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References from Intramembrane proteolysis: principles of substrate recognition and membrane protein fate. Local targets link to admitted publications; unresolved targets remain external evidence.
Intramembrane proteolysis at a glance: from signalling to protein degradation
10.1242/jcs.217745 · 2019 · External reference
The role of SPP/SPPL intramembrane proteases in membrane protein homeostasis
10.1111/febs.16941 · 2024 · External reference
Presenilin, γ-secretase, and the search for pathogenic triggers of Alzheimer’s disease
10.1021/acs.biochem.4c00830 · 2025 · External reference
From mechanism to substratome: unraveling mysteries of γ-secretase
10.1016/j.jbc.2026.113287 · 2026 · External reference
Transmembrane segment proteases
10.1007/bf01282993 · 1999 · External reference
Regulated intramembrane proteolysis: a control mechanism conserved from bacteria to humans
10.1016/s0092-8674(00)80675-3 · 2000 · External reference
Crystal structure of a rhomboid family intramembrane protease
10.1038/nature05255 · 2006 · External reference
Structural biology of intramembrane proteases: mechanistic insights from rhomboid and S2P to γ-secretase
10.1016/j.sbi.2015.12.008 · 2016 · External reference
The role of presenilin cofactors in the gamma-secretase complex
10.1038/nature01506 · 2003 · External reference
Gamma-secretase is a membrane protein complex comprised of presenilin, nicastrin, Aph-1, and Pen-2
10.1073/pnas.1037392100 · 2003 · External reference
Identification of signal peptide peptidase, a presenilin-type aspartic protease
10.1126/science.1070925 · 2002 · External reference
Identification of a novel family of presenilin homologues
10.1093/hmg/11.9.1037 · 2002 · External reference
Mitochondrial membrane remodelling regulated by a conserved rhomboid protease
10.1038/nature01633 · 2003 · External reference
Diverse substrate recognition mechanisms for rhomboids; thrombomodulin is cleaved by mammalian rhomboids
2004 · External reference
Functional and evolutionary implications of enhanced genomic analysis of rhomboid intramembrane proteases
10.1101/gr.6425307 · 2007 · External reference
Structural analysis of a rhomboid family intramembrane protease reveals a gating mechanism for substrate entry
10.1038/nsmb1179 · 2006 · External reference
Architectural and thermodynamic principles underlying intramembrane protease function
10.1038/nchembio.1021 · 2012 · External reference
Substrate binding and specificity of rhomboid intramembrane protease revealed by substrate-peptide complex structures
10.15252/embj.201489367 · 2014 · External reference
Structure and dynamics of the rhomboid protease GlpG in liposomes studied by solid-state NMR
10.1021/jacs.9b08952 · 2019 · External reference
Rhomboid intramembrane protease YqgP licenses bacterial membrane protein quality control as adaptor of FtsH AAA protease
10.15252/embj.2019102935 · 2020 · External reference
Enzymatic analysis of a rhomboid intramembrane protease implicates transmembrane helix 5 as the lateral substrate gate
10.1073/pnas.0700814104 · 2007 · External reference
Ten catalytic snapshots of rhomboid intramembrane proteolysis from gate opening to peptide release
10.1038/s41594-019-0296-9 · 2019 · External reference
The opening dynamics of the lateral gate regulates the activity of rhomboid proteases
10.1126/sciadv.adh3858 · 2023 · External reference
General and modular strategy for designing potent, selective, and pharmacologically compliant inhibitors of rhomboid proteases
10.1016/j.chembiol.2017.09.007 · 2017 · External reference
Dimeric architecture and membrane thinning govern substrate recognition by human signal peptide peptidase
2026 · External reference
Substrate engagement by the intramembrane metalloprotease SpoIVFB
10.1038/s41467-024-52634-6 · 2024 · External reference
Sequence-specific intramembrane proteolysis: identification of a recognition motif in rhomboid substrates
10.1016/j.molcel.2009.11.006 · 2009 · External reference
