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{{Short description|Protein-coding gene in the species Homo sapiens}}
{{PBB|geneid=9531}}
{{cs1 config|name-list-style=vanc}}{{Infobox_gene}}
'''BAG family molecular chaperone regulator 3''' is a [[protein]] that in humans is encoded by the ''BAG3'' [[gene]]. BAG3 is involved in [[chaperone-assisted selective autophagy (CASA)]].<ref name="pmid9873016">{{cite journal | author = Takayama S, Xie Z, Reed JC | title = An evolutionarily conserved family of Hsp70/Hsc70 molecular chaperone regulators | journal = J Biol Chem | volume = 274 | issue = 2 | pages = 781–6 |date=February 1999 | pmid = 9873016 | pmc = | doi =10.1074/jbc.274.2.781 }}</ref><ref name="pmid18094623">{{cite journal | author = Carra S, Seguin SJ, Landry J | title = HspB8 and Bag3: a new chaperone complex targeting misfolded proteins to macroautophagy | journal = Autophagy | volume = 4 | issue = 2 | pages = 237–9 |date=January 2008 | pmid = 18094623 | pmc = | doi = }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: BAG3 BCL2-associated athanogene 3| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9531| accessdate = }}</ref><ref name="pmid20060297">{{cite journal | author = Arndt V, Dick N, Tawo R, Dreiseidler M, Wenzel D, Hesse M, Fürst DO, Saftig P, Saint R, Fleischmann BK, Hoch M, Höhfeld J | title = Chaperone-assisted selective autophagy is essential for muscle maintenance | journal = Curr Biol | volume = 20 | issue = 2 | pages = 143–8 |date=January 2010 | pmid = 20060297 | pmc = | doi = 10.1016/j.cub.2009.11.022 }}</ref><ref name="pmid23434281">{{cite journal | author = Ulbricht A, Eppler FJ, Tapia VE, van der Ven PF, Hampe N, Hersch N, Vakeel P, Stadel D, Haas A, Saftig P, Behrends C, Fürst DO, Volkmer R, Hoffmann B, Kolanus W, Höhfeld J. | title = Cellular Mechanotransduction Relies on Tension-Induced and Chaperone-Assisted Autophagy | journal = Curr Biol | volume = 23 | issue = 5 | pages = 430–5 |date=February 2013 | pmid = 23434281 | pmc = | doi = 10.1016/j.cub.2013.01.064 }}</ref>
'''BAG family molecular chaperone regulator 3''' is a [[protein]] that in humans is encoded by the ''BAG3'' [[gene]]. BAG3 is involved in [[chaperone-assisted selective autophagy]].<ref name="pmid9873016">{{cite journal | vauthors = Takayama S, Xie Z, Reed JC | title = An evolutionarily conserved family of Hsp70/Hsc70 molecular chaperone regulators | journal = The Journal of Biological Chemistry | volume = 274 | issue = 2 | pages = 781–6 | date = Jan 1999 | pmid = 9873016 | doi = 10.1074/jbc.274.2.781 | doi-access = free }}</ref><ref name="pmid18094623">{{cite journal | vauthors = Carra S, Seguin SJ, Landry J | title = HspB8 and Bag3: a new chaperone complex targeting misfolded proteins to macroautophagy | journal = Autophagy | volume = 4 | issue = 2 | pages = 237–9 | date = Feb 2008 | pmid = 18094623 | doi = 10.4161/auto.5407 | doi-access = free }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: BAG3 BCL2-associated athanogene 3| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9531}}</ref><ref name="pmid20060297">{{cite journal | vauthors = Arndt V, Dick N, Tawo R, Dreiseidler M, Wenzel D, Hesse M, Fürst DO, Saftig P, Saint R, Fleischmann BK, Hoch M, Höhfeld J | title = Chaperone-assisted selective autophagy is essential for muscle maintenance | journal = Current Biology | volume = 20 | issue = 2 | pages = 143–8 | date = Jan 2010 | pmid = 20060297 | doi = 10.1016/j.cub.2009.11.022 | s2cid = 8885338 | doi-access = free }}</ref><ref name="pmid23434281">{{cite journal | vauthors = Ulbricht A, Eppler FJ, Tapia VE, van der Ven PF, Hampe N, Hersch N, Vakeel P, Stadel D, Haas A, Saftig P, Behrends C, Fürst DO, Volkmer R, Hoffmann B, Kolanus W, Höhfeld J | title = Cellular mechanotransduction relies on tension-induced and chaperone-assisted autophagy | journal = Current Biology | volume = 23 | issue = 5 | pages = 430–5 | date = Mar 2013 | pmid = 23434281 | doi = 10.1016/j.cub.2013.01.064 | doi-access = free }}</ref>


== Function ==
== Function ==
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== Clinical significance ==
== Clinical significance ==


