BioPAX pathway converted from "AKT phosphorylates MKRN1" in the Reactome database. AKT phosphorylates MKRN1 AKT phosphorylates MKRN1 AKT1 (and possibly AKT2 and AKT3), activated in response to EGF treatment, phosphorylates MKRN1, an E3 ubiquitin ligase, on serine residue S109. AKT-mediated phosphorylation results in stabilization of MKRN1, protecting it from ubiquitination and proteasome-mediated degradation (Lee et al. 2015). Authored: Carracedo, Arkaitz, 2016-08-11 Authored: Salmena, Leonardo, 2016-08-11 Authored: Orlic-Milacic, Marija, 2016-11-16 Edited: Orlic-Milacic, Marija, 2017-05-09 Reactome DB_ID: 976042 1 cytosol GO 0005829 UniProt:Q9UHC7 MKRN1 MKRN1 MKRN1 RNF61 FUNCTION E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins. These substrates include FILIP1, p53/TP53, CDKN1A and TERT. Keeps cells alive by suppressing p53/TP53 under normal conditions, but stimulates apoptosis by repressing CDKN1A under stress conditions. Acts as a negative regulator of telomerase. Has negative and positive effects on RNA polymerase II-dependent transcription.PATHWAY Protein modification; protein ubiquitination.SUBUNIT Interacts with p53/TP53 and CDKN1A. Interacts with TERT, modulating telomere length homeostasis.TISSUE SPECIFICITY Ubiquitous.INDUCTION Frequently induced in esophageal squamous cell carcinoma (SCC) tissues.PTM Auto-ubiquitinated; which leads to proteasomal degradation. Reactome Homo sapiens NCBI Taxonomy 9606 UniProt Q9UHC7 Chain Coordinates 1 EQUAL 482 EQUAL Reactome DB_ID: 113592 1 ATP(4-) [ChEBI:30616] ATP(4-) Adenosine 5'-triphosphate atp ATP ChEBI 30616 Reactome DB_ID: 8948758 1 O-phospho-L-serine at 109 109 EQUAL O-phospho-L-serine [MOD:00046] 1 EQUAL 482 EQUAL Reactome DB_ID: 29370 1 ADP(3-) [ChEBI:456216] ADP(3-) ADP trianion 5'-O-[(phosphonatooxy)phosphinato]adenosine ADP ChEBI 456216 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Converted from EntitySet in Reactome Reactome DB_ID: 202074 p-T,p-S-AKT [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity p-T308,S473-AKT1 [cytosol] UniProt P31749 GO 0004674 GO molecular function Reactome Database ID Release 83 198368 Database identifier. Use this URL to connect to the web page of this instance in Reactome: Reactome Database ID Release 83 8948757 Database identifier. Use this URL to connect to the web page of this instance in Reactome: Reactome R-HSA-8948757 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: 26183061 Pubmed 2015 PI3K/AKT activation induces PTEN ubiquitination and destabilization accelerating tumourigenesis Lee, Min-Sik Jeong, Man-Hyung Lee, Hyun-Woo Han, Hyun-Ji Ko, Aram Hewitt, SM Kim, Jae-Hoon Chun, Kyung-Hee Chung, Joon-Yong Lee, Cheolju Cho, Hanbyoul Song, Jaewhan Nat Commun 6:7769 GO 0043491 GO biological process