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{{Infobox_gene}}
{{PBB_Controls
'''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]].<ref name="pmid10085297">{{cite journal | vauthors = Mandai K, Nakanishi H, Satoh A, Takahashi K, Satoh K, Nishioka H, Mizoguchi A, Takai Y | title = Ponsin/SH3P12: an l-afadin- and vinculin-binding protein localized at cell-cell and cell-matrix adherens junctions | journal = The Journal of Cell Biology | volume = 144 | issue = 5 | pages = 1001–17 | date = Mar 1999 | pmid = 10085297 | pmc = 2148189 | doi = 10.1083/jcb.144.5.1001 }}</ref><ref name="pmid11001060">{{cite journal | vauthors = Baumann CA, Ribon V, Kanzaki M, Thurmond DC, Mora S, Shigematsu S, Bickel PE, Pessin JE, Saltiel AR | title = CAP defines a second signalling pathway required for insulin-stimulated glucose transport | journal = Nature | volume = 407 | issue = 6801 | pages = 202–7 | date = Sep 2000 | pmid = 11001060 | pmc =  | doi = 10.1038/35025089 | url = https://deepblue.lib.umich.edu/bitstream/2027.42/62940/1/407202a0.pdf }}</ref><ref name="entrez">{{Cite web| title = Entrez Gene: SORBS1 sorbin and SH3 domain containing 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10580| accessdate = }}</ref> CAP/Ponsin is part of a small family of adaptor proteins that regulate [[cell adhesion]], [[growth factor]] signaling and [[cytoskeleton|cytoskeletal]] formation. CAP/Ponsin is mainly expressed in [[cardiac muscle|heart]], [[skeletal muscle]], [[liver]], [[adipose]] tissue, and [[macrophage]]s; in striated muscle tissue, CAP/Ponsin is localized to [[costamere]] structures.
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
==Structure==
{{GNF_Protein_box
CAP/Ponsin may exist as thirteen alternatively-spliced isoforms, ranging from 81 kDa to 142 kDa.<ref name="Lin WH 2001">{{cite journal | vauthors = Lin WH, Huang CJ, Liu MW, Chang HM, Chen YJ, Tai TY, Chuang LM | title = 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 | journal = Genomics | volume = 74 | issue = 1 | pages = 12–20 | date = May 2001 | pmid = 11374898 | doi = 10.1006/geno.2001.6541 }}</ref> CAP/Ponsin is part of an adaptor protein family, of which [[SORBS2|ArgBP2]] and [[SORBS3|vinexin]] are also a part.<ref>{{cite journal | pmid = 11937713 | doi=10.1247/csf.27.1 | volume=27 | title=Vinexin, CAP/ponsin, ArgBP2: a novel adaptor protein family regulating cytoskeletal organization and signal transduction. | date=Feb 2002 | journal=Cell Struct Funct | pages=1–7 | vauthors=Kioka N, Ueda K, Amachi T}}</ref> These proteins contain a conserved sorbin homology (SOHO) domain and three [[SH3 domain]]s, and CAP/Ponsin is expressed in [[cardiac muscle|heart]], [[skeletal muscle]], [[liver]], [[adipose]] tissue, and [[macrophages]].<ref name="Lin WH 2001"/><ref>{{cite journal | vauthors = Ribon V, Printen JA, Hoffman NG, Kay BK, Saltiel AR | title = A novel, multifuntional c-Cbl binding protein in insulin receptor signaling in 3T3-L1 adipocytes | journal = Molecular and Cellular Biology | volume = 18 | issue = 2 | pages = 872–9 | date = Feb 1998 | pmid = 9447983 | doi=10.1128/mcb.18.2.872 | pmc=108798}}</ref><ref name="ReferenceA">{{cite journal | vauthors = Lesniewski LA, Hosch SE, Neels JG, de Luca C, Pashmforoush M, Lumeng CN, Chiang SH, Scadeng M, Saltiel AR, Olefsky JM | title = Bone marrow-specific Cap gene deletion protects against high-fat diet-induced insulin resistance | journal = Nature Medicine | volume = 13 | issue = 4 | pages = 455–62 | date = Apr 2007 | pmid = 17351624 | doi = 10.1038/nm1550 }}</ref>
| image = PBB_Protein_SORBS1_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 2dl3.
| PDB = {{PDB2|2dl3}}
| Name = Sorbin and SH3 domain containing 1
| HGNCid = 14565
| Symbol = SORBS1
| AltSymbols =; CAP; DKFZp451C066; DKFZp586P1422; FLAF2; FLJ12406; KIAA1296; R85FL; SH3D5; SH3P12; SORB1
| OMIM = 605264
| ECnumber =
| Homologene = 83252
| MGIid = 700014
| GeneAtlas_image1 = PBB_GE_SORBS1_211819_s_at_tn.png
| GeneAtlas_image2 = PBB_GE_SORBS1_218087_s_at_tn.png
| GeneAtlas_image3 = PBB_GE_SORBS1_211705_s_at_tn.png
| Function = {{GNF_GO|id=GO:0003779 |text = actin binding}} {{GNF_GO|id=GO:0005158 |text = insulin receptor binding}} {{GNF_GO|id=GO:0019901 |text = protein kinase binding}}
