| Structural highlights
Disease
[PKHM1_HUMAN] Intermediate osteopetrosis. The disease is caused by mutations affecting the gene represented in this entry.
Function
[PKHM1_HUMAN] Proposed to act as a multivalent adapter protein that regulates Rab7-dependent and HOPS complex-dependent fusion events in the endolysosomal system and couples autophagic and the endocytic trafficking pathways. Required for late stages of endolysosomal maturation, facilitating both endocytosis-mediated degradation of growth factor receptors and autophagosome clearance. Seems to be involved in the terminal maturation of autophagosomes and to mediate autophagosome-lysosome fusion (PubMed:25498145). Involved in vesicular transport in the osteoclast (By similarity). May be involved in negative regulation of endocytic transport from early endosome to late endosome/lysosome implicating its association with Rab7 (PubMed:20943950). May have a role in sialyl-lex-mediated transduction of apoptotic signals (PubMed:12820725). In case of infection contributes to Salmonella typhimurium pathogenesis by supporting the integrity of the Salmonella-containing vacuole (SCV) probably in concert with the HOPS complex and Rab7 (PubMed:25500191).[UniProtKB:Q5PQS0][1] [2] [3] [4]
References
- ↑ Hartel-Schenk S, Gratchev A, Hanski ML, Ogorek D, Trendelenburg G, Hummel M, Hopfner M, Scherubl H, Zeitz M, Hanski C. Novel adapter protein AP162 connects a sialyl-Le(x)-positive mucin with an apoptotic signal transduction pathway. Glycoconj J. 2001 Nov-Dec;18(11-12):915-23. PMID:12820725
- ↑ Tabata K, Matsunaga K, Sakane A, Sasaki T, Noda T, Yoshimori T. Rubicon and PLEKHM1 negatively regulate the endocytic/autophagic pathway via a novel Rab7-binding domain. Mol Biol Cell. 2010 Dec;21(23):4162-72. doi: 10.1091/mbc.E10-06-0495. Epub 2010, Oct 13. PMID:20943950 doi:https://dx.doi.org/10.1091/mbc.E10-06-0495
- ↑ McEwan DG, Popovic D, Gubas A, Terawaki S, Suzuki H, Stadel D, Coxon FP, Miranda de Stegmann D, Bhogaraju S, Maddi K, Kirchof A, Gatti E, Helfrich MH, Wakatsuki S, Behrends C, Pierre P, Dikic I. PLEKHM1 Regulates Autophagosome-Lysosome Fusion through HOPS Complex and LC3/GABARAP Proteins. Mol Cell. 2015 Jan 8;57(1):39-54. doi: 10.1016/j.molcel.2014.11.006. Epub 2014, Dec 11. PMID:25498145 doi:https://dx.doi.org/10.1016/j.molcel.2014.11.006
- ↑ McEwan DG, Richter B, Claudi B, Wigge C, Wild P, Farhan H, McGourty K, Coxon FP, Franz-Wachtel M, Perdu B, Akutsu M, Habermann A, Kirchof A, Helfrich MH, Odgren PR, Van Hul W, Frangakis AS, Rajalingam K, Macek B, Holden DW, Bumann D, Dikic I. PLEKHM1 regulates Salmonella-containing vacuole biogenesis and infection. Cell Host Microbe. 2015 Jan 14;17(1):58-71. doi: 10.1016/j.chom.2014.11.011. Epub, 2014 Dec 11. PMID:25500191 doi:https://dx.doi.org/10.1016/j.chom.2014.11.011
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