SORBS1

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.[5][6][7] 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.

SORBS1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesSORBS1, CAP, FLAF2, R85FL, SH3D5, SH3P12, SORB1, sorbin and SH3 domain containing 1
External IDsOMIM: 605264 MGI: 700014 HomoloGene: 83252 GeneCards: SORBS1
Orthologs
SpeciesHumanMouse
Entrez

10580

20411

Ensembl

ENSG00000095637

ENSMUSG00000025006

UniProt

Q9BX66

Q62417

RefSeq (mRNA)

NM_001034962
NM_001034963
NM_001034964
NM_009166
NM_178362

RefSeq (protein)
Location (UCSC)Chr 10: 95.31 – 95.56 MbChr 19: 40.29 – 40.51 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Structure

CAP/Ponsin may exist as thirteen alternatively-spliced isoforms, ranging from 81 kDa to 142 kDa.[8] It is part of an adaptor protein family, of which ArgBP2 and vinexin are also a part.[9] These proteins contain a conserved sorbin homology (SOHO) domain and three SH3 domains, and CAP/Ponsin is expressed in heart, skeletal muscle, liver, adipose tissue, and macrophages.[8][10][11]

Function

In muscle, CAP/Ponsin plays a role in the formation of mature costameres from focal adhesion-like contacts during assembly of the contractile apparatus, as overexpression of CAP/Ponsin disrupted normal cell-matrix contact morphology.[12] In a mouse model of viral myocarditis due to Coxsackievirus infection, CAP/Ponsin stabilized antiviral type I interferon production and was protective against apoptosis and cytotoxicity.[13] It has also been shown to be a major regulator of insulin-stimulated signaling and regulation of glucose uptake, by potentiating insulin-induced phosphorylation and recruitment of CBL to a lipid raft signaling complex involving flotillin.[14] A role for it in macrophage function was illuminated by the finding that, in mice harboring SORBS1-deficient macrophages in bone marrow, it was protective against high-fat diet-induced insulin resistance and showed reduced inflammation.[11] In non-muscle cells, it inhibits cell spreading and focal adhesion turnover, as its siRNA-mediated knockdown resulted in enhanced PAK/MEK/ERK activation and cell migration.[15]

Clinical Significance

CAP/Ponsin was demonstrated to be down-regulated in end-stage heart failure patients; an effect that was restored upon mechanical unloading.[12] A single nucleotide polymorphism in SORBS1 was found to be associated with type 2 diabetes and obesity.[16]

Interactions

SORBS1 has been shown to interact with:

