SORBS2 explained

ArgBP2 protein, also referred to as Sorbin and SH3 domain-containing protein 2 is a protein that in humans is encoded by the SORBS2 gene.^{[1] [2]} ArgBP2 belongs to the a small family of adaptor proteins having sorbin homology (SOHO) domains. ArgBP2 is highly abundant in cardiac muscle cells at sarcomeric Z-disc structures, and is expressed in other cells at actin stress fibers and the nucleus.

Structure

ArgBP2 may exist in as many as 9 unique isoforms ranging from 52 kDa to 117 kDa (492 to 1100 amino acids).^[2] ArgBP2 belongs to the a small family of adaptor proteins having sorbin homology (SOHO) domains and three SH3 domains, which regulate cell adhesion, cytoskeletal organization and growth factor signaling; other members include CAP/ponsin and vinexin.^[3] The three SH3 domains are C-terminal, a serine-threonine rich domain^[4] resides in the middle, and the sorbin homology (SoHo) domain is N-terminal. The SH3 domains interact with Arg/Abl, vinculin.^[3] The SOHO domain interacts with flotillin found in lipid rafts.^[5]

Function

The subcellular localization of this protein in epithelial and cardiac muscle cells suggests that ArgBP2 functions as an adapter protein to assemble signaling complexes in stress fibers, and that it is a potential link between Abl family kinases and the actin cytoskeleton. ArgBP2 contains several potential Abl phosphorylation sites;^[4] Arg and c-Abl represent the mammalian members of the Abelson family of non-receptor protein-tyrosine kinases. In non-muscle cells, ArgBP2 bids Cbl which enhances the degradation of c-Abl;^[6] and also Pyk2 which promotes cytoskeletal remodeling.^[7] ArgBP2 binding with flotillin at lipid rafts may indicate a role for ArgBP2 in vesicle trafficking and signal transduction. flotillin in skeletal muscle cells exhibits a striated pattern^[8] suggesting localization to T-tubules or sarcoplasmic reticular cisternae, though no precise role has been determined in cardiac cells. In cardiac muscle cells, pull-down experiments discovered ArgBP2 in complex with alpha actinin-2, vinculin, spectrin, paxillin, Pyk2 and flotillin, suggesting that ArgBP2 may be involved in myofibril assembly and Z-band signaling in cardiomyocytes,^[9] though functional studies are necessary to elucidate specific mechanisms. ArgBP2 has been linked to hypertrophic signaling, as a potent paracrine-acting RNA molecule shown to induce cardiac hypertrophy in mice, miR-21, acts on both ArgBP2 and PDLIM5 to trigger the hypertrophic response.^[10]

Clinical Significance

Elevated levels of serum ArgBP2 and coordinate decreases in ArgBP2 in myocardial tissue were detected in the very early phase from patients post-myocardial infarction who died within 7 hours of the insult.^[11] Chromosome 4 pericentric inversion has been observed in 10 patients, with associated cardiac defects linked to terminal 4q35.1 deletions, which may affect SORBS2.^[12]

Interactions

ArgBP2 has been shown to interact with:

