PLEKHM1

{{Short description|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.{{cite journal | vauthors = Nagase T, Ishikawa K, Nakajima D, Ohira M, Seki N, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O | title = 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 | journal = DNA Res. | volume = 4 | issue = 2 | pages = 141–50 |date=April 1997 | pmid = 9205841 | doi = 10.1093/dnares/4.2.141| doi-access = free }}{{cite journal | vauthors = Hartel-Schenk S, Gratchev A, Hanski ML, Ogorek D, Trendelenburg G, Hummel M, Höpfner M, Scherübl H, Zeitz M, Hanski C | title = Novel adapter protein AP162 connects a sialyl-Le(x)-positive mucin with an apoptotic signal transduction pathway | journal = Glycoconj. J. | volume = 18 | issue = 11–12 | pages = 915–23 | year = 2001 | pmid = 12820725 | doi = 10.1023/A:1022256610674| s2cid = 6993267 | url = http://www.kluweronline.com/art.pdf?issn=0282-0080&volume=18&page=915 }}

Function

PLEKHM1 may have critical function in vesicular transport in osteoclasts.{{cite journal | vauthors = van Wesenbeeck L, Odgren PR, Mackay CA, Van Hul W | title = Localization of the gene causing the osteopetrotic phenotype in the incisors absent (ia) rat on chromosome 10q32.1 | journal = J. Bone Miner. Res. | volume = 19 | issue = 2 | pages = 183–9 |date=February 2004 | pmid = 14969387 | doi = 10.1359/jbmr.2004.19.2.183 | s2cid = 22195601 | doi-access = free }}

PLEKHM1 contains a C-terminal Rubicon Homology (RH) domain, which mediates interaction with small GTPase Rab7.{{Cite web |title=PLEKHM1 - Pleckstrin homology domain-containing family M member 1 - Homo sapiens (Human) - PLEKHM1 gene & protein |url=https://www.uniprot.org/uniprot/Q9Y4G2 |access-date=2022-05-31 |website=www.uniprot.org |language=en}}{{Cite journal |last1=Bhargava |first1=Hersh K. |last2=Tabata |first2=Keisuke |last3=Byck |first3=Jordan M. |last4=Hamasaki |first4=Maho |last5=Farrell |first5=Daniel P. |last6=Anishchenko |first6=Ivan |last7=DiMaio |first7=Frank |last8=Im |first8=Young Jun |last9=Yoshimori |first9=Tamotsu |last10=Hurley |first10=James H. |date=2020-07-21 |title=Structural basis for autophagy inhibition by the human Rubicon-Rab7 complex |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=117 |issue=29 |pages=17003–17010 |doi=10.1073/pnas.2008030117 |issn=1091-6490 |pmc=7382272 |pmid=32632011|bibcode=2020PNAS..11717003B |doi-access=free }} This domain is shared with family RH domain containing family members Rubicon and Pacer, which are autophagy regulators.{{Cite journal |last1=Beltran |first1=S. |last2=Nassif |first2=M. |last3=Vicencio |first3=E. |last4=Arcos |first4=J. |last5=Labrador |first5=L. |last6=Cortes |first6=B. I. |last7=Cortez |first7=C. |last8=Bergmann |first8=C. A. |last9=Espinoza |first9=S. |last10=Hernandez |first10=M. F. |last11=Matamala |first11=J. M. |date=2019-03-27 |title=Network approach identifies Pacer as an autophagy protein involved in ALS pathogenesis |journal=Molecular Neurodegeneration |volume=14 |issue=1 |pages=14 |doi=10.1186/s13024-019-0313-9 |issn=1750-1326 |pmc=6437924 |pmid=30917850 |doi-access=free }}{{Cite journal |last1=Tabata |first1=Keisuke |last2=Matsunaga |first2=Kohichi |last3=Sakane |first3=Ayuko |last4=Sasaki |first4=Takuya |last5=Noda |first5=Takeshi |last6=Yoshimori |first6=Tamotsu |date=December 2010 |title=Rubicon and PLEKHM1 negatively regulate the endocytic/autophagic pathway via a novel Rab7-binding domain |journal=Molecular Biology of the Cell |volume=21 |issue=23 |pages=4162–4172 |doi=10.1091/mbc.E10-06-0495 |issn=1939-4586 |pmc=2993745 |pmid=20943950}}

Clinical significance

Mutations in the PLEKHM1 gene are associated with osteopetrosis OPTB6.

PLEKHM1

Function

Clinical significance

References

Further reading