BAG gene has been implicated in age related neurodegenerative diseases such as [[Alzheimer]]'s. It has been demonstrated that BAG1 and BAG 3 regulate the proteasomal and lysosomal protein elimination pathways, respectively.<ref>[http://www.nature.com/emboj/journal/v28/n7/full/emboj200929a.html Gamerdinger M, Hajieva P, Kaya AM, Wolfrum U, Hartl FU, Behl C. 2009" ''EMBO J'' 28(7) 889-901.] Protein quality control during aging involves recruitment of the macroautophagy pathway by BAG3</ref><ref>[http://www.physorg.com/news155141336.html Physorg:Old Cells Work Differently]</ref> It has also been shown to be the cause of familial dilated cardiomyopathy.<ref name=pmid21353195>{{cite journal|last=Norton|first=N|coauthors=Li, D, Rieder, MJ, Siegfried, JD, Rampersaud, E, Züchner, S, Mangos, S, Gonzalez-Quintana, J, Wang, L, McGee, S, Reiser, J, Martin, E, Nickerson, DA, Hershberger, RE|title=Genome-wide studies of copy number variation and exome sequencing identify rare variants in BAG3 as a cause of dilated cardiomyopathy.|journal=American Journal of Human Genetics|date=Mar 11, 2011|volume=88|issue=3|pages=273–82|pmid=21353195|doi=10.1016/j.ajhg.2011.01.016|pmc=3059419}}</ref>
BAG gene has been implicated in age related neurodegenerative diseases such as [[Alzheimer]]'s. It has been demonstrated that BAG1 and BAG3 regulate the proteasomal and lysosomal protein elimination pathways, respectively.<ref>[http://www.nature.com/emboj/journal/v28/n7/full/emboj200929a.html Gamerdinger M, Hajieva P, Kaya AM, Wolfrum U, Hartl FU, Behl C. 2009" ''EMBO J'' 28(7) 889-901.] Protein quality control during aging involves recruitment of the macroautophagy pathway by BAG3</ref><ref>[http://www.physorg.com/news155141336.html Physorg:Old Cells Work Differently]</ref> It has also been shown to be a cause of familial dilated cardiomyopathy.<ref name=pmid21353195>{{cite journal | vauthors = Norton N, Li D, Rieder MJ, Siegfried JD, Rampersaud E, Züchner S, Mangos S, Gonzalez-Quintana J, Wang L, McGee S, Reiser J, Martin E, Nickerson DA, Hershberger RE | title = Genome-wide studies of copy number variation and exome sequencing identify rare variants in BAG3 as a cause of dilated cardiomyopathy | journal = American Journal of Human Genetics | volume = 88 | issue = 3 | pages = 273–82 | date = Mar 2011 | pmid = 21353195 | pmc = 3059419 | doi = 10.1016/j.ajhg.2011.01.016 }}</ref>
That BAG3 mutations are responsible for familial dilated cardiomyopathy is confirmed by another study describing 6 new molecular variants (2 missense and 4 premature Stops
That BAG3 mutations are responsible for familial dilated cardiomyopathy is confirmed by another study describing 6 new molecular variants (2 missense and 4 premature Stops
). Moreover, the same publication reported that BAG3 polymorphisms are also associated with sporadic forms of the disease together with HSPB7 locus.<ref name=pmid21459883>{{cite journal|last=Villard|first=E|coauthors=Perret, C, Gary, F, Proust, C, Dilanian, G, Hengstenberg, C, Ruppert, V, Arbustini, E, Wichter, T, Germain, M, Dubourg, O, Tavazzi, L, Aumont, MC, DeGroote, P, Fauchier, L, Trochu, JN, Gibelin, P, Aupetit, JF, Stark, K, Erdmann, J, Hetzer, R, Roberts, AM, Barton, PJ, Regitz-Zagrosek, V; Cardiogenics Consortium, Aslam, U, Duboscq-Bidot, L, Meyborg, M, Maisch, B, Madeira, H, Waldenström, A, Galve, E, Cleland, JG, Dorent, R, Roizes, G, Zeller, T, Blankenberg, S, Goodall, AH, Cook, S, Tregouet, DA, Tiret, L, Isnard, R, Komajda, M, Charron, P, Cambien, F|title=A genome-wide association study identifies two loci associated with heart failure due to dilated cardiomyopathy|date=April 1, 2011|volume=32|issue=9|pages=1065–76|pmid=21459883|doi=10.1093/eurheartj/ehr105}}</ref>
). Moreover, the same publication reported that BAG3 polymorphisms are also associated with sporadic forms of the disease together with HSPB7 locus.<ref name=pmid21459883>{{cite journal | vauthors = Villard E, Perret C, Gary F, Proust C, Dilanian G, Hengstenberg C, Ruppert V, Arbustini E, Wichter T, Germain M, Dubourg O, Tavazzi L, Aumont MC, DeGroote P, Fauchier L, Trochu JN, Gibelin P, Aupetit JF, Stark K, Erdmann J, Hetzer R, Roberts AM, Barton PJ, Regitz-Zagrosek V, Aslam U, Duboscq-Bidot L, Meyborg M, Maisch B, Madeira H, Waldenström A, Galve E, Cleland JG, Dorent R, Roizes G, Zeller T, Blankenberg S, Goodall AH, Cook S, Tregouet DA, Tiret L, Isnard R, Komajda M, Charron P, Cambien F | title = A genome-wide association study identifies two loci associated with heart failure due to dilated cardiomyopathy | journal = European Heart Journal | volume = 32 | issue = 9 | pages = 1065–76 | date = May 2011 | pmid = 21459883 | pmc = 3086901 | doi = 10.1093/eurheartj/ehr105 }}</ref>


In muscle cells, BAG3 cooperates with the molecular chaperones Hsc70 and HspB8 to induce the degradation of mechanically damaged cytoskeleton components in lysosomes. This process is called [[chaperone-assisted selective autophagy (CASA)]] and is essential for maintaining muscle activity in flies, mice and men.<ref name="pmid20060297" />
In muscle cells, BAG3 cooperates with the molecular chaperones Hsc70 and HspB8 to induce the degradation of mechanically damaged cytoskeleton components in lysosomes. This process is called [[chaperone-assisted selective autophagy]] and is essential for maintaining muscle activity in flies, mice and men.<ref name="pmid20060297" />


BAG3 is able to stimulate the expression of [[cytoskeleton]] proteins in response to mechanical tension by activating the [[transcription (genetics)|transcription]] regulators [[YAP1]] and [[WWTR1]].<ref name="pmid23434281" /> BAG3 balances protein synthesis and protein degradation under mechanical stress.
BAG3 is able to stimulate the expression of [[cytoskeleton]] proteins in response to mechanical tension by activating the [[transcription (genetics)|transcription]] regulators [[YAP1]] and [[WWTR1]].<ref name="pmid23434281" /> BAG3 balances protein synthesis and protein degradation under mechanical stress.