| Component = {{GNF_GO|id=GO:0001725 |text = stress fiber}} {{GNF_GO|id=GO:0005634 |text = nucleus}} {{GNF_GO|id=GO:0005915 |text = zonula adherens}} {{GNF_GO|id=GO:0005924 |text = cell-substrate adherens junction}} {{GNF_GO|id=GO:0016020 |text = membrane}} {{GNF_GO|id=GO:0045121 |text = lipid raft}}  
| Process = {{GNF_GO|id=GO:0006810 |text = transport}} {{GNF_GO|id=GO:0008286 |text = insulin receptor signaling pathway}} {{GNF_GO|id=GO:0015758 |text = glucose transport}} {{GNF_GO|id=GO:0043149 |text = stress fiber formation}} {{GNF_GO|id=GO:0048041 |text = focal adhesion formation}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 10580
    | Hs_Ensembl = ENSG00000095637
    | Hs_RefseqProtein = NP_001030126
    | Hs_RefseqmRNA = NM_001034954
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 10
    | Hs_GenLoc_start = 97061520
    | Hs_GenLoc_end = 97311161
    | Hs_Uniprot = Q9BX66
    | Mm_EntrezGene = 20411
    | Mm_Ensembl = ENSMUSG00000025006
    | Mm_RefseqmRNA = NM_001034962
    | Mm_RefseqProtein = NP_001030134
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 19
    | Mm_GenLoc_start = 40348360
    | Mm_GenLoc_end = 40451928
    | Mm_Uniprot = Q62417
  }}
}}
'''Sorbin and SH3 domain containing 1''', also known as '''SORBS1''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: SORBS1 sorbin and SH3 domain containing 1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10580| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
== Function ==
{{PBB_Summary
In muscle, CAP/Ponsin plays a role in the formation of mature [[costamere]]s from [[focal adhesion]]-like contacts during assembly of the [[sarcomere|contractile apparatus]], as overexpression of CAP/Ponsin disrupted normal cell-matrix contact morphology.<ref name="Gehmlich K 2007">{{cite journal | vauthors = Gehmlich K, Pinotsis N, Hayess K, van der Ven PF, Milting H, El Banayosy A, Körfer R, Wilmanns M, Ehler E, Fürst DO | title = Paxillin and ponsin interact in nascent costameres of muscle cells | journal = Journal of Molecular Biology | volume = 369 | issue = 3 | pages = 665–82 | date = Jun 2007 | pmid = 17462669 | doi = 10.1016/j.jmb.2007.03.050 }}</ref> 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.<ref>{{cite journal | vauthors = Valaperti A, Nishii M, Liu Y, Yang H, Naito K, Liu PP, Eriksson U | title = The adapter protein c-Cbl-associated protein (CAP) protects from acute CVB3-mediated myocarditis through stabilization of type I interferon production and reduced cytotoxicity | journal = Basic Research in Cardiology | volume = 109 | issue = 3 | pages = 411 | date = May 2014 | pmid = 24763933 | doi = 10.1007/s00395-014-0411-3 }}</ref> CAP/Ponsin 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 (gene)|CBL]] to a [[lipid raft]] signaling complex involving [[FLOT1|flotillin]].<ref>{{cite journal | vauthors = Baumann CA, Ribon V, Kanzaki M, Thurmond DC, Mora S, Shigematsu S, Bickel PE, Pessin JE, Saltiel AR | title = CAP defines a second signalling pathway required for insulin-stimulated glucose transport | journal = Nature | volume = 407 | issue = 6801 | pages = 202–7 | date = Sep 2000 | pmid = 11001060 | doi = 10.1038/35025089 }}</ref> A role for CAP/Ponsin in [[macrophage]] function was illuminated by the finding that mice harboring ''SORBS1''-deficient macrophages in [[bone marrow]] was protective against high-fat diet-induced [[insulin resistance]] and showed reduced [[inflammation]].<ref name="ReferenceA"/> In non-muscle cells, CAP/Ponsin inhibits cell spreading and [[focal adhesion]] turnover, as its [[siRNA]]-mediated knockdown resulted in enhanced [[p21-activated kinases|PAK]]/[[Mitogen-activated protein kinase kinase|MEK]]/[[Extracellular signal-regulated kinases|ERK]] activation and cell migration.<ref>{{cite journal | vauthors = Zhang M, Liu J, Cheng A, Deyoung SM, Chen X, Dold LH, Saltiel AR | title = CAP interacts with cytoskeletal proteins and regulates adhesion-mediated ERK activation and motility | journal = The EMBO Journal | volume = 25 | issue = 22 | pages = 5284–93 | date = Nov 2006 | pmid = 17082770 | doi = 10.1038/sj.emboj.7601406 | pmc=1636617}}</ref>
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| summary_text =  
}}