• ABL,^[1]
• ABL2,
• ACTC1,^{[9] [13]}
• CBL,^[14]
• FLOT1,^[15]
• PTK2B,^[16]
• PLDN,^[17] and
• VCL.^{[9] [18]}

Further reading

• Kioka N . [A novel adaptor protein family regulating cytoskeletal organization and signal transduction--Vinexin, CAP/ponsin, ArgBP2] . Seikagaku. The Journal of Japanese Biochemical Society . 74 . 11 . 1356–60 . Nov 2002 . 12510380 .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . Jan 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Hillier LD, Lennon G, Becker M, Bonaldo MF, Chiapelli B, Chissoe S, Dietrich N, DuBuque T, Favello A, Gish W, Hawkins M, Hultman M, Kucaba T, Lacy M, Le M, Le N, Mardis E, Moore B, Morris M, Parsons J, Prange C, Rifkin L, Rohlfing T, Schellenberg K, Bento Soares M, Tan F, Thierry-Meg J, Trevaskis E, Underwood K, Wohldman P, Waterston R, Wilson R, Marra M . Generation and analysis of 280,000 human expressed sequence tags . Genome Research . 6 . 9 . 807–28 . Sep 1996 . 8889549 . 10.1101/gr.6.9.807 . free .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . Oct 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Kawabe H, Hata Y, Takeuchi M, Ide N, Mizoguchi A, Takai Y . nArgBP2, a novel neural member of ponsin/ArgBP2/vinexin family that interacts with synapse-associated protein 90/postsynaptic density-95-associated protein (SAPAP) . The Journal of Biological Chemistry . 274 . 43 . 30914–8 . Oct 1999 . 10521485 . 10.1074/jbc.274.43.30914 . free .
• Hartley JL, Temple GF, Brasch MA . DNA cloning using in vitro site-specific recombination . Genome Research . 10 . 11 . 1788–95 . Nov 2000 . 11076863 . 310948 . 10.1101/gr.143000 .
• Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Böcher M, Blöcker H, Bauersachs S, Blum H, Lauber J, Düsterhöft A, Beyer A, Köhrer K, Strack N, Mewes HW, Ottenwälder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A . Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs . Genome Research . 11 . 3 . 422–35 . Mar 2001 . 11230166 . 311072 . 10.1101/gr.GR1547R .
• Zucconi A, Dente L, Santonico E, Castagnoli L, Cesareni G . Selection of ligands by panning of domain libraries displayed on phage lambda reveals new potential partners of synaptojanin 1 . Journal of Molecular Biology . 307 . 5 . 1329–39 . Apr 2001 . 11292345 . 10.1006/jmbi.2001.4572 .
• Kimura A, Baumann CA, Chiang SH, Saltiel AR . The sorbin homology domain: a motif for the targeting of proteins to lipid rafts . Proceedings of the National Academy of Sciences of the United States of America . 98 . 16 . 9098–103 . Jul 2001 . 11481476 . 55379 . 10.1073/pnas.151252898 . 2001PNAS...98.9098K . free .
• Xu YC, Wu RF, Gu Y, Yang YS, Yang MC, Nwariaku FE, Terada LS . Involvement of TRAF4 in oxidative activation of c-Jun N-terminal kinase . The Journal of Biological Chemistry . 277 . 31 . 28051–7 . Aug 2002 . 12023963 . 10.1074/jbc.M202665200 . free .
• Nakayama M, Kikuno R, Ohara O . Protein-protein interactions between large proteins: two-hybrid screening using a functionally classified library composed of long cDNAs . Genome Research . 12 . 11 . 1773–84 . Nov 2002 . 12421765 . 187542 . 10.1101/gr.406902 .
• Soubeyran P, Barac A, Szymkiewicz I, Dikic I . Cbl-ArgBP2 complex mediates ubiquitination and degradation of c-Abl . The Biochemical Journal . 370 . Pt 1 . 29–34 . Feb 2003 . 12475393 . 1223168 . 10.1042/BJ20021539 .
• Haglund K, Ivankovic-Dikic I, Shimokawa N, Kruh GD, Dikic I . Recruitment of Pyk2 and Cbl to lipid rafts mediates signals important for actin reorganization in growing neurites . Journal of Cell Science . 117 . Pt 12 . 2557–68 . May 2004 . 15128873 . 10.1242/jcs.01148 . free .
• Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP . Large-scale characterization of HeLa cell nuclear phosphoproteins . Proceedings of the National Academy of Sciences of the United States of America . 101 . 33 . 12130–5 . Aug 2004 . 15302935 . 514446 . 10.1073/pnas.0404720101 . 2004PNAS..10112130B . free .
• Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, Bechtel S, Sauermann M, Korf U, Pepperkok R, Sültmann H, Poustka A . From ORFeome to biology: a functional genomics pipeline . Genome Research . 14 . 10B . 2136–44 . Oct 2004 . 15489336 . 528930 . 10.1101/gr.2576704 .