== Interactions ==
== Interactions ==

BAG3 has been shown to [[Protein-protein interaction|interact]] with:
PLCG1 has been shown to [[Protein-protein interaction|interact]] with:
* [[AMOTL1]]<ref name = "pmid23434281" />
{{div col|colwidth=20em}}
* [[Dynein]],<ref>[http://www.nature.com/embor/journal/v12/n2/full/embor2010203a.html Gamerdinger et al., 2011 BAG3 mediates chaperone-based aggresome-targeting and selective autophagy of misfolded proteins.]</ref>
* [[HSPA1A]],<ref name = pmid10980614>{{cite journal | date = September 2000 | author = Doong H, Price J, Kim YS, Gasbarre C, Probst J, Liotta LA, Blanchette J, Rizzo K, Kohn E | title = CAIR-1/BAG-3 forms an EGF-regulated ternary complex with phospholipase C-gamma and Hsp70/Hsc70 | journal = Oncogene | volume = 19 | issue = 38 | pages = 4385-95 | pmid = 10980614 | doi = 10.1038/sj.onc.1203797}}</ref><ref name = pmid11527400>{{cite journal | date = September 2001 | author = Antoku K, Maser RS, Scully WJ, Delach SM, Johnson DE | title = Isolation of Bcl-2 binding proteins that exhibit homology with BAG-1 and suppressor of death domains protein | journal = Biochem. Biophys. Res. Commun. | volume = 286 | issue = 5 | pages = 1003-10 | pmid = 11527400 | doi = 10.1006/bbrc.2001.5512}}</ref>
* [[FGFR1]],<ref name = pmid10980614>{{cite journal | vauthors = Doong H, Price J, Kim YS, Gasbarre C, Probst J, Liotta LA, Blanchette J, Rizzo K, Kohn E | title = CAIR-1/BAG-3 forms an EGF-regulated ternary complex with phospholipase C-gamma and Hsp70/Hsc70 | journal = Oncogene | volume = 19 | issue = 38 | pages = 4385–95 | pmid = 10980614 | doi = 10.1038/sj.onc.1203797 | date=September 2000| doi-access = free }}</ref>
* [[CD117]],<ref name = pmid11071635>{{cite journal | vauthors = van Dijk TB, van Den Akker E, Amelsvoort MP, Mano H, Löwenberg B, von Lindern M | title = Stem cell factor induces phosphatidylinositol 3'-kinase-dependent Lyn/Tec/Dok-1 complex formation in hematopoietic cells | journal = Blood | volume = 96 | issue = 10 | pages = 3406–13 | pmid = 11071635 | doi = 10.1182/blood.V96.10.3406| date=November 2000| url = https://pure.eur.nl/en/publications/395fb5fc-60e3-45d7-a9b1-fc7b9cc6b4bc | hdl = 1765/9530 | hdl-access = free }}</ref><ref name = pmid7536744>{{cite journal | vauthors = Jhun BH, Rivnay B, Price D, Avraham H | title = The MATK tyrosine kinase interacts in a specific and SH2-dependent manner with c-Kit | journal = J. Biol. Chem. | volume = 270 | issue = 16 | pages = 9661–6 | pmid = 7536744 | doi = 10.1074/jbc.270.16.9661 | date=April 1995| doi-access = free }}</ref>
* [[HSPA8]],<ref name = pmid9873016>{{cite journal | date = January 1999 | author = Takayama S, Xie Z, Reed JC | title = An evolutionarily conserved family of Hsp70/Hsc70 molecular chaperone regulators | journal = J. Biol. Chem. | volume = 274 | issue = 2 | pages = 781-6 | pmid = 9873016 | doi = }}</ref>
* [[CD31]],<ref name = pmid10350061>{{cite journal | vauthors = Pumphrey NJ, Taylor V, Freeman S, Douglas MR, Bradfield PF, Young SP, Lord JM, Wakelam MJ, Bird IN, Salmon M, Buckley CD | title = Differential association of cytoplasmic signalling molecules SHP-1, SHP-2, SHIP and phospholipase C-gamma1 with PECAM-1/CD31 | journal = FEBS Lett. | volume = 450 | issue = 1–2 | pages = 77–83 | pmid = 10350061 | doi = 10.1016/s0014-5793(99)00446-9 | date=April 1999| s2cid = 31471121 | doi-access = free }}</ref>
* [[LATS1]],
* [[Cbl gene]]<ref name = pmid12061819/><ref name = pmid9712732>{{cite journal | vauthors = Graham LJ, Stoica BA, Shapiro M, DeBell KE, Rellahan B, Laborda J, Bonvini E | title = Sequences surrounding the Src-homology 3 domain of phospholipase Cgamma-1 increase the domain's association with Cbl | journal = Biochem. Biophys. Res. Commun. | volume = 249 | issue = 2 | pages = 537–41 | pmid = 9712732 | doi = 10.1006/bbrc.1998.9177 | date=August 1998}}</ref>
* [[PLCG1]],<ref name = pmid10980614/> and
*[[CISH (gene)|CISH]]<ref>{{cite journal|last1=Palmer|first1=Douglas|title=Cish actively silences TCR signaling in CD8+ T cells to maintain tumor tolerance.|journal=J Exp Med|date=Nov 2, 2015|pmid=26527801|doi=10.1084/jem.20150304|volume=212|issue=12|pages=2095–113|pmc=4647263}}</ref>
* [[SYNPO2]].
* [[Epidermal growth factor receptor]],<ref name = pmid12061819>{{cite journal | vauthors = Tvorogov D, Carpenter G | title = EGF-dependent association of phospholipase C-gamma1 with c-Cbl | journal = Exp. Cell Res. | volume = 277 | issue = 1 | pages = 86–94 | pmid = 12061819 | doi = 10.1006/excr.2002.5545 | date=July 2002}}</ref><ref name = pmid9207933>{{cite journal | vauthors = Bedrin MS, Abolafia CM, Thompson JF | title = Cytoskeletal association of epidermal growth factor receptor and associated signaling proteins is regulated by cell density in IEC-6 intestinal cells | journal = J. Cell. Physiol. | volume = 172 | issue = 1 | pages = 126–36 | pmid = 9207933 | doi = 10.1002/(SICI)1097-4652(199707)172:1<126::AID-JCP14>3.0.CO;2-A | date=July 1997| s2cid = 24571987 }}</ref>
{{-}}
* [[Eukaryotic translation elongation factor 1 alpha 1]],<ref name = pmid11886851>{{cite journal | vauthors = Chang JS, Seok H, Kwon TK, Min DS, Ahn BH, Lee YH, Suh JW, Kim JW, Iwashita S, Omori A, Ichinose S, Numata O, Seo JK, Oh YS, Suh PG | title = Interaction of elongation factor-1alpha and pleckstrin homology domain of phospholipase C-gamma 1 with activating its activity | journal = J. Biol. Chem. | volume = 277 | issue = 22 | pages = 19697–702 | pmid = 11886851 | doi = 10.1074/jbc.M111206200 | date=May 2002| s2cid = 86109770 | url = http://kumel.medlib.dsmc.or.kr/bitstream/2015.oak/33741/1/oak-aaa-2340.pdf | doi-access = free }}</ref>
* [[FLT1]],<ref name = pmid9398617>{{cite journal | vauthors = Cunningham SA, Arrate MP, Brock TA, Waxham MN | title = Interactions of FLT-1 and KDR with phospholipase C gamma: identification of the phosphotyrosine binding sites | journal = Biochem. Biophys. Res. Commun. | volume = 240 | issue = 3 | pages = 635–9 | pmid = 9398617 | doi = 10.1006/bbrc.1997.7719 | date=November 1997}}</ref>
* [[GAB1]],<ref name = pmid11507676>{{cite journal | vauthors = Ueno E, Haruta T, Uno T, Usui I, Iwata M, Takano A, Kawahara J, Sasaoka T, Ishibashi O, Kobayashi M | title = Potential role of Gab1 and phospholipase C-gamma in osmotic shock-induced glucose uptake in 3T3-L1 adipocytes | journal = Horm. Metab. Res. | volume = 33 | issue = 7 | pages = 402–6 | pmid = 11507676 | doi = 10.1055/s-2001-16227 | date=July 2001| s2cid = 9125865 }}</ref><ref name = pmid8596638>{{cite journal | vauthors = Holgado-Madruga M, Emlet DR, Moscatello DK, Godwin AK, Wong AJ | title = A Grb2-associated docking protein in EGF- and insulin-receptor signalling | journal = Nature | volume = 379 | issue = 6565 | pages = 560–4 | pmid = 8596638 | doi = 10.1038/379560a0 | date=February 1996| bibcode = 1996Natur.379..560H | s2cid = 4271970 }}</ref>