==References==
==Clinical Significance==
{{reflist|2}}
CAP/Ponsin was demonstrated to be down-regulated in end-stage [[heart failure]] patients; an effect that was restored upon mechanical unloading.<ref name="Gehmlich K 2007"/> A [[single nucleotide polymorphism]] in ''SORBS1'' was found to be associated with [[type 2 diabetes]] and [[obesity]].<ref>{{cite journal | vauthors = Lin WH, Chiu KC, Chang HM, Lee KC, Tai TY, Chuang LM | title = 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 | journal = Human Molecular Genetics | volume = 10 | issue = 17 | pages = 1753–60 | date = Aug 2001 | pmid = 11532984 | doi=10.1093/hmg/10.17.1753}}</ref>
==Further reading==
{{refbegin | 2}}
{{PBB_Further_reading
| citations =
*{{cite journal  | author=Kioka N |title=[A novel adaptor protein family regulating cytoskeletal organization and signal transduction--Vinexin, CAP/ponsin, ArgBP2] |journal=Seikagaku |volume=74 |issue= 11 |pages= 1356-60 |year= 2003 |pmid= 12510380 |doi=  }}
*{{cite journal  | author=Ribon V, Herrera R, Kay BK, Saltiel AR |title=A role for CAP, a novel, multifunctional Src homology 3 domain-containing protein in formation of actin stress fibers and focal adhesions. |journal=J. Biol. Chem. |volume=273 |issue= 7 |pages= 4073-80 |year= 1998 |pmid= 9461600 |doi=  }}
*{{cite journal  | author=Mandai K, Nakanishi H, Satoh A, ''et al.'' |title=Ponsin/SH3P12: an l-afadin- and vinculin-binding protein localized at cell-cell and cell-matrix adherens junctions. |journal=J. Cell Biol. |volume=144 |issue= 5 |pages= 1001-17 |year= 1999 |pmid= 10085297 |doi=  }}
*{{cite journal  | author=Asakura T, Nakanishi H, Sakisaka T, ''et al.'' |title=Similar and differential behaviour between the nectin-afadin-ponsin and cadherin-catenin systems during the formation and disruption of the polarized junctional alignment in epithelial cells. |journal=Genes Cells |volume=4 |issue= 10 |pages= 573-81 |year= 2000 |pmid= 10583506 |doi=  }}
*{{cite journal  | author=Nagase T, Kikuno R, Ishikawa KI, ''et al.'' |title=Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro. |journal=DNA Res. |volume=7 |issue= 1 |pages= 65-73 |year= 2000 |pmid= 10718198 |doi=  }}
*{{cite journal  | author=Baumann CA, Ribon V, Kanzaki M, ''et al.'' |title=CAP defines a second signalling pathway required for insulin-stimulated glucose transport. |journal=Nature |volume=407 |issue= 6801 |pages= 202-7 |year= 2000 |pmid= 11001060 |doi= 10.1038/35025089 }}
*{{cite journal  | author=Hartley JL, Temple GF, Brasch MA |title=DNA cloning using in vitro site-specific recombination. |journal=Genome Res. |volume=10 |issue= 11 |pages= 1788-95 |year= 2001 |pmid= 11076863 |doi=  }}
*{{cite journal  | author=Wiemann S, Weil B, Wellenreuther R, ''et al.'' |title=Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs. |journal=Genome Res. |volume=11 |issue= 3 |pages= 422-35 |year= 2001 |pmid= 11230166 |doi= 10.1101/gr.154701 }}