Ubiquitin-dependent intramembrane rhomboid protease promotes ERAD of membrane proteins
10.1016/j.molcel.2012.06.008 · 2012 · External reference
Rhomboid protease RHBDL4 promotes retrotranslocation of aggregation-prone proteins for degradation
10.1016/j.celrep.2022.111175 · 2022 · External reference
Mechanism-based traps enable protease and hydrolase substrate discovery
10.1038/s41586-022-04414-9 · 2022 · External reference
Conformational selection mechanism of rhomboid-catalyzed intramembrane proteolysis revealed by solid-state NMR
10.1021/jacs.5c09134 · 2025 · External reference
Conformational flexibility of transmembrane helices: how it works and where it matters
10.1021/acs.chemrev.5c00581 · 2026 · External reference
Conformational surveillance of Orai1 by a rhomboid intramembrane protease prevents inappropriate CRAC channel activation
10.1016/j.molcel.2021.10.025 · 2021 · External reference
Structural basis of Notch recognition by human γ-secretase
10.1038/s41586-018-0813-8 · 2019 · External reference
Recognition of the amyloid precursor protein by human γ-secretase
10.1126/science.aaw0930 · 2019 · External reference
Molecular mechanism of substrate recognition and cleavage by human γ-secretase
10.1126/science.adn5820 · 2024 · External reference
Structural insights into human signal peptide peptidase
10.1073/pnas.2528340122 · 2025 · External reference
Cryo-EM structure of the bacterial intramembrane metalloprotease RseP in the substrate-bound state
10.1126/sciadv.adu0925 · 2025 · External reference
Roles of the membrane-reentrant β-hairpin-like loop of RseP protease in selective substrate cleavage
10.7554/elife.08928 · 2015 · External reference
Features of Pro- σK important for cleavage by SpoIVFB, an intramembrane metalloprotease
10.1128/jb.00229-13 · 2013 · External reference
Requirements for signal peptide peptidase-catalyzed intramembrane proteolysis
10.1016/s1097-2765(02)00655-x · 2002 · External reference
Substrate specificity of rhomboid intramembrane proteases is governed by helix-breaking residues in the substrate transmembrane domain
10.1016/s1097-2765(03)00181-3 · 2003 · External reference
Asparagine-proline sequence within membrane-spanning segment of SREBP triggers intramembrane cleavage by site-2 protease
10.1073/pnas.97.10.5123 · 2000 · External reference
Cooperation of N- and C-terminal substrate transmembrane domain segments in intramembrane proteolysis by γ-secretase
10.1038/s42003-023-04470-5 · 2023 · External reference
The metastable XBP1u transmembrane domain defines determinants for intramembrane proteolysis by signal peptide peptidase
10.1016/j.celrep.2019.02.057 · 2019 · External reference
Non-canonical shedding of TNFα by SPPL2a is determined by the conformational flexibility of its transmembrane helix
10.1016/j.isci.2020.101775 · 2020 · External reference
Mammalian EGF receptor activation by the rhomboid protease RHBDL2
10.1038/embor.2011.50 · 2011 · External reference
Cleavage of mitochondrial homeostasis regulator PGAM5 by the intramembrane protease PARL is governed by transmembrane helix dynamics and oligomeric state
10.1016/j.jbc.2022.102321 · 2022 · External reference
Rhomboid protease dynamics and lipid interactions
10.1016/j.str.2008.12.017 · 2009 · External reference
Rhomboid-catalyzed intramembrane proteolysis requires hydrophobic matching with the surrounding lipid bilayer
10.1126/sciadv.abq8303 · 2022 · External reference
Evaluating the impact of the membrane thickness on the function of the intramembrane protease GlpG
10.1016/j.bpj.2024.10.019 · 2024 · External reference
The TRC8 ubiquitin ligase is sterol regulated and interacts with lipid and protein biosynthetic pathways
10.1158/1541-7786.mcr-08-0491 · 2010 · External reference
Intramembrane protease SPP defines a cholesterol-regulated abundance control of the mevalonate pathway enzyme squalene synthase
10.1016/j.jbc.2024.105644 · 2024 · External reference
Direct and potent regulation of gamma-secretase by its lipid microenvironment