* [[GIT1]],<ref name = pmid14523024>{{cite journal | vauthors = Haendeler J, Yin G, Hojo Y, Saito Y, Melaragno M, Yan C, Sharma VK, Heller M, Aebersold R, Berk BC | title = GIT1 mediates Src-dependent activation of phospholipase Cgamma by angiotensin II and epidermal growth factor | journal = J. Biol. Chem. | volume = 278 | issue = 50 | pages = 49936–44 | pmid = 14523024 | doi = 10.1074/jbc.M307317200 | date=December 2003| doi-access = free }}</ref>
* [[Grb2]],<ref name = pmid9281317>{{cite journal | vauthors = Pei Z, Maloney JA, Yang L, Williamson JR | title = A new function for phospholipase C-gamma1: coupling to the adaptor protein GRB2 | journal = Arch. Biochem. Biophys. | volume = 345 | issue = 1 | pages = 103–10 | pmid = 9281317 | doi = 10.1006/abbi.1997.0245 | date=September 1997| doi-access = free }}</ref><ref name = pmid7629168>{{cite journal | vauthors = Nel AE, Gupta S, Lee L, Ledbetter JA, Kanner SB | title = Ligation of the T-cell antigen receptor (TCR) induces association of hSos1, ZAP-70, phospholipase C-gamma 1, and other phosphoproteins with Grb2 and the zeta-chain of the TCR | journal = J. Biol. Chem. | volume = 270 | issue = 31 | pages = 18428–36 | pmid = 7629168 | doi = 10.1074/jbc.270.31.18428 | date=August 1995| doi-access = free }}</ref><ref name = pmid10940929>{{cite journal | vauthors = Scholler JK, Perez-Villar JJ, O'Day K, Kanner SB | title = Engagement of the T lymphocyte antigen receptor regulates association of son-of-sevenless homologues with the SH3 domain of phospholipase Cgamma1 | journal = Eur. J. Immunol. | volume = 30 | issue = 8 | pages = 2378–87 | pmid = 10940929 | doi = 10.1002/1521-4141(2000)30:8<2378::AID-IMMU2378>3.0.CO;2-E | date=August 2000| doi-access = free }}</ref>
* [[HER2/neu]],<ref name = pmid1676673>{{cite journal | vauthors = Peles E, Levy RB, Or E, Ullrich A, Yarden Y | title = Oncogenic forms of the neu/HER2 tyrosine kinase are permanently coupled to phospholipase C gamma | journal = EMBO J. | volume = 10 | issue = 8 | pages = 2077–86 | pmid = 1676673 | pmc = 452891 | doi = 10.1002/j.1460-2075.1991.tb07739.x| date=August 1991}}</ref><ref name = pmid1683701>{{cite journal | vauthors = Arteaga CL, Johnson MD, Todderud G, Coffey RJ, Carpenter G, Page DL | title = Elevated content of the tyrosine kinase substrate phospholipase C-gamma 1 in primary human breast carcinomas | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 88 | issue = 23 | pages = 10435–9 | pmid = 1683701 | pmc = 52943 | doi = 10.1073/pnas.88.23.10435| year = 1991 | bibcode = 1991PNAS...8810435A | doi-access = free }}</ref>
* [[IRS2]],<ref name = pmid9535722>{{cite journal | vauthors = Sozzani P, Hasan L, Séguélas MH, Caput D, Ferrara P, Pipy B, Cambon C | title = IL-13 induces tyrosine phosphorylation of phospholipase C gamma-1 following IRS-2 association in human monocytes: relationship with the inhibitory effect of IL-13 on ROI production | journal = Biochem. Biophys. Res. Commun. | volume = 244 | issue = 3 | pages = 665–70 | pmid = 9535722 | doi = 10.1006/bbrc.1998.8314 | date=March 1998}}</ref>
* [[ITK (gene)|ITK]],<ref name = pmid10586033>{{cite journal | vauthors = Perez-Villar JJ, Kanner SB | title = Regulated association between the tyrosine kinase Emt/Itk/Tsk and phospholipase-C gamma 1 in human T lymphocytes | journal = J. Immunol. | volume = 163 | issue = 12 | pages = 6435–41 | pmid = 10586033 | date=December 1999| doi = 10.4049/jimmunol.163.12.6435 | s2cid = 20465805 | doi-access = free }}</ref><ref name = pmid12163161>{{cite journal | vauthors = Hao S, August A | title = The proline rich region of the Tec homology domain of ITK regulates its activity | journal = FEBS Lett. | volume = 525 | issue = 1–3 | pages = 53–8 | pmid = 12163161 | doi = 10.1016/s0014-5793(02)03066-1 | date=August 2002| s2cid = 21541455 | doi-access = free }}</ref>
* [[KHDRBS1]],<ref name = pmid11960376>{{cite journal | vauthors = Oneyama C, Nakano H, Sharma SV | title = UCS15A, a novel small molecule, SH3 domain-mediated protein-protein interaction blocking drug | journal = Oncogene | volume = 21 | issue = 13 | pages = 2037–50 | pmid = 11960376 | doi = 10.1038/sj.onc.1205271 | date=March 2002| doi-access = free }}</ref><ref name = pmid9743338>{{cite journal | vauthors = Jabado N, Jauliac S, Pallier A, Bernard F, Fischer A, Hivroz C | title = Sam68 association with p120GAP in CD4+ T cells is dependent on CD4 molecule expression | journal = J. Immunol. | volume = 161 | issue = 6 | pages = 2798–803 | pmid = 9743338 | date=September 1998| doi = 10.4049/jimmunol.161.6.2798 | s2cid = 10463909 | doi-access = free }}</ref><ref name = pmid10467411>{{cite journal | vauthors = Shen Z, Batzer A, Koehler JA, Polakis P, Schlessinger J, Lydon NB, Moran MF | title = Evidence for SH3 domain directed binding and phosphorylation of Sam68 by Src | journal = Oncogene | volume = 18 | issue = 33 | pages = 4647–53 | pmid = 10467411 | doi = 10.1038/sj.onc.1203079 | date=August 1999| doi-access = free }}</ref>
* [[Linker of activated T cells]],<ref name = pmid9729044>{{cite journal | vauthors = Zhang W, Trible RP, Samelson LE | title = LAT palmitoylation: its essential role in membrane microdomain targeting and tyrosine phosphorylation during T cell activation | journal = Immunity | volume = 9 | issue = 2 | pages = 239–46 | pmid = 9729044 | doi = 10.1016/s1074-7613(00)80606-8 | date=August 1998| doi-access = free }}</ref><ref name = pmid11368773>{{cite journal | vauthors = Paz PE, Wang S, Clarke H, Lu X, Stokoe D, Abo A | title = Mapping the Zap-70 phosphorylation sites on LAT (linker for activation of T cells) required for recruitment and activation of signalling proteins in T cells | journal = Biochem. J. | volume = 356 | issue = Pt 2 | pages = 461–71 | pmid = 11368773 | pmc = 1221857 | doi = 10.1042/0264-6021:3560461| year = 2001 }}</ref><ref name = pmid9489702>{{cite journal | vauthors = Zhang W, Sloan-Lancaster J, Kitchen J, Trible RP, Samelson LE | title = LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation | journal = Cell | volume = 92 | issue = 1 | pages = 83–92 | pmid = 9489702 | doi = 10.1016/S0092-8674(00)80901-0 | date=January 1998| s2cid = 1806525 | doi-access = free }}</ref>