*{{cite journal  | author=Lebre AS, Jamot L, Takahashi J, ''et al.'' |title=Ataxin-7 interacts with a Cbl-associated protein that it recruits into neuronal intranuclear inclusions. |journal=Hum. Mol. Genet. |volume=10 |issue= 11 |pages= 1201-13 |year= 2001 |pmid= 11371513 |doi=  }}
*{{cite journal  | author=Lin WH, Huang CJ, Liu MW, ''et al.'' |title=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. |journal=Genomics |volume=74 |issue= 1 |pages= 12-20 |year= 2001 |pmid= 11374898 |doi= 10.1006/geno.2001.6541 }}
*{{cite journal  | author=Kimura A, Baumann CA, Chiang SH, Saltiel AR |title=The sorbin homology domain: a motif for the targeting of proteins to lipid rafts. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=98 |issue= 16 |pages= 9098-103 |year= 2001 |pmid= 11481476 |doi= 10.1073/pnas.151252898 }}
*{{cite journal | author=Lin WH, Chiu KC, Chang HM, ''et al.'' |title=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. |journal=Hum. Mol. Genet. |volume=10 |issue= 17 |pages= 1753-60 |year= 2002 |pmid= 11532984 |doi=  }}
*{{cite journal  | author=Cowan CA, Henkemeyer M |title=The SH2/SH3 adaptor Grb4 transduces B-ephrin reverse signals. |journal=Nature |volume=413 |issue= 6852 |pages= 174-9 |year= 2001 |pmid= 11557983 |doi= 10.1038/35093123 }}
*{{cite journal  | author=Liu J, Kimura A, Baumann CA, Saltiel AR |title=APS facilitates c-Cbl tyrosine phosphorylation and GLUT4 translocation in response to insulin in 3T3-L1 adipocytes. |journal=Mol. Cell. Biol. |volume=22 |issue= 11 |pages= 3599-609 |year= 2002 |pmid= 11997497 |doi=  }}
*{{cite journal  | author=Xie J, Cai T, Zhang H, ''et al.'' |title=The zinc-finger transcription factor INSM1 is expressed during embryo development and interacts with the Cbl-associated protein. |journal=Genomics |volume=80 |issue= 1 |pages= 54-61 |year= 2003 |pmid= 12079283 |doi=  }}
*{{cite journal  | author=Nakayama M, Kikuno R, Ohara O |title=Protein-protein interactions between large proteins: two-hybrid screening using a functionally classified library composed of long cDNAs. |journal=Genome Res. |volume=12 |issue= 11 |pages= 1773-84 |year= 2003 |pmid= 12421765 |doi= 10.1101/gr.406902 }}
*{{cite journal  | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
*{{cite journal  | author=Vandenbroere I, Paternotte N, Dumont JE, ''et al.'' |title=The c-Cbl-associated protein and c-Cbl are two new partners of the SH2-containing inositol polyphosphate 5-phosphatase SHIP2. |journal=Biochem. Biophys. Res. Commun. |volume=300 |issue= 2 |pages= 494-500 |year= 2003 |pmid= 12504111 |doi=  }}
*{{cite journal  | author=Yang WS, Lee WJ, Huang KC, ''et al.'' |title=mRNA levels of the insulin-signaling molecule SORBS1 in the adipose depots of nondiabetic women. |journal=Obes. Res. |volume=11 |issue= 4 |pages= 586-90 |year= 2003 |pmid= 12690089 |doi=  }}
}}
{{refend}}