References
  1. GRCh38: Ensembl release 89: ENSG00000095637 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000025006 - 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. Mandai K, Nakanishi H, Satoh A, Takahashi K, Satoh K, Nishioka H, Mizoguchi A, Takai Y (Mar 1999). "Ponsin/SH3P12: an l-afadin- and vinculin-binding protein localized at cell-cell and cell-matrix adherens junctions". The Journal of Cell Biology. 144 (5): 1001–17. doi:10.1083/jcb.144.5.1001. PMC 2148189. PMID 10085297.
  6. Baumann CA, Ribon V, Kanzaki M, Thurmond DC, Mora S, Shigematsu S, Bickel PE, Pessin JE, Saltiel AR (Sep 2000). "CAP defines a second signalling pathway required for insulin-stimulated glucose transport" (PDF). Nature. 407 (6801): 202–7. Bibcode:2000Natur.407..202B. doi:10.1038/35025089. hdl:2027.42/62940. PMID 11001060. S2CID 4334519.
  7. "Entrez Gene: SORBS1 sorbin and SH3 domain containing 1".
  8. Lin WH, Huang CJ, Liu MW, Chang HM, Chen YJ, Tai TY, Chuang LM (May 2001). "Cloning, mapping, and characterization of the human sorbin and SH3 domain containing 1 (SORBS1) gene: a protein associated with c-Abl during insulin signaling in the hepatoma cell line Hep3B" (PDF). Genomics. 74 (1): 12–20. doi:10.1006/geno.2001.6541. PMID 11374898.
  9. 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.
  10. Ribon V, Printen JA, Hoffman NG, Kay BK, Saltiel AR (Feb 1998). "A novel, multifuntional c-Cbl binding protein in insulin receptor signaling in 3T3-L1 adipocytes". Molecular and Cellular Biology. 18 (2): 872–9. doi:10.1128/mcb.18.2.872. PMC 108798. PMID 9447983.
  11. Lesniewski LA, Hosch SE, Neels JG, de Luca C, Pashmforoush M, Lumeng CN, Chiang SH, Scadeng M, Saltiel AR, Olefsky JM (Apr 2007). "Bone marrow-specific Cap gene deletion protects against high-fat diet-induced insulin resistance". Nature Medicine. 13 (4): 455–62. doi:10.1038/nm1550. PMID 17351624. S2CID 22210202.
  12. Gehmlich K, Pinotsis N, Hayess K, van der Ven PF, Milting H, El Banayosy A, Körfer R, Wilmanns M, Ehler E, Fürst DO (Jun 2007). "Paxillin and ponsin interact in nascent costameres of muscle cells". Journal of Molecular Biology. 369 (3): 665–82. doi:10.1016/j.jmb.2007.03.050. PMID 17462669.
  13. Valaperti A, Nishii M, Liu Y, Yang H, Naito K, Liu PP, Eriksson U (May 2014). "The adapter protein c-Cbl-associated protein (CAP) protects from acute CVB3-mediated myocarditis through stabilization of type I interferon production and reduced cytotoxicity" (PDF). Basic Research in Cardiology. 109 (3): 411. doi:10.1007/s00395-014-0411-3. PMID 24763933. S2CID 23062795.
  14. Baumann CA, Ribon V, Kanzaki M, Thurmond DC, Mora S, Shigematsu S, Bickel PE, Pessin JE, Saltiel AR (Sep 2000). "CAP defines a second signalling pathway required for insulin-stimulated glucose transport" (PDF). Nature. 407 (6801): 202–7. Bibcode:2000Natur.407..202B. doi:10.1038/35025089. hdl:2027.42/62940. PMID 11001060. S2CID 4334519.
  15. Zhang M, Liu J, Cheng A, Deyoung SM, Chen X, Dold LH, Saltiel AR (Nov 2006). "CAP interacts with cytoskeletal proteins and regulates adhesion-mediated ERK activation and motility". The EMBO Journal. 25 (22): 5284–93. doi:10.1038/sj.emboj.7601406. PMC 1636617. PMID 17082770.
  16. Lin WH, Chiu KC, Chang HM, Lee KC, Tai TY, Chuang LM (Aug 2001). "Molecular scanning of the human sorbin and SH3-domain-containing-1 (SORBS1) gene: positive association of the T228A polymorphism with obesity and type 2 diabetes". Human Molecular Genetics. 10 (17): 1753–60. doi:10.1093/hmg/10.17.1753. PMID 11532984.
  17. 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.
  18. Vandenbroere I, Paternotte N, Dumont JE, Erneux C, Pirson I (Jan 2003). "The c-Cbl-associated protein and c-Cbl are two new partners of the SH2-containing inositol polyphosphate 5-phosphatase SHIP2". Biochemical and Biophysical Research Communications. 300 (2): 494–500. doi:10.1016/s0006-291x(02)02894-2. PMID 12504111.
  19. 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.
  20. Xie J, Cai T, Zhang H, Lan MS, Notkins AL (Jul 2002). "The zinc-finger transcription factor INSM1 is expressed during embryo development and interacts with the Cbl-associated protein". Genomics. 80 (1): 54–61. doi:10.1006/geno.2002.6800. PMC 1237014. PMID 12079283.

Further reading
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