* [[Lymphocyte cytosolic protein 2]],<ref name = pmid11390650>{{cite journal | vauthors = Yablonski D, Kadlecek T, Weiss A | title = Identification of a phospholipase C-gamma1 (PLC-gamma1) SH3 domain-binding site in SLP-76 required for T-cell receptor-mediated activation of PLC-gamma1 and NFAT | journal = Mol. Cell. Biol. | volume = 21 | issue = 13 | pages = 4208–18 | pmid = 11390650 | pmc = 87082 | doi = 10.1128/MCB.21.13.4208-4218.2001 | year = 2001 }}</ref>
* [[PDGFRA]],<ref name = pmid7535778>{{cite journal | vauthors = Eriksson A, Nånberg E, Rönnstrand L, Engström U, Hellman U, Rupp E, Carpenter G, Heldin CH, Claesson-Welsh L | title = Demonstration of functionally different interactions between phospholipase C-gamma and the two types of platelet-derived growth factor receptors | journal = J. Biol. Chem. | volume = 270 | issue = 13 | pages = 7773–81 | pmid = 7535778 | doi = 10.1074/jbc.270.13.7773 | date=March 1995| doi-access = free }}</ref>
* [[PLD2]],<ref name = pmid12646582>{{cite journal | vauthors = Jang IH, Lee S, Park JB, Kim JH, Lee CS, Hur EM, Kim IS, Kim KT, Yagisawa H, Suh PG, Ryu SH | title = The direct interaction of phospholipase C-gamma 1 with phospholipase D2 is important for epidermal growth factor signaling | journal = J. Biol. Chem. | volume = 278 | issue = 20 | pages = 18184–90 | pmid = 12646582 | doi = 10.1074/jbc.M208438200 | date=May 2003| doi-access = free }}</ref>
* [[RHOA]],<ref name = pmid12071848>{{cite journal | vauthors = Thodeti CK, Massoumi R, Bindslev L, Sjölander A | title = Leukotriene D4 induces association of active RhoA with phospholipase C-gamma1 in intestinal epithelial cells | journal = Biochem. J. | volume = 365 | issue = Pt 1 | pages = 157–63 | pmid = 12071848 | pmc = 1222665 | doi = 10.1042/BJ20020248 | year = 2002 }}</ref>
* [[SOS1]],<ref name = pmid10940929/><ref name = pmid10913276>{{cite journal | vauthors = Kim MJ, Chang JS, Park SK, Hwang JI, Ryu SH, Suh PG | title = Direct interaction of SOS1 Ras exchange protein with the SH3 domain of phospholipase C-gamma1 | journal = Biochemistry | volume = 39 | issue = 29 | pages = 8674–82 | pmid = 10913276 | doi = 10.1021/bi992558t | date=July 2000}}</ref>
* [[TUB (gene)|TUB]],<ref name = pmid10455176>{{cite journal | vauthors = Kapeller R, Moriarty A, Strauss A, Stubdal H, Theriault K, Siebert E, Chickering T, Morgenstern JP, Tartaglia LA, Lillie J | title = Tyrosine phosphorylation of tub and its association with Src homology 2 domain-containing proteins implicate tub in intracellular signaling by insulin | journal = J. Biol. Chem. | volume = 274 | issue = 35 | pages = 24980–6 | pmid = 10455176 | doi = 10.1074/jbc.274.35.24980 | date=August 1999| doi-access = free }}</ref>
* [[TrkA]],<ref name = pmid1715690>{{cite journal | vauthors = Ohmichi M, Decker SJ, Pang L, Saltiel AR | title = Nerve growth factor binds to the 140 kd trk proto-oncogene product and stimulates its association with the src homology domain of phospholipase C gamma 1 | journal = Biochem. Biophys. Res. Commun. | volume = 179 | issue = 1 | pages = 217–23 | pmid = 1715690 | doi = 10.1016/0006-291x(91)91357-i | date=August 1991| hdl = 2027.42/29169 | hdl-access = free }}</ref><ref name = pmid9856458>{{cite journal | vauthors = Qian X, Riccio A, Zhang Y, Ginty DD | title = Identification and characterization of novel substrates of Trk receptors in developing neurons | journal = Neuron | volume = 21 | issue = 5 | pages = 1017–29 | pmid = 9856458 | doi = 10.1016/s0896-6273(00)80620-0 | date=November 1998| s2cid = 12354383 | doi-access = free }}</ref><ref name = pmid10092678>{{cite journal | vauthors = Meakin SO, MacDonald JI, Gryz EA, Kubu CJ, Verdi JM | title = The signaling adapter FRS-2 competes with Shc for binding to the nerve growth factor receptor TrkA. A model for discriminating proliferation and differentiation | journal = J. Biol. Chem. | volume = 274 | issue = 14 | pages = 9861–70 | pmid = 10092678 | doi = 10.1074/jbc.274.14.9861 | date=April 1999| doi-access = free }}</ref><ref name = pmid10708759>{{cite journal | vauthors = Koch A, Mancini A, Stefan M, Niedenthal R, Niemann H, Tamura T | title = Direct interaction of nerve growth factor receptor, TrkA, with non-receptor tyrosine kinase, c-Abl, through the activation loop | journal = FEBS Lett. | volume = 469 | issue = 1 | pages = 72–6 | pmid = 10708759 | doi = 10.1016/s0014-5793(00)01242-4 | date=March 2000| s2cid = 28312468 | doi-access = free }}</ref>
* [[TrkB]],<ref name = pmid10092678/><ref name = pmid12074588>{{cite journal | vauthors = Suzuki S, Mizutani M, Suzuki K, Yamada M, Kojima M, Hatanaka H, Koizumi S | title = Brain-derived neurotrophic factor promotes interaction of the Nck2 adaptor protein with the TrkB tyrosine kinase receptor | journal = Biochem. Biophys. Res. Commun. | volume = 294 | issue = 5 | pages = 1087–92 | pmid = 12074588 | doi = 10.1016/S0006-291X(02)00606-X | date=June 2002}}</ref>
* [[VAV1]],<ref name = pmid9891995>{{cite journal | vauthors = Bertagnolo V, Marchisio M, Volinia S, Caramelli E, Capitani S | title = Nuclear association of tyrosine-phosphorylated Vav to phospholipase C-gamma1 and phosphoinositide 3-kinase during granulocytic differentiation of HL-60 cells | journal = FEBS Lett. | volume = 441 | issue = 3 | pages = 480–4 | pmid = 9891995 | doi = 10.1016/s0014-5793(98)01593-2 | date=December 1998| s2cid = 38371954 | doi-access = free }}</ref> and
* [[Wiskott-Aldrich syndrome protein]].<ref name = pmid8805332>{{cite journal | vauthors = Banin S, Truong O, Katz DR, Waterfield MD, Brickell PM, Gout I | title = Wiskott-Aldrich syndrome protein (WASp) is a binding partner for c-Src family protein-tyrosine kinases | journal = Curr. Biol. | volume = 6 | issue = 8 | pages = 981–8 | pmid = 8805332 | doi = 10.1016/s0960-9822(02)00642-5 | date=August 1996| s2cid = 162267 | doi-access = free }}</ref><ref name = pmid8824280>{{cite journal | vauthors = Finan PM, Soames CJ, Wilson L, Nelson DL, Stewart DM, Truong O, Hsuan JJ, Kellie S | title = Identification of regions of the Wiskott-Aldrich syndrome protein responsible for association with selected Src homology 3 domains | journal = J. Biol. Chem. | volume = 271 | issue = 42 | pages = 26291–5 | pmid = 8824280 | doi = 10.1074/jbc.271.42.26291 | date=October 1996| doi-access = free }}</ref>
{{Div col end}}

