This is the Rubicon homology domain (RH) characterised at the C-terminal of Rubicon, PLEKHM1 and Pacer, proteins that modulate late steps in autophagy [[cite:PUB00100995],[cite:PUB00100997]]. Rubicon (RUBCN) negatively regulates autophagy and endolysosomal trafficking by inhibiting PI3K complex II (PI3KC3-C2), which impairs autophagosome maturation process. PLEKHM1 is an adapter protein that regulates Rab7-dependent and HOPS complex-dependent fusion events in the endolysosomal system and couples autophagic and the endocytic trafficking pathways [[cite:PUB00100999],[cite:PUB00100998]]. On the other hand, Pacer positively regulates autophagy, promoting autophagosome maturation by facilitating the biogenesis of phosphatidylinositol 3-phosphate (PtdIns3P) in late steps of autophagy; it antagonises RUBCN [[cite:PUB00101000]]. This domain contains nine conserved cysteines and one conserved histidine, which have been predicted to bind divalent zinc cations being required for Rubicon and PLEKHM1 to interact with Rab7.
","llm":false,"checked":false,"updated":false}],"wikipedia":[{"title":"Rubicon_homology_domain","extract":"The Rubicon homology domain is an evolutionarily conserved protein domain of approximately 250 amino acids that mediates protein–protein interaction. RH domains are present in several human proteins involved in regulation of autophagy and endosomal trafficking. While not all RH domains have been characterized, those of human Rubicon and PLEKHM1 mediate interaction with the small GTPase Rab7, which is found on late endosomes and autophagosomes.
","thumbnail":null}],"literature":{"PUB00100995":{"PMID":32632011,"ISBN":null,"volume":"117","issue":"29","year":2020,"title":"Structural basis for autophagy inhibition by the human Rubicon-Rab7 complex.","URL":null,"raw_pages":"17003-17010","medline_journal":"Proc Natl Acad Sci U S A","ISO_journal":"Proc Natl Acad Sci U S A","authors":["Bhargava HK","Tabata K","Byck JM","Hamasaki M","Farrell DP","Anishchenko I","DiMaio F","Im YJ","Yoshimori T","Hurley JH."],"DOI_URL":null},"PUB00100998":{"PMID":28325809,"ISBN":null,"volume":"216","issue":"4","year":2017,"title":"The Rab7 effector PLEKHM1 binds Arl8b to promote cargo traffic to lysosomes.","URL":null,"raw_pages":"1051-1070","medline_journal":"J Cell Biol","ISO_journal":"J Cell Biol","authors":["Marwaha R","Arya SB","Jagga D","Kaur H","Tuli A","Sharma M."],"DOI_URL":null},"PUB00101000":{"PMID":30704899,"ISBN":null,"volume":"73","issue":"4","year":2019,"title":"Pacer Is a Mediator of mTORC1 and GSK3-TIP60 Signaling in Regulation of Autophagosome Maturation and Lipid Metabolism.","URL":null,"raw_pages":"788-802.e7","medline_journal":"Mol Cell","ISO_journal":"Mol Cell","authors":["Cheng X","Ma X","Zhu Q","Song D","Ding X","Li L","Jiang X","Wang X","Tian R","Su H","Shen Z","Chen S","Liu T","Gong W","Liu W","Sun Q."],"DOI_URL":null},"PUB00100999":{"PMID":25498145,"ISBN":null,"volume":"57","issue":"1","year":2015,"title":"PLEKHM1 regulates autophagosome-lysosome fusion through HOPS complex and LC3/GABARAP proteins.","URL":null,"raw_pages":"39-54","medline_journal":"Mol Cell","ISO_journal":"Mol Cell","authors":["McEwan DG","Popovic D","Gubas A","Terawaki S","Suzuki H","Stadel D","Coxon FP","Miranda de Stegmann D","Bhogaraju S","Maddi K","Kirchof A","Gatti E","Helfrich MH","Wakatsuki S","Behrends C","Pierre P","Dikic I."],"DOI_URL":null},"PUB00100997":{"PMID":30581147,"ISBN":null,"volume":"73","issue":"2","year":2019,"title":"Bidirectional Control of Autophagy by BECN1 BARA Domain Dynamics.","URL":null,"raw_pages":"339-353.e6","medline_journal":"Mol Cell","ISO_journal":"Mol Cell","authors":["Chang C","Young LN","Morris KL","von Bulow S","Schoneberg J","Yamamoto-Imoto H","Oe Y","Yamamoto K","Nakamura S","Stjepanovic G","Hummer G","Yoshimori T","Hurley JH."],"DOI_URL":null}},"set_info":{"accession":"CL0229","name":"RING"},"overlaps_with":null,"counters":{"subfamilies":0,"domain_architectures":123,"interactions":0,"matches":8152,"pathways":0,"proteins":8015,"proteomes":1750,"sets":1,"structural_models":{"alphafold":6861},"structures":1,"taxa":5484},"entry_annotations":{"hmm":0,"logo":0,"alignment:seed":91,"alignment:full":6301},"cross_references":{},"is_llm":false,"is_reviewed_llm":false,"is_updated_llm":false,"representative_structure":null}}