PTPN12, a protein tyrosine phosphatase, prevents SORBS2 phosphorylation by ABL1. Phosphorylation of WASF1 induced by the overexpression of ABL1 was enhanced in the presence of SORBS2, and overexpression of PTPN12 abolished the ABL1-mediated phosphorylation of WASF1 (Taieb et al., 2008).
SORBS2 inhibits adhesion and migration of pancreatic cells (Taieb et al., 2008).
Lipid rafts: SORBS2 links via its SH3 domains with proline-rich motifs of CBL and that of PTK2B (PYK2) (8p21) in a complex that is recruited to lipid rafts (via its SoHo domain) following growth factor stimulation, partially co-localizing with actin, which appears to be critical for cytoskeletal rearrangements in growing neurites (Haglund et al., 2004).
|Homology|| SORBS1 and SORBS3.|
| The Abl/Arg substrate ArgBP2/nArgBP2 coordinates the function of multiple regulatory mechanisms converging on the actin cytoskeleton.|
| Cestra G, Toomre D, Chang S, De Camilli P.|
| Proc Natl Acad Sci U S A. 2005 Feb 1;102(5):1731-6.|
| Recruitment of Pyk2 and Cbl to lipid rafts mediates signals important for actin reorganization in growing neurites.|
| Haglund K, Ivankovic-Dikic I, Shimokawa N, Kruh GD, Dikic I.|
| J Cell Sci. 2004 May 15;117(Pt 12):2557-68.|
| Human sorbin is generated via splicing of an alternative transcript from the ArgBP2 gene locus.|
| Hand D, Eiden LE.|
| Peptides. 2005 Jul;26(7):1278-82.|
| How do Abl family kinases regulate cell shape and movement?|
| Hernandez SE, Krishnaswami M, Miller AL, Koleske AJ.|
| Trends Cell Biol. 2004 Jan;14(1):36-44. (Review)|
| nArgBP2, a novel neural member of ponsin/ArgBP2/vinexin family that interacts with synapse-associated protein 90/postsynaptic density-95-associated protein (SAPAP).|
| Kawabe H, Hata Y, Takeuchi M, Ide N, Mizoguchi A, Takai Y.|
| J Biol Chem. 1999 Oct 22;274(43):30914-8.|
| The sorbin homology domain: a motif for the targeting of proteins to lipid rafts.|
| Kimura A, Baumann CA, Chiang SH, Saltiel AR.|
| Proc Natl Acad Sci U S A. 2001 Jul 31;98(16):9098-103.|
| Vinexin, CAP/ponsin, ArgBP2: a novel adaptor protein family regulating cytoskeletal organization and signal transduction.|
| Kioka N, Ueda K, Amachi T.|
| Cell Struct Funct. 2002 Feb;27(1):1-7. (Review)|
| ArgBP2, encoding a negative regulator of ABL, is fused to MLL in a case of infant M5 acute myeloid leukemia involving 4q35 and 11q23.|
| Pession A, Lo Nigro L, Montemurro L, Serravalle S, Fazzina R, Izzi G, Nucifora G, Slany R, Tonelli R.|
| Leukemia. 2006 Jul;20(7):1310-3.|
| Involvement of palladin and alpha-actinin in targeting of the Abl/Arg kinase adaptor ArgBP2 to the actin cytoskeleton.|
| Ronty M, Taivainen A, Moza M, Kruh GD, Ehler E, Carpen O.|
| Exp Cell Res. 2005 Oct 15;310(1):88-98.|
| Cbl-ArgBP2 complex mediates ubiquitination and degradation of c-Abl.|
| Soubeyran P, Barac A, Szymkiewicz I, Dikic I.|
| Biochem J. 2003 Feb 15;370(Pt 1):29-34.|
| ArgBP2-dependent signaling regulates pancreatic cell migration, adhesion, and tumorigenicity.|
| Taieb D, Roignot J, Andre F, Garcia S, Masson B, Pierres A, Iovanna JL, Soubeyran P.|
| Cancer Res. 2008 Jun 15;68(12):4588-96.|
| Isolation and characterisation of porcine sorbin.|
| Vagne-Descroix M, Pansu D, Jornvall H, Carlquist M, Guignard H, Jourdan G, Desvigne A, Collinet M, Caillet C, Mutt V.|
| Eur J Biochem. 1991 Oct 1;201(1):53-9.|
| ArgBP2, a multiple Src homology 3 domain-containing, Arg/Abl-interacting protein, is phosphorylated in v-Abl-transformed cells and localized in stress fibers and cardiocyte Z-disks.|
| Wang B, Golemis EA, Kruh GD.|
| J Biol Chem. 1997 Jul 11;272(28):17542-50.|
| ArgBP2gamma interacts with Akt and p21-activated kinase-1 and promotes cell survival.|
| Yuan ZQ, Kim D, Kaneko S, Sussman M, Bokoch GM, Kruh GD, Nicosia SV, Testa JR, Cheng JQ.|
| J Biol Chem. 2005 Jun 3;280(22):21483-90.|