{{protein-stub}}
== Interactions ==
{{WikiDoc Sources}}
 
SORBS1 has been shown to [[Protein-protein interaction|interact]] with:
{{div col|colwidth=20em}}
* [[Cbl gene|CBL]],<ref name = pmid15128873/><ref name = pmid12504111>{{cite journal | vauthors = Vandenbroere I, Paternotte N, Dumont JE, Erneux C, Pirson I | title = The c-Cbl-associated protein and c-Cbl are two new partners of the SH2-containing inositol polyphosphate 5-phosphatase SHIP2 | journal = Biochemical and Biophysical Research Communications | volume = 300 | issue = 2 | pages = 494–500 | date = Jan 2003 | pmid = 12504111 | doi =  10.1016/s0006-291x(02)02894-2}}</ref>
* [[FLOT1]],<ref name = pmid11001060 /><ref name = pmid15128873>{{cite journal | vauthors = Haglund K, Ivankovic-Dikic I, Shimokawa N, Kruh GD, Dikic I | title = Recruitment of Pyk2 and Cbl to lipid rafts mediates signals important for actin reorganization in growing neurites | journal = Journal of Cell Science | volume = 117 | issue = Pt 12 | pages = 2557–68 | date = May 2004 | pmid = 15128873 | doi = 10.1242/jcs.01148 }}</ref><ref name = pmid11481476>{{cite journal | vauthors = Kimura A, Baumann CA, Chiang SH, Saltiel AR | title = The sorbin homology domain: a motif for the targeting of proteins to lipid rafts | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 98 | issue = 16 | pages = 9098–103 | date = Jul 2001 | pmid = 11481476 | pmc = 55379 | doi = 10.1073/pnas.151252898 }}</ref>
* [[INPPL1]],<ref name = pmid12504111/>
* [[INSM1]],<ref name = pmid12079283>{{cite journal | vauthors = Xie J, Cai T, Zhang H, Lan MS, Notkins AL | title = The zinc-finger transcription factor INSM1 is expressed during embryo development and interacts with the Cbl-associated protein | journal = Genomics | volume = 80 | issue = 1 | pages = 54–61 | date = Jul 2002 | pmid = 12079283 | pmc = 1237014 | doi =  10.1006/geno.2002.6800}}</ref>
* [[MLLT4]],<ref name = pmid10085297/>
* [[PXN]],<ref name="Gehmlich K 2007"/> and
* [[Vinculin]].<ref name = pmid10085297 />
{{Div col end}}
{{Clear}}
 