10.1074/jbc.m801925200 · 2008 · External reference
Generation of Alzheimer disease-associated amyloid β42/43 peptide by γ-secretase can be inhibited directly by modulation of membrane thickness
10.1074/jbc.m112.356659 · 2012 · External reference
Effects of membrane lipids on the activity and processivity of purified γ-secretase
10.1021/bi300303g · 2012 · External reference
Simulating the γ-secretase enzyme: recent advances and future directions
10.1016/j.biochi.2018.01.007 · 2018 · External reference
Membrane cholesterol as regulator of human rhomboid protease RHBDL4
10.1074/jbc.ra118.002640 · 2018 · External reference
Rhomboid protease RHBDL4/RHBDD1 cleaves SREBP-1c at endoplasmic reticulum monitoring and regulating fatty acids
10.1093/pnasnexus/pgad351 · 2023 · External reference
Engineering cardiolipin binding to an artificial membrane protein reveals determinants for lipid-mediated stabilization
10.7554/elife.104237 · 2025 · External reference
Insights into the catalytic properties of the mitochondrial rhomboid protease PARL
10.1016/j.jbc.2021.100383 · 2021 · External reference
Complementation cloning of S2P, a gene encoding a putative metalloprotease required for intramembrane cleavage of SREBPs
10.1016/s1097-2765(00)80006-4 · 1997 · External reference
PARL partitions the lipid transfer protein STARD7 between the cytosol and mitochondria
10.15252/embj.201797909 · 2018 · External reference
RHBDL2 drives lipid metabolic reprogramming in osteosarcoma via USP3-mediated deubiquitination of PPT1
10.1038/s41419-026-08788-w · 2026 · External reference
The complex life of rhomboid pseudoproteases
10.1111/febs.15548 · 2020 · External reference
Tumor necrosis factor signaling requires iRhom2 to promote trafficking and activation of TACE
10.1126/science.1214400 · 2012 · External reference
Cryo-EM reveals that iRhom2 restrains ADAM17 protease activity to control the release of growth factor and inflammatory signals
10.1016/j.molcel.2024.04.025 · 2024 · External reference
Structural insights into the activation and inhibition of the ADAM17-iRhom2 complex
10.1073/pnas.2500732122 · 2025 · External reference
A sterol-binding pocket in iRhom1 underlies paralog-specific regulation of the sheddase ADAM17
2026 · External reference
Function of the p97–Ufd1–Npl4 complex in retrotranslocation from the ER to the cytosol: dual recognition of nonubiquitinated polypeptide segments and polyubiquitin chains
10.1083/jcb.200302169 · 2003 · External reference
SEL1L–HRD1–mediated ERAD in mammals
10.1038/s41556-025-01690-1 · 2025 · External reference
Defining human ERAD networks through an integrative mapping strategy
10.1038/ncb2383 · 2011 · External reference
Interaction mapping of endoplasmic reticulum ubiquitin ligases identifies modulators of innate immune signalling
10.7554/elife.57306 · 2020 · External reference
Sterol-induced degradation of HMG CoA reductase depends on interplay of two Insigs and two ubiquitin ligases, gp78 and Trc8
10.1073/pnas.1112831108 · 2011 · External reference
Structural basis of ER-associated protein degradation mediated by the Hrd1 ubiquitin ligase complex
10.1126/science.aaz2449 · 2020 · External reference
The cryo-EM structure of the human ERAD retrotranslocation complex
10.1126/sciadv.adi5656 · 2023 · External reference
Cryo-EM structure of the human Derlin-1/p97 complex reveals a hexameric channel in ERAD
10.1038/s42003-025-08880-5 · 2025 · External reference
Structural insights into the human HRD1 ubiquitin ligase complex
10.1038/s41467-025-61143-z · 2025 · External reference
Functional interaction between SEL-10, an F-box protein, and the nuclear form of activated Notch1 receptor
10.1074/jbc.m101343200 · 2001 · External reference
The TRC8 E3 ligase ubiquitinates MHC class I molecules before dislocation from the ER
10.1083/jcb.200906110 · 2009 · External reference
Signal peptide peptidase functions in ERAD to cleave the unfolded protein response regulator XBP1u
10.15252/embj.201488208 · 2014 · External reference
