PLEKHM1

PLEKHM1
Identifiers
Aliases	PLEKHM1 , AP162, B2, OPTB6, pleckstrin homology and RUN domain containing M1, OPTA3
External IDs	OMIM: 611466 MGI: 2443207 HomoloGene: 8871 GeneCards: PLEKHM1
Gene location (Human)
Chr.	Chromosome 17 (human)
End	45,490,749 bp
Gene location (Mouse)
Chr.	Chromosome 11 (mouse)
End	103,303,513 bp
RNA expression pattern
	Top expressed in
	blood; ; bone marrow; ; bone marrow cells; ; vagina; ; minor salivary gland; ; sural nerve; ; monocyte; ; skin of abdomen; ; spleen; ; upper lobe of left lung;
	Top expressed in
	blood; ; interventricular septum; ; right lung; ; otolith organ; ; utricle; ; oocyte; ; subcutaneous adipose tissue; ; secondary oocyte; ; spleen; ; ileum;
	More reference expression data
	n/a
Gene ontology
Molecular function	metal ion binding ;
Cellular component	lysosomal membrane ; endosome membrane ; lysosome ; membrane ; cytoplasm ; endosome ; nucleolus ; intracellular membrane-bounded organelle ;
Biological process	autophagy ; protein transport ; intracellular signal transduction ; lysosome localization ; positive regulation of bone resorption ; positive regulation of ruffle assembly ;
	Sources:Amigo / QuickGO
Orthologs
	9842
	353047
	ENSG00000277111 ; ENSG00000225190 ; ENSG00000276358
	ENSMUSG00000034247
	Q9Y4G2
	Q7TSI1
	NM_014798 ; NM_001352825
	NM_183034
	NP_055613 ; NP_001339754
	NP_898855
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated December 04, 2023

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] This domain is shared with family RH domain containing family members Rubicon and Pacer, which are autophagy regulators.^[10]^[11]^[9]

Clinical significance

Mutations in the PLEKHM1 gene are associated with osteopetrosis OPTB6.^[7]

Related Research Articles

Tartrate-resistant acid phosphatase, also called acid phosphatase 5, tartrate resistant (ACP5), is a glycosylated monomeric metalloprotein enzyme expressed in mammals. It has a molecular weight of approximately 35kDa, a basic isoelectric point (7.6–9.5), and optimal activity in acidic conditions. TRAP is synthesized as latent proenzyme and activated by proteolytic cleavage and reduction. It is differentiated from other mammalian acid phosphatases by its resistance to inhibition by tartrate and by its molecular weight.

Ras-related protein Rab-7a is a protein that in humans is encoded by the RAB7A gene.

Dynamin-1 is a protein that in humans is encoded by the DNM1 gene.

Beclin-1 is a protein that in humans is encoded by the BECN1 gene. Beclin-1 is a mammalian ortholog of the yeast autophagy-related gene 6 (Atg6) and BEC-1 in the C. elegans nematode. This protein interacts with either BCL-2 or PI3k class III, playing a critical role in the regulation of both autophagy and cell death.

Chloride channel 7 alpha subunit also known as H⁺/Cl⁻ exchange transporter 7 is a protein that in humans is encoded by the CLCN7 gene. In melanocytic cells this gene is regulated by the Microphthalmia-associated transcription factor.

Autophagy related 12 is a protein that in humans is encoded by the ATG12 gene.

Pleckstrin homology domain-containing family A member 5 is a protein that in humans is encoded by the PLEKHA5 gene.

Cytohesin-3 is a protein that in humans is encoded by the CYTH3 gene.

Pleckstrin homology domain-containing family B member 2 is a protein that in humans is encoded by the PLEKHB2 gene.

Pleckstrin homology domain-containing family F member 2 is a protein that in humans is encoded by the PLEKHF2 gene.

FERM, RhoGEF and pleckstrin domain-containing protein 1 is a protein that in humans is encoded by the FARP1 gene.

Oxysterol-binding protein-related protein 1 is a protein that in humans is encoded by the OSBPL1A gene.

Diacylglycerol kinase theta is an enzyme that in humans is encoded by the DGKQ gene.

Pleckstrin homology domain-containing family A member 6 is a protein that in humans is encoded by the PLEKHA6 gene.

Cytohesin-4 is a protein that in humans is encoded by the CYTH4 gene.

Vesicular glutamate transporter 3 (VGLUT3) is a protein that in humans is encoded by the SLC17A8 gene.

Pleckstrin Homology domain containing Family M Member 3, or PLEKHM3, is the hypothetical protein that in humans is encoded by the PLEKHM3 gene. PLEKHM3 is also known as DAPR, and Pleckstrin Homology Domain Containing Family M, Member 1-like.

Pacer is a protein that in humans is encoded by the RUBCNL gene. Pacer has been shown to increase cellular autophagy through regulation of PI3KC3.

Rubicon is a protein that in humans is encoded by the RUBCN gene. Rubicon is one of the few known negative regulators of autophagy, a cellular process that degrades unnecessary or damaged cellular components. Rubicon is recruited to its sites of action through interaction with the small GTPase Rab7, and impairs the autophagosome-lysosome fusion step of autophagy through inhibition of PI3KC3-C2.

The Rubicon homology domain is an evolutionarily conserved protein domain of approximately 250 amino acids that mediates protein–protein interaction. RH domains are present in several human proteins involved in regulation of autophagy and endosomal trafficking. While not all RH domains have been characterized, those of human Rubicon and PLEKHM1 mediate interaction with the small GTPase Rab7, which is found on late endosomes and autophagosomes.

References

1 2 3 ENSG00000225190, ENSG00000276358 GRCh38: Ensembl release 89: ENSG00000277111, ENSG00000225190, ENSG00000276358 - Ensembl, May 2017
1 2 3 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.
1 2 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.
1 2 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.

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.

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[refGRCh38Ensembl-1] 1 2 3 ENSG00000225190, ENSG00000276358 GRCh38: Ensembl release 89: ENSG00000277111, ENSG00000225190, ENSG00000276358 - Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000034247 - 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.

[pmid9205841-5] 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.

[pmid12820725-6] 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.

[pmid14969387-7] 1 2 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.

[8] "PLEKHM1 - Pleckstrin homology domain-containing family M member 1 - Homo sapiens (Human) - PLEKHM1 gene & protein". www.uniprot.org. Retrieved 2022-05-31.

[:0-9] 1 2 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.

[10] 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.

[11] 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.

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PLEKHM1

Contents

Function

Clinical significance

Related Research Articles

References

Further reading