PLEKHM1

PLEKHM1
Identifiers
Aliases	PLEKHM1, AP162, B2, OPTB6, pleckstrin homology and RUN domain containing M1, OPTA3
External IDs	OMIM: 611466; MGI: 2443207; 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 cell; ; skin of leg; ; vagina; ; minor salivary glands; ; right hemisphere of cerebellum; ; sural nerve; ; granulocyte; ; ectocervix;
	Top expressed in
	granulocyte; ; zygote; ; stroma of bone marrow; ; mesenteric lymph nodes; ; blood; ; transitional epithelium of urinary bladder; ; decidua; ; interventricular septum; ; right lung; ; otolith organ;
	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
Databases	NCBI: entry; OMA: entry
	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

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]

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, et al. (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 Research. 4 (2): 141–150. doi:10.1093/dnares/4.2.141. PMID 9205841.
↑ Hartel-Schenk S, Gratchev A, Hanski ML, Ogorek D, Trendelenburg G, Hummel M, et al. (2001). "Novel adapter protein AP162 connects a sialyl-Le(x)-positive mucin with an apoptotic signal transduction pathway". Glycoconjugate Journal. 18 (11–12): 915–923. 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". Journal of Bone and Mineral Research. 19 (2): 183–189. 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". UniProt. Retrieved 2022-05-31.
1 2 Bhargava HK, Tabata K, Byck JM, Hamasaki M, Farrell DP, Anishchenko I, et al. (July 2020). "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. PMC 7382272. PMID 32632011.
↑ Beltran S, Nassif M, Vicencio E, Arcos J, Labrador L, Cortes BI, et al. (March 2019). "Network approach identifies Pacer as an autophagy protein involved in ALS pathogenesis". Molecular Neurodegeneration. 14 (1) 14. doi:10.1186/s13024-019-0313-9. PMC 6437924. PMID 30917850.
↑ Tabata K, Matsunaga K, Sakane A, Sasaki T, Noda T, Yoshimori T (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. PMC 2993745. PMID 20943950.

Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck FH, Goehler H, et al. (September 2005). "A human protein-protein interaction network: a resource for annotating the proteome". Cell. 122 (6): 957–968. doi:10.1016/j.cell.2005.08.029. hdl:11858/00-001M-0000-0010-8592-0. PMID 16169070. S2CID 8235923.
Del Fattore A, Fornari R, Van Wesenbeeck L, de Freitas F, Timmermans JP, Peruzzi B, et al. (March 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". Journal of Bone and Mineral Research. 23 (3): 380–391. doi:10.1359/jbmr.071107. PMID 17997709. S2CID 34037255.
Edwards TL, Scott WK, Almonte C, Burt A, Powell EH, Beecham GW, et al. (March 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, Ota T, Nishikawa T, Yamashita R, et al. (January 2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Research. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.
Van Wesenbeeck L, Odgren PR, Coxon FP, Frattini A, Moens P, Perdu B, et al. (April 2007). "Involvement of PLEKHM1 in osteoclastic vesicular transport and osteopetrosis in incisors absent rats and humans". The Journal of Clinical Investigation. 117 (4): 919–930. doi:10.1172/JCI30328. PMC 1838941. PMID 17404618.

[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.

[Nagase_1997-5] Nagase T, Ishikawa K, Nakajima D, Ohira M, Seki N, Miyajima N, et al. (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 Research. 4 (2): 141–150. doi:10.1093/dnares/4.2.141. PMID 9205841.

[Hartel-Schenk_2001-6] Hartel-Schenk S, Gratchev A, Hanski ML, Ogorek D, Trendelenburg G, Hummel M, et al. (2001). "Novel adapter protein AP162 connects a sialyl-Le(x)-positive mucin with an apoptotic signal transduction pathway". Glycoconjugate Journal. 18 (11–12): 915–923. doi:10.1023/A:1022256610674. PMID 12820725. S2CID 6993267.

[van_2004-7] 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". Journal of Bone and Mineral Research. 19 (2): 183–189. 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". UniProt. Retrieved 2022-05-31.

[Bhargava_2020-9] 1 2 Bhargava HK, Tabata K, Byck JM, Hamasaki M, Farrell DP, Anishchenko I, et al. (July 2020). "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. PMC 7382272. PMID 32632011.

[10] Beltran S, Nassif M, Vicencio E, Arcos J, Labrador L, Cortes BI, et al. (March 2019). "Network approach identifies Pacer as an autophagy protein involved in ALS pathogenesis". Molecular Neurodegeneration. 14 (1) 14. doi:10.1186/s13024-019-0313-9. PMC 6437924. PMID 30917850.

[11] Tabata K, Matsunaga K, Sakane A, Sasaki T, Noda T, Yoshimori T (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. PMC 2993745. PMID 20943950.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

[11]

Function

Clinical significance

References

Further reading