== References ==
== References ==
{{Reflist|35em}}
{{Reflist|35em}}


==Further reading==
== Further reading ==
{{Refbegin|35em}}
{{Refbegin|35em}}
*{{cite journal | author=Maruyama K, Sugano S |title=Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. |journal=Gene |volume=138 |issue= 1-2 |pages= 171–4 |year= 1994 |pmid= 8125298 |doi=10.1016/0378-1119(94)90802-8 }}
* {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1–2 | pages = 171–4 | date = Jan 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }}
*{{cite journal | author=Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. |title=Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. |journal=Gene |volume=200 |issue= 1-2 |pages= 149–56 |year= 1997 |pmid= 9373149 |doi=10.1016/S0378-1119(97)00411-3 }}
* {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1–2 | pages = 149–56 | date = Oct 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }}
*{{cite journal | author=Lee JH, Takahashi T, Yasuhara N, et al. |title=Bis, a Bcl-2-binding protein that synergizes with Bcl-2 in preventing cell death. |journal=Oncogene |volume=18 |issue= 46 |pages= 6183–90 |year= 2000 |pmid= 10597216 |doi= 10.1038/sj.onc.1203043 }}
* {{cite journal | vauthors = Lee JH, Takahashi T, Yasuhara N, Inazawa J, Kamada S, Tsujimoto Y | title = Bis, a Bcl-2-binding protein that synergizes with Bcl-2 in preventing cell death | journal = Oncogene | volume = 18 | issue = 46 | pages = 6183–90 | date = Nov 1999 | pmid = 10597216 | doi = 10.1038/sj.onc.1203043 | doi-access = free }}
*{{cite journal | author=Doong H, Price J, Kim YS, et al. |title=CAIR-1/BAG-3 forms an EGF-regulated ternary complex with phospholipase C-gamma and Hsp70/Hsc70. |journal=Oncogene |volume=19 |issue= 38 |pages= 4385–95 |year= 2000 |pmid= 10980614 |doi= 10.1038/sj.onc.1203797 }}
* {{cite journal | vauthors = Doong H, Price J, Kim YS, Gasbarre C, Probst J, Liotta LA, Blanchette J, Rizzo K, Kohn E | title = CAIR-1/BAG-3 forms an EGF-regulated ternary complex with phospholipase C-gamma and Hsp70/Hsc70 | journal = Oncogene | volume = 19 | issue = 38 | pages = 4385–95 | date = Sep 2000 | pmid = 10980614 | doi = 10.1038/sj.onc.1203797 | doi-access = free }}
*{{cite journal | author=Liao Q, Ozawa F, Friess H, et al. |title=The anti-apoptotic protein BAG-3 is overexpressed in pancreatic cancer and induced by heat stress in pancreatic cancer cell lines. |journal=FEBS Lett. |volume=503 |issue= 2-3 |pages= 151–7 |year= 2001 |pmid= 11513873 |doi=10.1016/S0014-5793(01)02728-4 }}
* {{cite journal | vauthors = Liao Q, Ozawa F, Friess H, Zimmermann A, Takayama S, Reed JC, Kleeff J, Büchler MW | title = The anti-apoptotic protein BAG-3 is overexpressed in pancreatic cancer and induced by heat stress in pancreatic cancer cell lines | journal = FEBS Letters | volume = 503 | issue = 2–3 | pages = 151–7 | date = Aug 2001 | pmid = 11513873 | doi = 10.1016/S0014-5793(01)02728-4 | s2cid = 10672504 | doi-access = free }}
*{{cite journal | author=Antoku K, Maser RS, Scully WJ, et al. |title=Isolation of Bcl-2 binding proteins that exhibit homology with BAG-1 and suppressor of death domains protein. |journal=Biochem. Biophys. Res. Commun. |volume=286 |issue= 5 |pages= 1003–10 |year= 2001 |pmid= 11527400 |doi= 10.1006/bbrc.2001.5512 }}
* {{cite journal | vauthors = Antoku K, Maser RS, Scully WJ, Delach SM, Johnson DE | title = Isolation of Bcl-2 binding proteins that exhibit homology with BAG-1 and suppressor of death domains protein | journal = Biochemical and Biophysical Research Communications | volume = 286 | issue = 5 | pages = 1003–10 | date = Sep 2001 | pmid = 11527400 | doi = 10.1006/bbrc.2001.5512 }}
*{{cite journal | author=Suzuki H, Fukunishi Y, Kagawa I, et al. |title=Protein-protein interaction panel using mouse full-length cDNAs. |journal=Genome Res. |volume=11 |issue= 10 |pages= 1758–65 |year= 2001 |pmid= 11591653 |doi= 10.1101/gr.180101 | pmc=311163 }}
* {{cite journal | vauthors = Suzuki H, Fukunishi Y, Kagawa I, Saito R, Oda H, Endo T, Kondo S, Bono H, Okazaki Y, Hayashizaki Y | title = Protein-protein interaction panel using mouse full-length cDNAs | journal = Genome Research | volume = 11 | issue = 10 | pages = 1758–65 | date = Oct 2001 | pmid = 11591653 | pmc = 311163 | doi = 10.1101/gr.180101 }}
*{{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 | pmc=139241 }}
* {{cite journal | vauthors = Romano MF, Festa M, Pagliuca G, Lerose R, Bisogni R, Chiurazzi F, Storti G, Volpe S, Venuta S, Turco MC, Leone A | title = BAG3 protein controls B-chronic lymphocytic leukaemia cell apoptosis | journal = Cell Death and Differentiation | volume = 10 | issue = 3 | pages = 383–5 | date = Mar 2003 | pmid = 12700638 | doi = 10.1038/sj.cdd.4401167 | doi-access = free }}
*{{cite journal | author=Romano MF, Festa M, Pagliuca G, et al. |title=BAG3 protein controls B-chronic lymphocytic leukaemia cell apoptosis. |journal=Cell Death Differ. |volume=10 |issue= 3 |pages= 383–5 |year= 2003 |pmid= 12700638 |doi= 10.1038/sj.cdd.4401167 }}
* {{cite journal | vauthors = Pagliuca MG, Lerose R, Cigliano S, Leone A | title = Regulation by heavy metals and temperature of the human BAG-3 gene, a modulator of Hsp70 activity | journal = FEBS Letters | volume = 541 | issue = 1–3 | pages = 11–5 | date = Apr 2003 | pmid = 12706811 | doi = 10.1016/S0014-5793(03)00274-6 | s2cid = 33081500 | doi-access = free }}
*{{cite journal | author=Pagliuca MG, Lerose R, Cigliano S, Leone A |title=Regulation by heavy metals and temperature of the human BAG-3 gene, a modulator of Hsp70 activity. |journal=FEBS Lett. |volume=541 |issue= 1-3 |pages= 11–5 |year= 2003 |pmid= 12706811 |doi=10.1016/S0014-5793(03)00274-6 }}
