| Structural highlights
Function
[GOLP3_HUMAN] Mediates the cis and medial Golgi localization of mannosyltransferases through direct binding of their cytosolic domains. Involved in modulation of mTOR signaling. Involved in the regulation of mitochondrial lipids, leading to increase of mitochondrial mass. Potential oncogene.[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Targeting and retention of resident integral membrane proteins of the Golgi apparatus underly the function of the Golgi in glycoprotein and glycolipid processing and sorting. In yeast, steady-state Golgi localization of multiple mannosyltransferases requires recognition of their cytosolic domains by the peripheral Golgi membrane protein Vps74, an orthologue of human GOLPH3/GPP34/GMx33/MIDAS (mitochondrial DNA absence sensitive factor). We show that targeting of Vps74 and GOLPH3 to the Golgi apparatus requires ongoing synthesis of phosphatidylinositol (PtdIns) 4-phosphate (PtdIns4P) by the Pik1 PtdIns 4-kinase and that modulation of the levels and cellular location of PtdIns4P leads to mislocalization of these proteins. Vps74 and GOLPH3 bind specifically to PtdIns4P, and a sulfate ion in a crystal structure of GOLPH3 indicates a possible phosphoinositide-binding site that is conserved in Vps74. Alterations in this site abolish phosphoinositide binding in vitro and Vps74 function in vivo. These results implicate Pik1 signaling in retention of Golgi-resident proteins via Vps74 and show that GOLPH3 family proteins are effectors of Golgi PtdIns 4-kinases.
PtdIns4P recognition by Vps74/GOLPH3 links PtdIns 4-kinase signaling to retrograde Golgi trafficking.,Wood CS, Schmitz KR, Bessman NJ, Setty TG, Ferguson KM, Burd CG J Cell Biol. 2009 Dec 28;187(7):967-75. Epub 2009 Dec 21. PMID:20026658[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Nakashima-Kamimura N, Asoh S, Ishibashi Y, Mukai Y, Shidara Y, Oda H, Munakata K, Goto Y, Ohta S. MIDAS/GPP34, a nuclear gene product, regulates total mitochondrial mass in response to mitochondrial dysfunction. J Cell Sci. 2005 Nov 15;118(Pt 22):5357-67. Epub 2005 Nov 1. PMID:16263763 doi:http://dx.doi.org/10.1242/jcs.02645
- ↑ Scott KL, Kabbarah O, Liang MC, Ivanova E, Anagnostou V, Wu J, Dhakal S, Wu M, Chen S, Feinberg T, Huang J, Saci A, Widlund HR, Fisher DE, Xiao Y, Rimm DL, Protopopov A, Wong KK, Chin L. GOLPH3 modulates mTOR signalling and rapamycin sensitivity in cancer. Nature. 2009 Jun 25;459(7250):1085-90. doi: 10.1038/nature08109. PMID:19553991 doi:http://dx.doi.org/10.1038/nature08109
- ↑ Wood CS, Schmitz KR, Bessman NJ, Setty TG, Ferguson KM, Burd CG. PtdIns4P recognition by Vps74/GOLPH3 links PtdIns 4-kinase signaling to retrograde Golgi trafficking. J Cell Biol. 2009 Dec 28;187(7):967-75. Epub 2009 Dec 21. PMID:20026658 doi:10.1083/jcb.200909063
- ↑ Wood CS, Schmitz KR, Bessman NJ, Setty TG, Ferguson KM, Burd CG. PtdIns4P recognition by Vps74/GOLPH3 links PtdIns 4-kinase signaling to retrograde Golgi trafficking. J Cell Biol. 2009 Dec 28;187(7):967-75. Epub 2009 Dec 21. PMID:20026658 doi:10.1083/jcb.200909063
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