Protein-coding gene in the species Homo sapiens
RNF144A is an E3 ubiquitin ligase belonging to the RING-between RING (RBR) family of ubiquitin ligases , whose specific members have been shown to function as RING-HECT hybrid E3 ligases.[ 5] [ 6] [ 7] [ 8] [ 9] [ 10] [ 11] [ 12]
The biological functions of RNF144A is/are relatively unknown beyond its intrinsic enzymatic activity . Somatic mutations of RNF144A have been catalogued in cancer genetic databases in several primary human tumors , including breast , stomach , lymphoma , glioblastoma , uterine and lung cancers . Other members of the RBR family have been associated with neurological and immunological diseases, most notably parkin , HOIL-1L and HOIP(RNF31).[ 13] [ 14] [ 15] [ 16]
Current known substrates of RNF144A targeted for degradation are proteins involved in DNA repair , heatshock/chaperone function and signalling, consistent with the predominant association of this protein with cancer, and include (DNA-PKcs ), PARP1 , HSPA2 , BMI1 , and RAF1 .[ 17] [ 18] [ 19] [ 20] [ 21]
^ a b c GRCh38: Ensembl release 89: ENSG00000151692 – Ensembl , May 2017^ a b c GRCm38: Ensembl release 89: ENSMUSG00000020642 – 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 .^ Wenzel DM, Lissounov A, Brzovic PS, Klevit RE (June 2011). "UBCH7 reactivity profile reveals parkin and HHARI to be RING/HECT hybrids" . Nature . 474 (7349): 105–8. doi :10.1038/nature09966 . PMC 3444301 PMID 21532592 . ^ "RNF144A ring finger protein 144A [Homo sapiens (human)] - Gene - NCBI" . www.ncbi.nlm.nih.gov . National Center for Biotechnology Information , U.S. National Library of Medicine . Retrieved 2019-10-27 .^ "RNF144A - E3 ubiquitin-protein ligase RNF144A - Homo sapiens (Human) - RNF144A gene & protein" . www.uniprot.org . UniProt . Retrieved 2019-10-27 .^ Dove KK, Klevit RE (November 2017). "RING-Between-RING E3 Ligases: Emerging Themes amid the Variations" . Journal of Molecular Biology . 429 (22): 3363–3375. doi :10.1016/j.jmb.2017.08.008 . PMC 5675740 PMID 28827147 . ^ Spratt DE, Walden H, Shaw GS (March 2014). "RBR E3 ubiquitin ligases: new structures, new insights, new questions" . The Biochemical Journal . 458 (3): 421–37. doi :10.1042/BJ20140006 . PMC 3940038 PMID 24576094 . ^ Eisenhaber B, Chumak N, Eisenhaber F, Hauser MT (2007). "The ring between ring fingers (RBR) protein family" . Genome Biology . 8 (3): 209. doi :10.1186/gb-2007-8-3-209 PMC 1868946 PMID 17367545 . ^ Michel MA, Swatek KN, Hospenthal MK, Komander D (October 2017). "Ubiquitin Linkage-Specific Affimers Reveal Insights into K6-Linked Ubiquitin Signaling" . Molecular Cell . 68 (1): 233–246.e5. doi :10.1016/j.molcel.2017.08.020 . PMC 5640506 PMID 28943312 . ^ Ho SR, Lee YJ, Lin WC (September 2015). "Regulation of RNF144A E3 Ubiquitin Ligase Activity by Self-association through Its Transmembrane Domain" . The Journal of Biological Chemistry . 290 (38): 23026–38. doi :10.1074/jbc.M115.645499 PMC 4645615 PMID 26216882 . ^ Pickrell AM, Youle RJ (January 2015). "The roles of PINK1, parkin, and mitochondrial fidelity in Parkinson's disease" . Neuron . 85 (2): 257–73. doi :10.1016/j.neuron.2014.12.007 . PMC 4764997 PMID 25611507 . ^ Oda H, Beck DB, Kuehn HS, Sampaio Moura N, Hoffmann P, Ibarra M, et al. (2019-03-18). "Second Case of HOIP Deficiency Expands Clinical Features and Defines Inflammatory Transcriptome Regulated by LUBAC" . Frontiers in Immunology . 10 : 479. doi :10.3389/fimmu.2019.00479 PMC 6431612 PMID 30936877 . ^ Boisson B, Laplantine E, Dobbs K, Cobat A, Tarantino N, Hazen M, et al. (June 2015). "Human HOIP and LUBAC deficiency underlies autoinflammation, immunodeficiency, amylopectinosis, and lymphangiectasia" . The Journal of Experimental Medicine . 212 (6): 939–51. doi :10.1084/jem.20141130 . PMC 4451137 PMID 26008899 . ^ Boisson B, Laplantine E, Prando C, Giliani S, Israelsson E, Xu Z, et al. (December 2012). "Immunodeficiency, autoinflammation and amylopectinosis in humans with inherited HOIL-1 and LUBAC deficiency" . Nature Immunology . 13 (12): 1178–86. doi :10.1038/ni.2457 . PMC 3514453 PMID 23104095 . ^ Ho SR, Mahanic CS, Lee YJ, Lin WC (July 2014). "RNF144A, an E3 ubiquitin ligase for DNA-PKcs, promotes apoptosis during DNA damage" . Proceedings of the National Academy of Sciences of the United States of America . 111 (26): E2646-55. Bibcode :2014PNAS..111E2646H . doi :10.1073/pnas.1323107111 PMC 4084471 PMID 24979766 . ^ Zhang Y, Liao XH, Xie HY, Shao ZM, Li DQ (November 2017). "RBR-type E3 ubiquitin ligase RNF144A targets PARP1 for ubiquitin-dependent degradation and regulates PARP inhibitor sensitivity in breast cancer cells" . Oncotarget . 8 (55): 94505–94518. doi :10.18632/oncotarget.21784 . PMC 5706891 PMID 29212245 . ^ Yang YL, Zhang Y, Li DD, Zhang FL, Liu HY, Liao XH, et al. (August 2019). "RNF144A functions as a tumor suppressor in breast cancer through ubiquitin ligase activity-dependent regulation of stability and oncogenic functions of HSPA2" . Cell Death and Differentiation . 27 (3): 1105–1118. doi :10.1038/s41418-019-0400-z . PMC 7205990 PMID 31406303 . ^ Jin X, Kim LJ, Wu Q, Wallace LC, Prager BC, Sanvoranart T, et al. (November 2017). "Targeting glioma stem cells through combined BMI1 and EZH2 inhibition" . Nature Medicine . 23 (11): 1352–1361. doi :10.1038/nm.4415 . PMC 5679732 PMID 29035367 . ^ Afzali B, Kim S, West E, Nova-Lamperti E, Cheru N, Nagashima H, et al. (2019-09-26). "RNF144A shapes the hierarchy of cytokine signaling to provide protective immunity against influenza" . doi :10.1101/782680 