* {{cite journal | vauthors = Doong H, Rizzo K, Fang S, Kulpa V, Weissman AM, Kohn EC | title = CAIR-1/BAG-3 abrogates heat shock protein-70 chaperone complex-mediated protein degradation: accumulation of poly-ubiquitinated Hsp90 client proteins | journal = The Journal of Biological Chemistry | volume = 278 | issue = 31 | pages = 28490–500 | date = Aug 2003 | pmid = 12750378 | doi = 10.1074/jbc.M209682200 | doi-access = free }}
*{{cite journal | author=Doong H, Rizzo K, Fang S, et al. |title=CAIR-1/BAG-3 abrogates heat shock protein-70 chaperone complex-mediated protein degradation: accumulation of poly-ubiquitinated Hsp90 client proteins. |journal=J. Biol. Chem. |volume=278 |issue= 31 |pages= 28490–500 |year= 2003 |pmid= 12750378 |doi= 10.1074/jbc.M209682200 }}
* {{cite journal | vauthors = Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP | title = Large-scale characterization of HeLa cell nuclear phosphoproteins | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 33 | pages = 12130–5 | date = Aug 2004 | pmid = 15302935 | pmc = 514446 | doi = 10.1073/pnas.0404720101 | bibcode = 2004PNAS..10112130B | doi-access = free }}
*{{cite journal | author=Beausoleil SA, Jedrychowski M, Schwartz D, et al. |title=Large-scale characterization of HeLa cell nuclear phosphoproteins. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=101 |issue= 33 |pages= 12130–5 |year= 2004 |pmid= 15302935 |doi= 10.1073/pnas.0404720101 | pmc=514446 }}
* {{cite journal | vauthors = Rush J, Moritz A, Lee KA, Guo A, Goss VL, Spek EJ, Zhang H, Zha XM, Polakiewicz RD, Comb MJ | title = Immunoaffinity profiling of tyrosine phosphorylation in cancer cells | journal = Nature Biotechnology | volume = 23 | issue = 1 | pages = 94–101 | date = Jan 2005 | pmid = 15592455 | doi = 10.1038/nbt1046 | s2cid = 7200157 }}
*{{cite journal | author=Gerhard DS, Wagner L, Feingold EA, et al. |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 | pmc=528928 }}
* {{cite journal | vauthors = Tao WA, Wollscheid B, O'Brien R, Eng JK, Li XJ, Bodenmiller B, Watts JD, Hood L, Aebersold R | title = Quantitative phosphoproteome analysis using a dendrimer conjugation chemistry and tandem mass spectrometry | journal = Nature Methods | volume = 2 | issue = 8 | pages = 591–8 | date = Aug 2005 | pmid = 16094384 | doi = 10.1038/nmeth776 | s2cid = 20475874 }}
*{{cite journal | author=Rush J, Moritz A, Lee KA, et al. |title=Immunoaffinity profiling of tyrosine phosphorylation in cancer cells. |journal=Nat. Biotechnol. |volume=23 |issue= 1 |pages= 94–101 |year= 2005 |pmid= 15592455 |doi= 10.1038/nbt1046 }}
* {{cite journal | vauthors = Seo YJ, Jeon MH, Lee JH, Lee YJ, Youn HJ, Ko JH, Lee JH | title = Bis induces growth inhibition and differentiation of HL-60 cells via up-regulation of p27 | journal = Experimental & Molecular Medicine | volume = 37 | issue = 6 | pages = 624–30 | date = Dec 2005 | pmid = 16391524 | doi = 10.1038/emm.2005.76 | doi-access = free }}
*{{cite journal | author=Tao WA, Wollscheid B, O'Brien R, et al. |title=Quantitative phosphoproteome analysis using a dendrimer conjugation chemistry and tandem mass spectrometry. |journal=Nat. Methods |volume=2 |issue= 8 |pages= 591–8 |year= 2005 |pmid= 16094384 |doi= 10.1038/nmeth776 }}
* {{cite journal | vauthors = Kassis JN, Guancial EA, Doong H, Virador V, Kohn EC | title = CAIR-1/BAG-3 modulates cell adhesion and migration by downregulating activity of focal adhesion proteins | journal = Experimental Cell Research | volume = 312 | issue = 15 | pages = 2962–71 | date = Sep 2006 | pmid = 16859681 | doi = 10.1016/j.yexcr.2006.05.023 | url = https://zenodo.org/record/1259459 }}
*{{cite journal | author=Rual JF, Venkatesan K, Hao T, et al. |title=Towards a proteome-scale map of the human protein-protein interaction network. |journal=Nature |volume=437 |issue= 7062 |pages= 1173–8 |year= 2005 |pmid= 16189514 |doi= 10.1038/nature04209 }}
* {{cite journal | vauthors = Beausoleil SA, Villén J, Gerber SA, Rush J, Gygi SP | title = A probability-based approach for high-throughput protein phosphorylation analysis and site localization | journal = Nature Biotechnology | volume = 24 | issue = 10 | pages = 1285–92 | date = Oct 2006 | pmid = 16964243 | doi = 10.1038/nbt1240 | s2cid = 14294292 }}
*{{cite journal | author=Seo YJ, Jeon MH, Lee JH, et al. |title=Bis induces growth inhibition and differentiation of HL-60 cells via up-regulation of p27. |journal=Exp. Mol. Med. |volume=37 |issue= 6 |pages= 624–30 |year= 2006 |pmid= 16391524 |doi= }}
*{{cite journal | author=Kassis JN, Guancial EA, Doong H, et al. |title=CAIR-1/BAG-3 modulates cell adhesion and migration by downregulating activity of focal adhesion proteins. |journal=Exp. Cell Res. |volume=312 |issue= 15 |pages= 2962–71 |year= 2006 |pmid= 16859681 |doi= 10.1016/j.yexcr.2006.05.023 }}
*{{cite journal | author=Beausoleil SA, Villén J, Gerber SA, et al. |title=A probability-based approach for high-throughput protein phosphorylation analysis and site localization. |journal=Nat. Biotechnol. |volume=24 |issue= 10 |pages= 1285–92 |year= 2006 |pmid= 16964243 |doi= 10.1038/nbt1240 }}
{{Refend}}
{{Refend}}


== External links ==
== External links ==
* [http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=mfm GeneReviews/NIH/NCBI/UW entry on Myofibrillar Myopathy]
* [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=mfm GeneReviews/NIH/NCBI/UW entry on Myofibrillar Myopathy]
* {{UCSC gene info|BAG3}}
* {{PDBe-KB2|Q9JLV1|Mouse BAG family molecular chaperone regulator 3}}


