Pacer (protein) explained

Pacer (also known as Rubicon-like) is a protein that in humans is encoded by the RUBCNL gene.^[1] Pacer has been shown to increase cellular autophagy through regulation of PI3KC3.^[2]

Pacer contains a Rubicon homology (RH) domain at its C-terminus, which mediates binding to small GTPase Rab7 when Rab7 is phosphorylated following mitochondrial damage^[3] .^{[4] [5]} This domain is shared with RH domain containing family members Rubicon and PLEKHM1.^[6] Whereas Pacer appears to upregulate autophagic activity, Rubicon is a negative regulator of autophagy.

Further reading

• Ng D, Hu N, Hu Y, Wang C, Giffen C, Tang ZZ, Han XY, Yang HH, Lee MP, Goldstein AM, Taylor PR . Replication of a genome-wide case-control study of esophageal squamous cell carcinoma . International Journal of Cancer . 123 . 7 . 1610–1615 . October 2008 . 18649358 . 2552411 . 10.1002/ijc.23682 .
• Cronin S, Tomik B, Bradley DG, Slowik A, Hardiman O . Screening for replication of genome-wide SNP associations in sporadic ALS . European Journal of Human Genetics . 17 . 2 . 213–218 . February 2009 . 18987618 . 2986065 . 10.1038/ejhg.2008.194 .
• Yang N, Eijsink JJ, Lendvai A, Volders HH, Klip H, Buikema HJ, van Hemel BM, Schuuring E, van der Zee AG, Wisman GB . Methylation markers for CCNA1 and C13ORF18 are strongly associated with high-grade cervical intraepithelial neoplasia and cervical cancer in cervical scrapings . Cancer Epidemiology, Biomarkers & Prevention . 18 . 11 . 3000–3007 . November 2009 . 19843677 . 10.1158/1055-9965.EPI-09-0405 . free .
• Eijsink JJ, Lendvai Á, Deregowski V, Klip HG, Verpooten G, Dehaspe L, de Bock GH, Hollema H, van Criekinge W, Schuuring E, van der Zee AG, Wisman GB . A four-gene methylation marker panel as triage test in high-risk human papillomavirus positive patients . International Journal of Cancer . 130 . 8 . 1861–1869 . April 2012 . 21796628 . 10.1002/ijc.26326 . 35295117 . free .
• Huisman C, Wisman GB, Kazemier HG, van Vugt MA, van der Zee AG, Schuuring E, Rots MG . Functional validation of putative tumor suppressor gene C13ORF18 in cervical cancer by Artificial Transcription Factors . Molecular Oncology . 7 . 3 . 669–679 . June 2013 . 23522960 . 5528488 . 10.1016/j.molonc.2013.02.017 .

Notes and References

1. Web site: RUBCNL - Protein associated with UVRAG as autophagy enhancer - Homo sapiens (Human) - RUBCNL gene & protein . 2022-05-31 . www.uniprot.org . en.
2. Cheng X, Ma X, Ding X, Li L, Jiang X, Shen Z, Chen S, Liu W, Gong W, Sun Q . Pacer Mediates the Function of Class III PI3K and HOPS Complexes in Autophagosome Maturation by Engaging Stx17 . Molecular Cell . 65 . 6 . 1029–1043.e5 . March 2017 . 28306502 . 10.1016/j.molcel.2017.02.010 . free .
3. Tudorica DA, Basak B, Puerta Cordova AS, Khuu G, Rose K, Lazarou M, Holzbaur EL, Hurley JH . A RAB7A phosphoswitch coordinates Rubicon Homology protein regulation of Parkin-dependent mitophagy . The Journal of Cell Biology . 223 . 7 . July 2024 . 38728007 . 11090050 . 10.1083/jcb.202309015 .
4. Web site: RUBCNL - Protein associated with UVRAG as autophagy enhancer - Homo sapiens (Human) - RUBCNL gene & protein . 2022-05-31 . www.uniprot.org . en.
5. Bhargava HK, Tabata K, Byck JM, Hamasaki M, Farrell DP, Anishchenko I, DiMaio F, Im YJ, Yoshimori T, Hurley JH . 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 . July 2020 . 32632011 . 7382272 . 10.1073/pnas.2008030117 . free . 2020PNAS..11717003B .
6. Beltran S, Nassif M, Vicencio E, Arcos J, Labrador L, Cortes BI, Cortez C, Bergmann CA, Espinoza S, Hernandez MF, Matamala JM, Bargsted L, Matus S, Rojas-Rivera D, Bertrand MJ, Medinas DB, Hetz C, Manque PA, Woehlbier U . Network approach identifies Pacer as an autophagy protein involved in ALS pathogenesis . Molecular Neurodegeneration . 14 . 1 . 14 . March 2019 . 30917850 . 6437924 . 10.1186/s13024-019-0313-9 . free .