== References ==
{{Reflist|33em}}
 
== Further reading ==
{{Refbegin|33em}}
* {{cite journal | vauthors = Kioka N | title = [A novel adaptor protein family regulating cytoskeletal organization and signal transduction--Vinexin, CAP/ponsin, ArgBP2] | journal = Seikagaku. The Journal of Japanese Biochemical Society | volume = 74 | issue = 11 | pages = 1356–60 | date = Nov 2002 | pmid = 12510380 | doi =  }}
* {{cite journal | vauthors = Ribon V, Herrera R, Kay BK, Saltiel AR | title = A role for CAP, a novel, multifunctional Src homology 3 domain-containing protein in formation of actin stress fibers and focal adhesions | journal = The Journal of Biological Chemistry | volume = 273 | issue = 7 | pages = 4073–80 | date = Feb 1998 | pmid = 9461600 | doi = 10.1074/jbc.273.7.4073 }}
* {{cite journal | vauthors = Asakura T, Nakanishi H, Sakisaka T, Takahashi K, Mandai K, Nishimura M, Sasaki T, Takai Y | title = Similar and differential behaviour between the nectin-afadin-ponsin and cadherin-catenin systems during the formation and disruption of the polarized junctional alignment in epithelial cells | journal = Genes to Cells | volume = 4 | issue = 10 | pages = 573–81 | date = Oct 1999 | pmid = 10583506 | doi = 10.1046/j.1365-2443.1999.00283.x }}
* {{cite journal | vauthors = Nagase T, Kikuno R, Ishikawa KI, Hirosawa M, Ohara O | title = Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro | journal = DNA Research | volume = 7 | issue = 1 | pages = 65–73 | date = Feb 2000 | pmid = 10718198 | doi = 10.1093/dnares/7.1.65 }}
* {{cite journal | vauthors = Hartley JL, Temple GF, Brasch MA | title = DNA cloning using in vitro site-specific recombination | journal = Genome Research | volume = 10 | issue = 11 | pages = 1788–95 | date = Nov 2000 | pmid = 11076863 | pmc = 310948 | doi = 10.1101/gr.143000 }}
* {{cite journal | vauthors = Lebre AS, Jamot L, Takahashi J, Spassky N, Leprince C, Ravisé N, Zander C, Fujigasaki H, Kussel-Andermann P, Duyckaerts C, Camonis JH, Brice A | title = Ataxin-7 interacts with a Cbl-associated protein that it recruits into neuronal intranuclear inclusions | journal = Human Molecular Genetics | volume = 10 | issue = 11 | pages = 1201–13 | date = May 2001 | pmid = 11371513 | doi = 10.1093/hmg/10.11.1201 }}
* {{cite journal | vauthors = Lin WH, Huang CJ, Liu MW, Chang HM, Chen YJ, Tai TY, Chuang LM | title = 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 | journal = Genomics | volume = 74 | issue = 1 | pages = 12–20 | date = May 2001 | pmid = 11374898 | doi = 10.1006/geno.2001.6541 }}
* {{cite journal | vauthors = Kimura A, Baumann CA, Chiang SH, Saltiel AR | title = The sorbin homology domain: a motif for the targeting of proteins to lipid rafts | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 98 | issue = 16 | pages = 9098–103 | date = Jul 2001 | pmid = 11481476 | pmc = 55379 | doi = 10.1073/pnas.151252898 }}
* {{cite journal | vauthors = Lin WH, Chiu KC, Chang HM, Lee KC, Tai TY, Chuang LM | title = 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 | journal = Human Molecular Genetics | volume = 10 | issue = 17 | pages = 1753–60 | date = Aug 2001 | pmid = 11532984 | doi = 10.1093/hmg/10.17.1753 }}
* {{cite journal | vauthors = Cowan CA, Henkemeyer M | title = The SH2/SH3 adaptor Grb4 transduces B-ephrin reverse signals | journal = Nature | volume = 413 | issue = 6852 | pages = 174–9 | date = Sep 2001 | pmid = 11557983 | doi = 10.1038/35093123 }}
* {{cite journal | vauthors = Liu J, Kimura A, Baumann CA, Saltiel AR | title = APS facilitates c-Cbl tyrosine phosphorylation and GLUT4 translocation in response to insulin in 3T3-L1 adipocytes | journal = Molecular and Cellular Biology | volume = 22 | issue = 11 | pages = 3599–609 | date = Jun 2002 | pmid = 11997497 | pmc = 133825 | doi = 10.1128/MCB.22.11.3599-3609.2002 }}
* {{cite journal | vauthors = Xie J, Cai T, Zhang H, Lan MS, Notkins AL | title = The zinc-finger transcription factor INSM1 is expressed during embryo development and interacts with the Cbl-associated protein | journal = Genomics | volume = 80 | issue = 1 | pages = 54–61 | date = Jul 2002 | pmid = 12079283 | pmc = 1237014 | doi = 10.1006/geno.2002.6800 }}
* {{cite journal | vauthors = Nakayama M, Kikuno R, Ohara O | title = Protein-protein interactions between large proteins: two-hybrid screening using a functionally classified library composed of long cDNAs | journal = Genome Research | volume = 12 | issue = 11 | pages = 1773–84 | date = Nov 2002 | pmid = 12421765 | pmc = 187542 | doi = 10.1101/gr.406902 }}
* {{cite journal | vauthors = Vandenbroere I, Paternotte N, Dumont JE, Erneux C, Pirson I | title = The c-Cbl-associated protein and c-Cbl are two new partners of the SH2-containing inositol polyphosphate 5-phosphatase SHIP2 | journal = Biochemical and Biophysical Research Communications | volume = 300 | issue = 2 | pages = 494–500 | date = Jan 2003 | pmid = 12504111 | doi = 10.1016/S0006-291X(02)02894-2 }}
* {{cite journal | vauthors = Yang WS, Lee WJ, Huang KC, Lee KC, Chao CL, Chen CL, Tai TY, Chuang LM | title = mRNA levels of the insulin-signaling molecule SORBS1 in the adipose depots of nondiabetic women | journal = Obesity Research | volume = 11 | issue = 4 | pages = 586–90 | date = Apr 2003 | pmid = 12690089 | doi = 10.1038/oby.2003.82 }}
{{Refend}}
 