{{PDB Gallery|geneid=9531}}
{{PDB Gallery|geneid=9531}}
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{{DEFAULTSORT:Bag3}}
{{DEFAULTSORT:Bag3}}
[[Category:Ageing]]
[[Category:Ageing]]
⚫
[[Category:Genetics]]
[[Category:Aging-related genes]]
[[Category:Aging-related genes]]
[[Category:Aging-related proteins]]
[[Category:Aging-related proteins]]
⚫
[[Category:Co-chaperones]]


{{Gene-10-stub}}

Latest revision as of 04:28, 6 January 2024

BAG3
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesBAG3, BAG-3, BIS, CAIR-1, MFM6, BCL2 associated athanogene 3, BAG cochaperone 3
External IDsOMIM: 603883; MGI: 1352493; HomoloGene: 3162; GeneCards: BAG3; OMA:BAG3 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

9531

29810

Ensembl

ENSG00000151929

ENSMUSG00000030847

UniProt

O95817

Q9JLV1

RefSeq (mRNA)

NM_004281

NM_013863

RefSeq (protein)

NP_004272

NP_038891

Location (UCSC)Chr 10: 119.65 – 119.68 MbChr 7: 128.13 – 128.15 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

BAG family molecular chaperone regulator 3 is a protein that in humans is encoded by the BAG3 gene. BAG3 is involved in chaperone-assisted selective autophagy.[5][6][7][8][9]

Function

[edit]

BAG proteins compete with Hip-1 for binding to the Hsc70/Hsp70 ATPase domain and promote substrate release. All the BAG proteins have an approximately 45-amino acid BAG domain near the C terminus but differ markedly in their N-terminal regions. The protein encoded by this gene contains a WW domain in the N-terminal region and a BAG domain in the C-terminal region. The BAG domains of BAG1, BAG2, and BAG3 interact specifically with the Hsc70 ATPase domain in vitro and in mammalian cells. All 3 proteins bind with high affinity to the ATPase domain of Hsc70 and inhibit its chaperone activity in a Hip-repressible manner.[7]

Clinical significance

[edit]

BAG gene has been implicated in age related neurodegenerative diseases such as Alzheimer's. It has been demonstrated that BAG1 and BAG3 regulate the proteasomal and lysosomal protein elimination pathways, respectively.[10][11] It has also been shown to be a cause of familial dilated cardiomyopathy.[12] That BAG3 mutations are responsible for familial dilated cardiomyopathy is confirmed by another study describing 6 new molecular variants (2 missense and 4 premature Stops ). Moreover, the same publication reported that BAG3 polymorphisms are also associated with sporadic forms of the disease together with HSPB7 locus.[13]

In muscle cells, BAG3 cooperates with the molecular chaperones Hsc70 and HspB8 to induce the degradation of mechanically damaged cytoskeleton components in lysosomes. This process is called chaperone-assisted selective autophagy and is essential for maintaining muscle activity in flies, mice and men.[8]

BAG3 is able to stimulate the expression of cytoskeleton proteins in response to mechanical tension by activating the transcription regulators YAP1 and WWTR1.[9] BAG3 balances protein synthesis and protein degradation under mechanical stress.

Interactions

[edit]

PLCG1 has been shown to interact with:

References

[edit]
  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000151929 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000030847 – 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. ^ Takayama S, Xie Z, Reed JC (Jan 1999). "An evolutionarily conserved family of Hsp70/Hsc70 molecular chaperone regulators". The Journal of Biological Chemistry. 274 (2): 781–6. doi:10.1074/jbc.274.2.781. PMID 9873016.
  6. ^ Carra S, Seguin SJ, Landry J (Feb 2008). "HspB8 and Bag3: a new chaperone complex targeting misfolded proteins to macroautophagy". Autophagy. 4 (2): 237–9. doi:10.4161/auto.5407. PMID 18094623.
  7. ^ a b "Entrez Gene: BAG3 BCL2-associated athanogene 3".
  8. ^ a b Arndt V, Dick N, Tawo R, Dreiseidler M, Wenzel D, Hesse M, Fürst DO, Saftig P, Saint R, Fleischmann BK, Hoch M, Höhfeld J (Jan 2010). "Chaperone-assisted selective autophagy is essential for muscle maintenance". Current Biology. 20 (2): 143–8. doi:10.1016/j.cub.2009.11.022. PMID 20060297. S2CID 8885338.
  9. ^ a b Ulbricht A, Eppler FJ, Tapia VE, van der Ven PF, Hampe N, Hersch N, Vakeel P, Stadel D, Haas A, Saftig P, Behrends C, Fürst DO, Volkmer R, Hoffmann B, Kolanus W, Höhfeld J (Mar 2013). "Cellular mechanotransduction relies on tension-induced and chaperone-assisted autophagy". Current Biology. 23 (5): 430–5. doi:10.1016/j.cub.2013.01.064. PMID 23434281.
  10. ^ Gamerdinger M, Hajieva P, Kaya AM, Wolfrum U, Hartl FU, Behl C. 2009" EMBO J 28(7) 889-901. Protein quality control during aging involves recruitment of the macroautophagy pathway by BAG3
  11. ^ Physorg:Old Cells Work Differently
  12. ^ Norton N, Li D, Rieder MJ, Siegfried JD, Rampersaud E, Züchner S, Mangos S, Gonzalez-Quintana J, Wang L, McGee S, Reiser J, Martin E, Nickerson DA, Hershberger RE (Mar 2011). "Genome-wide studies of copy number variation and exome sequencing identify rare variants in BAG3 as a cause of dilated cardiomyopathy". American Journal of Human Genetics. 88 (3): 273–82. doi:10.1016/j.ajhg.2011.01.016. PMC 3059419. PMID 21353195.
  13. ^ Villard E, Perret C, Gary F, Proust C, Dilanian G, Hengstenberg C, Ruppert V, Arbustini E, Wichter T, Germain M, Dubourg O, Tavazzi L, Aumont MC, DeGroote P, Fauchier L, Trochu JN, Gibelin P, Aupetit JF, Stark K, Erdmann J, Hetzer R, Roberts AM, Barton PJ, Regitz-Zagrosek V, Aslam U, Duboscq-Bidot L, Meyborg M, Maisch B, Madeira H, Waldenström A, Galve E, Cleland JG, Dorent R, Roizes G, Zeller T, Blankenberg S, Goodall AH, Cook S, Tregouet DA, Tiret L, Isnard R, Komajda M, Charron P, Cambien F (May 2011). "A genome-wide association study identifies two loci associated with heart failure due to dilated cardiomyopathy". European Heart Journal. 32 (9): 1065–76. doi:10.1093/eurheartj/ehr105. PMC 3086901. PMID 21459883.
  14. ^ Doong H, Price J, Kim YS, Gasbarre C, Probst J, Liotta LA, Blanchette J, Rizzo K, Kohn E (September 2000). "CAIR-1/BAG-3 forms an EGF-regulated ternary complex with phospholipase C-gamma and Hsp70/Hsc70". Oncogene. 19 (38): 4385–95. doi:10.1038/sj.onc.1203797. PMID 10980614.
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