SORBS2

Last updated
SORBS2
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases SORBS2 , ARGBP2, PRO0618, sorbin and SH3 domain containing 2
External IDs OMIM: 616349 MGI: 1924574 HomoloGene: 83295 GeneCards: SORBS2
Orthologs
SpeciesHumanMouse
Entrez

8470

234214

Ensembl

ENSG00000154556

ENSMUSG00000031626

UniProt

O94875

Q3UTJ2

RefSeq (mRNA)

NM_001205219
NM_172752
NM_001310707
NM_001310708

RefSeq (protein)
Location (UCSC) Chr 4: 185.59 – 185.96 Mb Chr 8: 45.96 – 46.28 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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.

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 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. [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:

Related Research Articles

<span class="mw-page-title-main">SH3 domain</span> Small protein domain found in some kinases and GTPases

The SRC Homology 3 Domain is a small protein domain of about 60 amino acid residues. Initially, SH3 was described as a conserved sequence in the viral adaptor protein v-Crk. This domain is also present in the molecules of phospholipase and several cytoplasmic tyrosine kinases such as Abl and Src. It has also been identified in several other protein families such as: PI3 Kinase, Ras GTPase-activating protein, CDC24 and cdc25. SH3 domains are found in proteins of signaling pathways regulating the cytoskeleton, the Ras protein, and the Src kinase and many others. The SH3 proteins interact with adaptor proteins and tyrosine kinases. Interacting with tyrosine kinases, SH3 proteins usually bind far away from the active site. Approximately 300 SH3 domains are found in proteins encoded in the human genome. In addition to that, the SH3 domain was responsible for controlling protein-protein interactions in the signal transduction pathways and regulating the interactions of proteins involved in the cytoplasmic signaling.

<span class="mw-page-title-main">ABL (gene)</span> Human protein-coding gene on chromosome 9

Tyrosine-protein kinase ABL1 also known as ABL1 is a protein that, in humans, is encoded by the ABL1 gene located on chromosome 9. c-Abl is sometimes used to refer to the version of the gene found within the mammalian genome, while v-Abl refers to the viral gene, which was initially isolated from the Abelson murine leukemia virus.

<span class="mw-page-title-main">GRB2</span> Protein-coding gene in the species Homo sapiens

Growth factor receptor-bound protein 2, also known as Grb2, is an adaptor protein involved in signal transduction/cell communication. In humans, the GRB2 protein is encoded by the GRB2 gene.

<span class="mw-page-title-main">Paxillin</span> Protein-coding gene in the species Homo sapiens

Paxillin is a protein that in humans is encoded by the PXN gene. Paxillin is expressed at focal adhesions of non-striated cells and at costameres of striated muscle cells, and it functions to adhere cells to the extracellular matrix. Mutations in PXN as well as abnormal expression of paxillin protein has been implicated in the progression of various cancers.

<span class="mw-page-title-main">Adapter molecule crk</span> Protein-coding gene in the species Homo sapiens

Adapter molecule crk also known as proto-oncogene c-Crk is a protein that in humans is encoded by the CRK gene.

<span class="mw-page-title-main">CBL (gene)</span> Mammalian gene

Cbl is a mammalian gene family. CBL gene, a part of the Cbl family, encodes the protein CBL which is an E3 ubiquitin-protein ligase involved in cell signalling and protein ubiquitination. Mutations to this gene have been implicated in a number of human cancers, particularly acute myeloid leukaemia.

<span class="mw-page-title-main">PLCG1</span> Protein-coding gene in the species Homo sapiens

Phospholipase C, gamma 1, also known as PLCG1 and PLCgamma1, is a protein that in humans involved in cell growth, migration, apoptosis, and proliferation. It is encoded by the PLCG1 gene and is part of the PLC superfamily.

<span class="mw-page-title-main">RAS p21 protein activator 1</span> Protein-coding gene in the species Homo sapiens

RAS p21 protein activator 1 or RasGAP, also known as RASA1, is a 120-kDa cytosolic human protein that provides two principal activities:

<span class="mw-page-title-main">CRKL</span> Protein-coding gene in the species Homo sapiens

Crk-like protein is a protein that in humans is encoded by the CRKL gene.

<span class="mw-page-title-main">SH3KBP1</span> Protein-coding gene in the species Homo sapiens

SH3 domain-containing kinase-binding protein 1 is an adaptor protein that in humans is encoded by the SH3KBP1 gene.

<span class="mw-page-title-main">PTK2B</span> Protein-coding gene in the species Homo sapiens

Protein tyrosine kinase 2 beta is an enzyme that in humans is encoded by the PTK2B gene.

<span class="mw-page-title-main">NCK1</span> Protein-coding gene in the species Homo sapiens

Cytoplasmic protein NCK1 is a protein that in humans is encoded by the NCK1 gene.

<span class="mw-page-title-main">BCAR1</span> Protein-coding gene in the species Homo sapiens

Breast cancer anti-estrogen resistance protein 1 is a protein that in humans is encoded by the BCAR1 gene.

<span class="mw-page-title-main">ABL2</span> Protein-coding gene in the species Homo sapiens

Tyrosine-protein kinase ABL2 also known as Abelson-related gene (Arg) is an enzyme that in humans is encoded by the ABL2 gene.

<span class="mw-page-title-main">FLOT1</span> Protein-coding gene in the species Homo sapiens

Flotillin-1 is a protein that in humans is encoded by the FLOT1 gene.

<span class="mw-page-title-main">SORBS1</span> Protein-coding gene in the species Homo sapiens

CAP/Ponsin protein, also known as Sorbin and SH3 domain-containing protein 1 is a protein that in humans is encoded by the SORBS1 gene. It is part of a small family of adaptor proteins that regulate cell adhesion, growth factor signaling and cytoskeletal formation. It is mainly expressed in heart, skeletal muscle, liver, adipose tissue, and macrophages; in striated muscle tissue, it is localized to costamere structures.

<span class="mw-page-title-main">CD2AP</span> Protein

CD2-associated protein is a protein that in humans is encoded by the CD2AP gene.

<span class="mw-page-title-main">NCK2</span> Protein-coding gene in the species Homo sapiens

Cytoplasmic protein NCK2 is a protein that in humans is encoded by the NCK2 gene.

<span class="mw-page-title-main">SORBS3</span> Protein-coding gene in the species Homo sapiens

Vinexin is a protein that in humans is encoded by the SORBS3 gene.

A non-receptor tyrosine kinase (nRTK) is a cytosolic enzyme that is responsible for catalysing the transfer of a phosphate group from a nucleoside triphosphate donor, such as ATP, to tyrosine residues in proteins. Non-receptor tyrosine kinases are a subgroup of protein family tyrosine kinases, enzymes that can transfer the phosphate group from ATP to a tyrosine residue of a protein (phosphorylation). These enzymes regulate many cellular functions by switching on or switching off other enzymes in a cell.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000154556 - Ensembl, May 2017
  2. 1 2 3 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. 1 2 3 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 . hdl: 20.500.12613/9174 . PMID   9211900.
  6. 1 2 "Entrez Gene: SORBS2 sorbin and SH3 domain containing 2".
  7. 1 2 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. 1 2 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 . hdl: 20.500.12613/9174 . 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. Bibcode:2001PNAS...98.9098K. 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. S2CID   7420385.
  13. 1 2 3 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. S2CID   205310317.
  17. 1 2 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. 1 2 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. Bibcode:2001PNAS...98.9098K. 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.

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