{{PDB Gallery|geneid=10580}}

Latest revision as of 12:49, 4 November 2018

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

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.[1][2][3] CAP/Ponsin is part of a small family of adaptor proteins that regulate cell adhesion, growth factor signaling and cytoskeletal formation. CAP/Ponsin is mainly expressed in heart, skeletal muscle, liver, adipose tissue, and macrophages; in striated muscle tissue, CAP/Ponsin is localized to costamere structures.

Structure

CAP/Ponsin may exist as thirteen alternatively-spliced isoforms, ranging from 81 kDa to 142 kDa.[4] CAP/Ponsin is part of an adaptor protein family, of which ArgBP2 and vinexin are also a part.[5] 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.[4][6][7]

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.[8] 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.[9] CAP/Ponsin 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.[10] A role for CAP/Ponsin in macrophage function was illuminated by the finding that mice harboring SORBS1-deficient macrophages in bone marrow was protective against high-fat diet-induced insulin resistance and showed reduced inflammation.[7] In non-muscle cells, CAP/Ponsin inhibits cell spreading and focal adhesion turnover, as its siRNA-mediated knockdown resulted in enhanced PAK/MEK/ERK activation and cell migration.[11]

Clinical Significance

CAP/Ponsin was demonstrated to be down-regulated in end-stage heart failure patients; an effect that was restored upon mechanical unloading.[8] A single nucleotide polymorphism in SORBS1 was found to be associated with type 2 diabetes and obesity.[12]

Interactions

SORBS1 has been shown to interact with:

References

  1. ↑ 1.0 1.1 1.2 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.
  2. ↑ 2.0 2.1 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. doi:10.1038/35025089. PMID 11001060.
  3. ↑ "Entrez Gene: SORBS1 sorbin and SH3 domain containing 1".
  4. ↑ 4.0 4.1 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". Genomics. 74 (1): 12–20. doi:10.1006/geno.2001.6541. PMID 11374898.
  5. ↑ 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: 1–7. doi:10.1247/csf.27.1. PMID 11937713.
  6. ↑ 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.
  7. ↑ 7.0 7.1 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.
  8. ↑ 8.0 8.1 8.2 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.
  9. ↑ 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". Basic Research in Cardiology. 109 (3): 411. doi:10.1007/s00395-014-0411-3. PMID 24763933.
  10. ↑ 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". Nature. 407 (6801): 202–7. doi:10.1038/35025089. PMID 11001060.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ 13.0 13.1 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.
  14. ↑ 14.0 14.1 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.
  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". 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.
  16. ↑ 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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