SORBS2

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.[5][6] 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.

SORBS2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4IGZ
Identifiers
Aliases	SORBS2, ARGBP2, PRO0618, sorbin and SH3 domain containing 2
External IDs	OMIM: 616349 MGI: 1924574 HomoloGene: 83295 GeneCards: SORBS2
Gene location (Human) Chr. Chromosome 4 (human)[1] Band 4q35.1 Start 185,585,444 bp[1] End 185,956,652 bp[1]
Gene location (Mouse) Chr. Chromosome 8 (mouse)[2] Band 8|8 B1.1 Start 45,507,788 bp[2] End 45,827,906 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • structural constituent of cytoskeleton • GO:0001948 protein binding • cytoskeletal adaptor activity • structural constituent of muscle • RNA binding • nucleic acid binding Cellular component • cytoplasm • cell projection • membrane • focal adhesion • cell membrane • cell junction • Z disc • apical plasma membrane • actin cytoskeleton • perinuclear region of cytoplasm • cell nucleus • lamellipodium • nucleoplasm Biological process • cell growth involved in cardiac muscle cell development • actin filament organization • Notch signaling pathway • biological process Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	8470	234214
Ensembl	ENSG00000154556	ENSMUSG00000031626
UniProt	O94875	Q3UTJ2
RefSeq (mRNA)	NM_001145670 NM_001145671 NM_001145672 NM_001145673 NM_001145674 NM_001145675 NM_001270771 NM_003603 NM_021069	NM_001205219 NM_172752 NM_001310707 NM_001310708
RefSeq (protein)	NP_001139142 NP_001139143 NP_001139144 NP_001139145 NP_001139146 NP_001139147 NP_001257700 NP_003594 NP_066547	NP_001192148 NP_001297636 NP_001297637 NP_766340
Location (UCSC)	Chr 4: 185.59 – 185.96 Mb	Chr 8: 45.51 – 45.83 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Structure

ArgBP2 may exist in as many as 9 unique isoforms ranging from 52 kDa to 117 kDa (492 to 1100 amino acids).[6] 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.[7] The three SH3 domains are C-terminal, a serine-threonine rich domain[8] resides in the middle, and the sorbin homology (SoHo) domain is N-terminal. The SH3 domains interact with Arg/Abl, vinculin.[7] The SOHO domain interacts with flotillin found in lipid rafts.[9]

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;[8] 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;[10] and also Pyk2 which promotes cytoskeletal remodeling.[11] 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[12] 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,[13] though functional studies are necessary to elucidate specific mechanisms. ArgBP2 has been linked to hyertrophic 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.[14]

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.[15] Chromosome 4 pericentric inversion has been observed in 10 patients, with associated cardiac defects linked to terminal 4q35.1 deletions, which may affect SORBS2.[16]

Interactions

ArgBP2 has been shown to interact with:

• ABL,[5][17]
• ABL2,[5]
• ACTC1,[13][18]
• CBL,[17][19]
• FLOT1,[20]
• PTK2B,[19]
• PLDN,[21] and
• VCL.[13][22]

