Alternative titles; symbols
HGNC Approved Gene Symbol: SORBS2
Cytogenetic location: 4q35.1 Genomic coordinates (GRCh38): 4:185,585,523-185,956,372 (from NCBI)
By sequencing clones obtained from a size-fractionated human brain cDNA library, Nagase et al. (1998) cloned SORBS2, which they designated KIAA0777. The deduced 1,100-amino acid protein shares 87.9% identity with rat Sorbs2. RT-PCR ELISA detected highest SORBS2 expression in human heart, followed by brain, ovary, liver, kidney, and pancreas. Lower expression was detected in lung, skeletal muscle, spleen, and testis.
Using the 3 C-terminal SH3-binding sites of ARG (ABL2; 164690) as bait in a yeast 2-hybrid screen of a human brain cDNA library, Wang et al. (1997) obtained 2 splice variants of SORBS2 that they called ARGBP2A and ARGBP2B. The deduced ARGBP2A isoform contains 666 amino acids and has a calculated molecular mass of approximately 75 kD. It has a potential nuclear localization sequence, followed by a serine- and threonine-rich stretch and 3 C-terminal SH3 motifs separated by proline-rich spacers. ARGBP2A also has 5 consensus ABL (ABL1; 189980) tyrosine phosphorylation sites. The deduced 645-amino acid ARGBP2B isoform has a distinct sequence in the middle of the protein and lacks the third SH3 domain. Northern blot analysis detected ARGBP2 expression in all 16 human tissues examined except peripheral leukocytes, with heart showing highest expression. ARGBP2 transcripts of 4.4, 5, and 5.8 kb exhibited variable and tissue-specific expression, and a transcript of 6.6 kb was detected in brain only. Immunohistochemical analysis localized Argbp2 at Z discs of chicken embryo cardiac myofibrils and at stress fibers of PtK2 marsupial kidney epithelial cells. Transfected ARGBP2A localized to stress fibers. Staining of stress fibers showed periodic beaded structures, termed dense bodies, at which actin filaments were anchored. Transfected ARGBP2B localized to the nucleus.
Porcine sorbin is expressed in the gastrointestinal system and the enteric nervous system and has a role in intestinal absorption and secretion. By database analysis, Hand and Eiden (2005) identified the human ortholog of porcine sorbin as a splice variant of ARGBP2. The deduced 153-amino acid porcine and human proteins exhibit 93% identity.
Using an in vitro binding assay, Wang et al. (1997) found that SH3 domains 1 and 3 of human ARGBP2A bound proline-rich motif-2 of ARG. The 2 proteins also interacted in insect cells infected with ARGBP2A and murine virus v-Abl and in transformed NIH3T3 cells. Endogenous Argbp2 was phosphorylated on tyrosine residues in NIH3T3 cells transformed by v-Abl.
Taieb et al. (2008) found that ARGBP2 had antitumor potential in pancreatic cancer (see 260350) cells. Expression of ARGBP2 was downregulated in pancreatic adenocarcinomas. ARGBP2 inhibited adhesion and migration of pancreatic cells via its interaction with PTP-PEST (PTPN12; 600079) and WAVE1 (WASF1; 605035), which regulate actin dynamics.
Hand and Eiden (2005) determined that the SORBS2 gene contains at least 11 exons.
By genomic sequence analysis, Hand and Eiden (2005) mapped the SORBS2 gene to chromosome 4q35.1.
The article in which Yuan et al. (2005) reported the identification of a splice variant of the ARGBP2 gene, which they called ARGBP2-gamma, and discussed its interaction with AKT1 (164730), PAK1 (602590), and BAD (603167), was retracted.
Hand, D., Eiden, L. E. Human sorbin is generated via splicing of an alternative transcript from the ArgBP2 gene locus. Peptides 26: 1278-1282, 2005. [PubMed: 15949647] [Full Text: https://doi.org/10.1016/j.peptides.2005.01.016]
Nagase, T., Ishikawa, K., Suyama, M., Kikuno, R., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., Ohara, O. Prediction of the coding sequences of unidentified human genes. XI. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 5: 277-286, 1998. [PubMed: 9872452] [Full Text: https://doi.org/10.1093/dnares/5.5.277]
Taieb, D., Roignot, J., Andre, F., Garcia, S., Masson, B., Pierres, A., Iovanna, J.-L., Soubeyran, P. ArgBP2-dependent signaling regulates pancreatic cell migration, adhesion, and tumorigenicity. Cancer Res. 68: 4588-4596, 2008. [PubMed: 18559503] [Full Text: https://doi.org/10.1158/0008-5472.CAN-08-0958]
Wang, B., Golemis, E. A., Kruh, G. D. 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. J. Biol. Chem. 272: 17542-17550, 1997. [PubMed: 9211900] [Full Text: https://doi.org/10.1074/jbc.272.28.17542]
Yuan, Z., Kim, D., Kaneko, S., Sussman, M., Bokoch, G. M., Kruh, G. D., Nicosia, S. V., Testa, J. R., Cheng, J. Q. ArgBP2-gamma interacts with Akt and p21-activated kinase-1 and promotes cell survival. J. Biol. Chem. 280: 21483-21490, 2005. Note: Retraction: J. Biol. Chem. 291: 22845 only, 2016. [PubMed: 15784622] [Full Text: https://doi.org/10.1074/jbc.M500097200]