Notes and References

1. Wang B, Golemis EA, Kruh GD . 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 . The Journal of Biological Chemistry . 272 . 28 . 17542–50 . Jul 1997 . 9211900 . 10.1074/jbc.272.28.17542 . free . 20.500.12613/9174 . free .
2. Web site: Entrez Gene: SORBS2 sorbin and SH3 domain containing 2.
3. Kioka N, Ueda K, Amachi T . Vinexin, CAP/ponsin, ArgBP2: a novel adaptor protein family regulating cytoskeletal organization and signal transduction . Cell Structure and Function . 27 . 1 . 1–7 . Feb 2002 . 11937713 . 10.1247/csf.27.1. free .
4. Wang B, Golemis EA, Kruh GD . 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 . The Journal of Biological Chemistry . 272 . 28 . 17542–50 . Jul 1997 . 9211900 . 10.1074/jbc.272.28.17542. free . 20.500.12613/9174 . free .
5. Kimura A, Baumann CA, Chiang SH, Saltiel AR . The sorbin homology domain: a motif for the targeting of proteins to lipid rafts . Proceedings of the National Academy of Sciences of the United States of America . 98 . 16 . 9098–103 . Jul 2001 . 11481476 . 10.1073/pnas.151252898 . 55379. 2001PNAS...98.9098K . free .
6. Soubeyran P, Barac A, Szymkiewicz I, Dikic I . Cbl-ArgBP2 complex mediates ubiquitination and degradation of c-Abl . The Biochemical Journal . 370 . Pt 1 . 29–34 . Feb 2003 . 12475393 . 10.1042/BJ20021539 . 1223168.
7. Haglund K, Ivankovic-Dikic I, Shimokawa N, Kruh GD, Dikic I . Recruitment of Pyk2 and Cbl to lipid rafts mediates signals important for actin reorganization in growing neurites . Journal of Cell Science . 117 . Pt 12 . 2557–68 . May 2004 . 15128873 . 10.1242/jcs.01148 . free .
8. Voldstedlund M, Vinten J, Tranum-Jensen J . cav-p60 expression in rat muscle tissues. Distribution of caveolar proteins . Cell and Tissue Research . 306 . 2 . 265–76 . Nov 2001 . 11702238 . 10.1007/s004410100439 . 7420385 .
9. Sanger JM, Wang J, Gleason LM, Chowrashi P, Dube DK, Mittal B, Zhukareva V, Sanger JW . Arg/Abl-binding protein, a Z-body and Z-band protein, binds sarcomeric, costameric, and signaling molecules . Cytoskeleton . 67 . 12 . 808–23 . Dec 2010 . 20886612 . 10.1002/cm.20490 . 3019100.
10. Bang C, Batkai S, Dangwal S, Gupta SK, Foinquinos A, Holzmann A, Just A, Remke J, Zimmer K, Zeug A, Ponimaskin E, Schmiedl A, Yin X, Mayr M, Halder R, Fischer A, Engelhardt S, Wei Y, Schober A, Fiedler J, Thum T . Cardiac fibroblast-derived microRNA passenger strand-enriched exosomes mediate cardiomyocyte hypertrophy . The Journal of Clinical Investigation . 124 . 5 . 2136–46 . May 2014 . 24743145 . 10.1172/JCI70577 . 4001534.
11. Kakimoto Y, Ito S, Abiru H, Kotani H, Ozeki M, Tamaki K, Tsuruyama T . Sorbin and SH3 domain-containing protein 2 is released from infarcted heart in the very early phase: proteomic analysis of cardiac tissues from patients . Journal of the American Heart Association . 2 . 6 . e000565 . 24342996 . 10.1161/JAHA.113.000565 . 2013 . 3886759.
12. Maurin ML, Labrune P, Brisset S, Le Lorc'h M, Pineau D, Castel C, Romana S, Tachdjian G . Molecular cytogenetic characterization of a 4p15.1-pter duplication and a 4q35.1-qter deletion in a recombinant of chromosome 4 pericentric inversion . American Journal of Medical Genetics Part A . 149A . 2 . 226–31 . Feb 2009 . 19161154 . 10.1002/ajmg.a.32603 . 205310317 .
13. Sanger JM, Wang J, Gleason LM, Chowrashi P, Dube DK, Mittal B, Zhukareva V, Sanger JW . Dec 2010 . Arg/Abl-binding protein, a Z-body and Z-band protein, binds sarcomeric, costameric, and signaling molecules . Cytoskeleton . 67 . 12 . 808–23 . 20886612 . 3019100 . 10.1002/cm.20490.
14. Soubeyran P, Barac A, Szymkiewicz I, Dikic I . Feb 2003 . Cbl-ArgBP2 complex mediates ubiquitination and degradation of c-Abl . Biochem. J. . 370 . Pt 1 . 29–34 . 12475393 . 1223168 . 10.1042/BJ20021539.
15. Kimura A, Baumann CA, Chiang SH, Saltiel AR . Jul 2001 . The sorbin homology domain: a motif for the targeting of proteins to lipid rafts . Proc. Natl. Acad. Sci. U.S.A. . 98 . 16 . 9098–103 . 11481476 . 55379 . 10.1073/pnas.151252898. 2001PNAS...98.9098K . free .
16. Haglund K, Ivankovic-Dikic I, Shimokawa N, Kruh GD, Dikic I . May 2004 . Recruitment of Pyk2 and Cbl to lipid rafts mediates signals important for actin reorganization in growing neurites . J. Cell Sci. . 117 . Pt 12 . 2557–68 . 15128873 . 10.1242/jcs.01148. free .
17. Rönty M, Taivainen A, Moza M, Kruh GD, Ehler E, Carpen O . Oct 2005 . Involvement of palladin and alpha-actinin in targeting of the Abl/Arg kinase adaptor ArgBP2 to the actin cytoskeleton . Exp. Cell Res. . 310 . 1 . 88–98 . 16125169 . 10.1016/j.yexcr.2005.06.026.
18. Kioka N, Ueda K, Amachi T . Feb 2002 . Vinexin, CAP/ponsin, ArgBP2: a novel adaptor protein family regulating cytoskeletal organization and signal transduction . Cell Struct. Funct. . 27 . 1 . 1–7 . 11937713 . 10.1247/csf.27.1. free .