PLEKHM1 explained

Pleckstrin homology domain-containing family M member 1 also known as PLEKHM1 is a protein that in humans is encoded by the PLEKHM1 gene.^{[1] [2]}

Function

PLEKHM1 may have critical function in vesicular transport in osteoclasts.^[3]

PLEKHM1 contains a C-terminal Rubicon Homology (RH) domain, which mediates interaction with small GTPase Rab7.^{[4] [5]} This domain is shared with family RH domain containing family members Rubicon and Pacer, which are autophagy regulators.^{[6] [7]}

Clinical significance

Mutations in the PLEKHM1 gene are associated with osteopetrosis OPTB6.^[3]

Further reading

• Stelzl U, Worm U, Lalowski M, etal . A human protein-protein interaction network: a resource for annotating the proteome. . Cell . 122 . 6 . 957–68 . 2005 . 16169070 . 10.1016/j.cell.2005.08.029 . 11858/00-001M-0000-0010-8592-0 . 8235923 . free .
• Hartel-Schenk S, Gratchev A, Hanski ML, etal . Novel adapter protein AP162 connects a sialyl-Le(x)-positive mucin with an apoptotic signal transduction pathway. . Glycoconj. J. . 18 . 11–12 . 915–23 . 2001. 12820725 . 10.1023/A:1022256610674 . 6993267 .
• Del Fattore A, Fornari R, Van Wesenbeeck L, etal . A new heterozygous mutation (R714C) of the osteopetrosis gene, pleckstrin homolog domain containing family M (with run domain) member 1 (PLEKHM1), impairs vesicular acidification and increases TRACP secretion in osteoclasts. . J. Bone Miner. Res. . 23 . 3 . 380–91 . 2008 . 17997709 . 10.1359/jbmr.071107 . 34037255 . free .
• Edwards TL, Scott WK, Almonte C, etal . Genome-Wide Association Study Confirms SNPs in SNCA and the MAPT Region as Common Risk Factors for Parkinson Disease. . Annals of Human Genetics . 74. 2. 97–109 . 2010 . 20070850 . 10.1111/j.1469-1809.2009.00560.x . 2853717 .
• Kimura K, Wakamatsu A, Suzuki Y, etal . Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. . Genome Res. . 16 . 1 . 55–65 . 2006 . 16344560 . 10.1101/gr.4039406 . 1356129 .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2002 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Van Wesenbeeck L, Odgren PR, Coxon FP, etal . Involvement of PLEKHM1 in osteoclastic vesicular transport and osteopetrosis in incisors absent rats and humans. . J. Clin. Invest. . 117 . 4 . 919–30 . 2007 . 17404618 . 10.1172/JCI30328 . 1838941 .

Notes and References

1. Nagase T, Ishikawa K, Nakajima D, Ohira M, Seki N, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O . Prediction of the coding sequences of unidentified human genes. VII. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro . DNA Res. . 4 . 2 . 141–50 . April 1997 . 9205841 . 10.1093/dnares/4.2.141. free .
2. Hartel-Schenk S, Gratchev A, Hanski ML, Ogorek D, Trendelenburg G, Hummel M, Höpfner M, Scherübl H, Zeitz M, Hanski C . Novel adapter protein AP162 connects a sialyl-Le(x)-positive mucin with an apoptotic signal transduction pathway . Glycoconj. J. . 18 . 11–12 . 915–23 . 2001 . 12820725 . 10.1023/A:1022256610674. 6993267 .
3. van Wesenbeeck L, Odgren PR, Mackay CA, Van Hul W . Localization of the gene causing the osteopetrotic phenotype in the incisors absent (ia) rat on chromosome 10q32.1 . J. Bone Miner. Res. . 19 . 2 . 183–9 . February 2004 . 14969387 . 10.1359/jbmr.2004.19.2.183 . 22195601 . free .
4. Web site: PLEKHM1 - Pleckstrin homology domain-containing family M member 1 - Homo sapiens (Human) - PLEKHM1 gene & protein . 2022-05-31 . www.uniprot.org . en.
5. Bhargava . Hersh K. . Tabata . Keisuke . Byck . Jordan M. . Hamasaki . Maho . Farrell . Daniel P. . Anishchenko . Ivan . DiMaio . Frank . Im . Young Jun . Yoshimori . Tamotsu . Hurley . James H. . 2020-07-21 . Structural basis for autophagy inhibition by the human Rubicon-Rab7 complex . Proceedings of the National Academy of Sciences of the United States of America . 117 . 29 . 17003–17010 . 10.1073/pnas.2008030117 . 1091-6490 . 7382272 . 32632011. 2020PNAS..11717003B . free .
6. Beltran . S. . Nassif . M. . Vicencio . E. . Arcos . J. . Labrador . L. . Cortes . B. I. . Cortez . C. . Bergmann . C. A. . Espinoza . S. . Hernandez . M. F. . Matamala . J. M. . 2019-03-27 . Network approach identifies Pacer as an autophagy protein involved in ALS pathogenesis . Molecular Neurodegeneration . 14 . 1 . 14 . 10.1186/s13024-019-0313-9 . 1750-1326 . 6437924 . 30917850 . free .
7. Tabata . Keisuke . Matsunaga . Kohichi . Sakane . Ayuko . Sasaki . Takuya . Noda . Takeshi . Yoshimori . Tamotsu . December 2010 . Rubicon and PLEKHM1 negatively regulate the endocytic/autophagic pathway via a novel Rab7-binding domain . Molecular Biology of the Cell . 21 . 23 . 4162–4172 . 10.1091/mbc.E10-06-0495 . 1939-4586 . 2993745 . 20943950.