Protein-coding gene in the species Homo sapiens
Pleckstrin homology domain-containing family M member 1 also known as PLEKHM1 is a protein that in humans is encoded by the PLEKHM1 gene .[5] [6]
Function PLEKHM1 may have critical function in vesicular transport in osteoclasts .[7]
PLEKHM1 contains a C-terminal Rubicon Homology (RH) domain , which mediates interaction with small GTPase Rab7 .[8] [9] Rubicon and Pacer , which are autophagy regulators.[10] [11] [9]
Clinical significance Mutations in the PLEKHM1 gene are associated with osteopetrosis OPTB6.[7]
References
^ a b c ENSG00000225190, ENSG00000276358 GRCh38: Ensembl release 89: ENSG00000277111, ENSG00000225190, ENSG00000276358 – Ensembl , May 2017^ a b c GRCm38: Ensembl release 89: ENSMUSG00000034247 – Ensembl , May 2017^ "Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ "Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ Nagase T, Ishikawa K, Nakajima D, Ohira M, Seki N, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (April 1997). "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. doi :10.1093/dnares/4.2.141 PMID 9205841 . ^ Hartel-Schenk S, Gratchev A, Hanski ML, Ogorek D, Trendelenburg G, Hummel M, Höpfner M, Scherübl H, Zeitz M, Hanski C (2001). "Novel adapter protein AP162 connects a sialyl-Le(x)-positive mucin with an apoptotic signal transduction pathway" (PDF) . Glycoconj. J . 18 (11–12): 915–23. doi :10.1023/A:1022256610674 . PMID 12820725 . S2CID 6993267 . ^ a b van Wesenbeeck L, Odgren PR, Mackay CA, Van Hul W (February 2004). "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. doi :10.1359/jbmr.2004.19.2.183 PMID 14969387 . S2CID 22195601 . ^ "PLEKHM1 - Pleckstrin homology domain-containing family M member 1 - Homo sapiens (Human) - PLEKHM1 gene & protein" . www.uniprot.org . Retrieved 2022-05-31 .^ a b 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. Bibcode :2020PNAS..11717003B . doi :10.1073/pnas.2008030117 ISSN 1091-6490 . PMC 7382272 PMID 32632011 . ^ 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. doi :10.1186/s13024-019-0313-9 ISSN 1750-1326 . PMC 6437924 PMID 30917850 . ^ 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. doi :10.1091/mbc.E10-06-0495 . ISSN 1939-4586 . PMC 2993745 PMID 20943950 .
Further reading
Stelzl U, Worm U, Lalowski M, et al. (2005). "A human protein-protein interaction network: a resource for annotating the proteome". Cell . 122 (6): 957–68. doi :10.1016/j.cell.2005.08.029 . hdl :11858/00-001M-0000-0010-8592-0 PMID 16169070 . S2CID 8235923 . Hartel-Schenk S, Gratchev A, Hanski ML, et al. (2001). "Novel adapter protein AP162 connects a sialyl-Le(x)-positive mucin with an apoptotic signal transduction pathway". Glycoconj. J . 18 (11–12): 915–23. doi :10.1023/A:1022256610674 . PMID 12820725 . S2CID 6993267 . Del Fattore A, Fornari R, Van Wesenbeeck L, et al. (2008). "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. doi :10.1359/jbmr.071107 PMID 17997709 . S2CID 34037255 . Edwards TL, Scott WK, Almonte C, et al. (2010). "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. doi :10.1111/j.1469-1809.2009.00560.x . PMC 2853717 PMID 20070850 . Kimura K, Wakamatsu A, Suzuki Y, et al. (2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes" . Genome Res . 16 (1): 55–65. doi :10.1101/gr.4039406 . PMC 1356129 PMID 16344560 . Strausberg RL, Feingold EA, Grouse LH, et al. (2002). "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. Bibcode :2002PNAS...9916899M . doi :10.1073/pnas.242603899 PMC 139241 PMID 12477932 . Van Wesenbeeck L, Odgren PR, Coxon FP, et al. (2007). "Involvement of PLEKHM1 in osteoclastic vesicular transport and osteopetrosis in incisors absent rats and humans" . J. Clin. Invest . 117 (4): 919–30. doi :10.1172/JCI30328 . PMC 1838941 PMID 17404618 .