References

1. GRCh38: Ensembl release 89: ENSG00000154556 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000031626 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Wang B, Golemis EA, Kruh GD (Jul 1997). "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. doi:10.1074/jbc.272.28.17542. PMID 9211900.
6. "Entrez Gene: SORBS2 sorbin and SH3 domain containing 2".
7. Kioka N, Ueda K, Amachi T (Feb 2002). "Vinexin, CAP/ponsin, ArgBP2: a novel adaptor protein family regulating cytoskeletal organization and signal transduction". Cell Structure and Function. 27 (1): 1–7. doi:10.1247/csf.27.1. PMID 11937713.
8. Wang B, Golemis EA, Kruh GD (Jul 1997). "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. doi:10.1074/jbc.272.28.17542. PMID 9211900.
9. Kimura A, Baumann CA, Chiang SH, Saltiel AR (Jul 2001). "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. doi:10.1073/pnas.151252898. PMC 55379. PMID 11481476.
10. Soubeyran P, Barac A, Szymkiewicz I, Dikic I (Feb 2003). "Cbl-ArgBP2 complex mediates ubiquitination and degradation of c-Abl". The Biochemical Journal. 370 (Pt 1): 29–34. doi:10.1042/BJ20021539. PMC 1223168. PMID 12475393.
11. 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". Journal of Cell Science. 117 (Pt 12): 2557–68. doi:10.1242/jcs.01148. PMID 15128873.
12. Voldstedlund M, Vinten J, Tranum-Jensen J (Nov 2001). "cav-p60 expression in rat muscle tissues. Distribution of caveolar proteins". Cell and Tissue Research. 306 (2): 265–76. doi:10.1007/s004410100439. PMID 11702238.
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. doi:10.1002/cm.20490. PMC 3019100. PMID 20886612.
14. 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 (May 2014). "Cardiac fibroblast-derived microRNA passenger strand-enriched exosomes mediate cardiomyocyte hypertrophy". The Journal of Clinical Investigation. 124 (5): 2136–46. doi:10.1172/JCI70577. PMC 4001534. PMID 24743145.
15. Kakimoto Y, Ito S, Abiru H, Kotani H, Ozeki M, Tamaki K, Tsuruyama T (2013). "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. doi:10.1161/JAHA.113.000565. PMC 3886759. PMID 24342996.
16. Maurin ML, Labrune P, Brisset S, Le Lorc'h M, Pineau D, Castel C, Romana S, Tachdjian G (Feb 2009). "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. doi:10.1002/ajmg.a.32603. PMID 19161154.
17. 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. doi:10.1042/BJ20021539. PMC 1223168. PMID 12475393.
18. 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. doi:10.1002/cm.20490. PMC 3019100. PMID 20886612.
19. 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. doi:10.1242/jcs.01148. PMID 15128873.
20. 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. doi:10.1073/pnas.151252898. PMC 55379. PMID 11481476.
21. 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. doi:10.1016/j.yexcr.2005.06.026. PMID 16125169.
22. 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. doi:10.1247/csf.27.1. PMID 11937713.

Further reading

• Kioka N (Nov 2002). "[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. PMID 12510380.
• Maruyama K, Sugano S (Jan 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• 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 (Sep 1996). "Generation and analysis of 280,000 human expressed sequence tags". Genome Research. 6 (9): 807–28. doi:10.1101/gr.6.9.807. PMID 8889549.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Kawabe H, Hata Y, Takeuchi M, Ide N, Mizoguchi A, Takai Y (Oct 1999). "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. doi:10.1074/jbc.274.43.30914. PMID 10521485.
• Hartley JL, Temple GF, Brasch MA (Nov 2000). "DNA cloning using in vitro site-specific recombination". Genome Research. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
• 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 (Mar 2001). "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. doi:10.1101/gr.GR1547R. PMC 311072. PMID 11230166.
• Zucconi A, Dente L, Santonico E, Castagnoli L, Cesareni G (Apr 2001). "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. doi:10.1006/jmbi.2001.4572. PMID 11292345.
• Kimura A, Baumann CA, Chiang SH, Saltiel AR (Jul 2001). "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. doi:10.1073/pnas.151252898. PMC 55379. PMID 11481476.
• Xu YC, Wu RF, Gu Y, Yang YS, Yang MC, Nwariaku FE, Terada LS (Aug 2002). "Involvement of TRAF4 in oxidative activation of c-Jun N-terminal kinase". The Journal of Biological Chemistry. 277 (31): 28051–7. doi:10.1074/jbc.M202665200. PMID 12023963.
• Nakayama M, Kikuno R, Ohara O (Nov 2002). "Protein-protein interactions between large proteins: two-hybrid screening using a functionally classified library composed of long cDNAs". Genome Research. 12 (11): 1773–84. doi:10.1101/gr.406902. PMC 187542. PMID 12421765.
• Soubeyran P, Barac A, Szymkiewicz I, Dikic I (Feb 2003). "Cbl-ArgBP2 complex mediates ubiquitination and degradation of c-Abl". The Biochemical Journal. 370 (Pt 1): 29–34. doi:10.1042/BJ20021539. PMC 1223168. PMID 12475393.
• 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". Journal of Cell Science. 117 (Pt 12): 2557–68. doi:10.1242/jcs.01148. PMID 15128873.
• Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP (Aug 2004). "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. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935.
• Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, Bechtel S, Sauermann M, Korf U, Pepperkok R, Sültmann H, Poustka A (Oct 2004). "From ORFeome to biology: a functional genomics pipeline". Genome Research. 14 (10B): 2136–44. doi:10.1101/gr.2576704. PMC 528930. PMID 15489336.