The yeast ER-intramembrane protease Ypf1 refines nutrient sensing by regulating transporter abundance
10.1016/j.molcel.2014.10.012 · 2014 · External reference
MARCH6 and TRC8 facilitate the quality control of cytosolic and tail-anchored proteins
10.15252/embr.201745603 · 2018 · External reference
EGAD! There is an ERAD doppelganger in the Golgi
10.15252/embj.2019102679 · 2019 · External reference
Mitochondrial quality control via organelle and protein degradation
10.1093/jb/mvad106 · 2024 · External reference
Derlin-1 is a rhomboid pseudoprotease required for the dislocation of mutant α-1 antitrypsin from the endoplasmic reticulum
10.1038/nsmb.2111 · 2011 · External reference
Derlin rhomboid pseudoproteases employ substrate engagement and lipid distortion to enable the retrotranslocation of ERAD membrane substrates
10.1016/j.celrep.2021.109840 · 2021 · External reference
Function of site-2 proteases in bacteria and bacterial pathogens
10.1016/j.bbamem.2013.04.019 · 2013 · External reference
Regulated intracellular ligand transport and proteolysis control EGF signal activation in Drosophila
10.1016/s0092-8674(01)00526-8 · 2001 · External reference
ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs
10.1016/s1097-2765(00)00133-7 · 2000 · External reference
Gamma-secretase: proteasome of the membrane?
10.1038/nrm1406 · 2004 · External reference
Bacterial rhomboid proteases mediate quality control of orphan membrane proteins
10.15252/embj.2019102922 · 2020 · External reference
Rhomboid protease RHBDL2 is a calcium-activated suppressor of EGFR signalling in keratinocytes
2026 · External reference
Cleavage by signal peptide peptidase is required for the degradation of selected tail-anchored proteins
10.1083/jcb.201312009 · 2014 · External reference
Signal peptide peptidase-like proteases OsSPPL1 and OsSPPL2 facilitate ER-associated protein degradation in rice
10.1038/s41467-026-72830-w · 2026 · External reference
RHBDL4-triggered downregulation of COPII adaptor protein TMED7 suppresses TLR4-mediated inflammatory signaling
10.1038/s41467-024-45615-2 · 2024 · External reference
Proteolytic remodeling of cargo receptor networks by RHBDL4 tunes secretory pathway flux
2026 · External reference
Yeast SREBP cleavage activation requires the Golgi Dsc E3 ligase complex
10.1016/j.molcel.2011.02.035 · 2011 · External reference
Endosome and Golgi-associated degradation (EGAD) of membrane proteins regulates sphingolipid metabolism
10.15252/embj.2018101433 · 2019 · External reference
The Dsc ubiquitin ligase complex identifies transmembrane degrons to degrade orphaned proteins at the Golgi
10.1038/s41467-024-53676-6 · 2024 · External reference
Selective proteasomal degradation from the Golgi apparatus membrane
2026 · External reference
K48-ubiquitin-dependent proteases cut-up post-ER proteins
10.1038/s41467-026-68367-7 · 2026 · External reference
Identification of Rbd2 as a candidate protease for sterol regulatory element binding protein (SREBP) cleavage in fission yeast
10.1016/j.bbrc.2015.10.165 · 2015 · External reference
A Golgi rhomboid protease Rbd2 recruits Cdc48 to cleave yeast SREBP
10.15252/embj.201693923 · 2016 · External reference
Maintenance of organellar protein homeostasis by ER-associated degradation and related mechanisms
10.1016/j.molcel.2021.05.004 · 2021 · External reference
Rhomboid protease GlpG regulates type 1 pili quality control and virulence in pathogenic E. coli
10.1038/s41467-025-67697-2 · 2025 · External reference
Signal peptide peptidase promotes tumor progression via facilitating FKBP8 degradation
10.1038/s41388-018-0539-y · 2018 · External reference
Mitophagy in the pathogenesis and management of disease
10.1038/s41422-025-01203-7 · 2026 · External reference
Holding out for a model: rhomboid superfamily in vertebrate development and disease
10.1002/jcp.70094 · 2025 · External reference
Structural basis of γ-secretase inhibition and modulation by small molecule drugs
10.1016/j.cell.2020.11.049 · 2021 · External reference
