E3 ubiquitin-protein ligase MARCHF6 (EC 2.3.2.27) (Doa10 homolog) (Membrane-associated RING finger protein 6) (Membrane-associated RING-CH protein VI) (MARCH-VI) (Protein TEB-4) (RING finger protein 176) (RING-type E3 ubiquitin transferase MARCHF6)
1_MDTAE 6_ EDICR 11_ VCRSE 16_ GTPEK 21_ PLYHP 26_ CVCTG 31_ SIKFI 36_ HQECL 41_ VQWLK 46_ HSRKE 51_ YCELC 56_ KHRFA 61_ FTPIY 66_ SPDMP 71_ SRLPI 76_ QDIFA 81_ GLVTS 86_ IGTAI 91_ RYWFH 96_ YTLVA 101_ FAWLG 106_ VVPLT 111_ ACRIY 116_ KCLFT 121_ GSVSS 126_ LLTLP 131_ LDMLS 136_ TENLL 141_ ADCLQ 146_ GCFVV 151_ TCTLC 156_ AFISL 161_ VWLRE 166_ QIVHG 171_ GAPIW 176_ LEHAA 181_ PPFNA 186_ AGHHQ 191_ NEAPA 196_ GGNGA 201_ ENVAA 206_ DQPAN 211_ PPAEN 216_ AVVGE 221_ NPDAQ 226_ DDQAE 231_ EEEED 236_ NEEED 241_ DAGVE 246_ DAADA 251_ NNGAQ 256_ DDMNW 261_ NALEW 266_ DRAAE 271_ ELTWE 276_ RMLGL 281_ DGSLV 286_ FLEHV 291_ FWVVS 296_ LNTLF 301_ ILVFA 306_ FCPYH 311_ IGHFS 316_ LVGLG 321_ FEEHV 326_ QASHF 331_ EGLIT 336_ TIVGY 341_ ILLAI 346_ TLIIC 351_ HGLAT 356_ LVKFH 361_ RSRRL 366_ LGVCY 371_ IVVKV 376_ SLLVV 381_ VEIGV 386_ FPLIC 391_ GWWLD 396_ ICSLE 401_ MFDAT 406_ LKDRE 411_ LSFQS 416_ APGTT 421_ MFLHW 426_ LVGMV 431_ YVFYF 436_ ASFIL 441_ LLREV 446_ LRPGV 451_ LWFLR 456_ NLNDP 461_ DFNPV 466_ QEMIH 471_ LPIYR 476_ HLRRF 481_ ILSVI 486_ VFGSI 491_ VLLML 496_ WLPIR 501_ IIKSV 506_ LPNFL 511_ PYNVM 516_ LYSDA 521_ PVSEL 526_ SLELL 531_ LLQVV 536_ LPALL 541_ EQGHT 546_ RQWLK 551_ GLVRA 556_ WTVTA 561_ GYLLD 566_ LHSYL 571_ LGDQE 576_ ENENS 581_ ANQQV 586_ NNNQH 591_ ARNNN 596_ AIPVV 601_ GEGLH 606_ AAHQA 611_ ILQQG 616_ GPVGF 621_ QPYRR 626_ PLNFP 631_ LRIFL 636_ LIVFM 641_ CITLL 646_ IASLI 651_ CLTLP 656_ VFAGR 661_ WLMSF 666_ WTGTA 671_ KIHEL 676_ YTAAC 681_ GLYVC 686_ WLTIR 691_ AVTVM 696_ VAWMP 701_ QGRRV 706_ IFQKV 711_ KEWSL 716_ MIMKT 721_ LIVAV 726_ LLAGV 731_ VPLLL 736_ GLLFE 741_ LVIVA 746_ PLRVP 751_ LDQTP 756_ LFYPW 761_ QDWAL 766_ GVLHA 771_ KIIAA 776_ ITLMG 781_ PQWWL 786_ KTVIE 791_ QVYAN 796_ GIRNI 801_ DLHYI 806_ VRKLA 811_ APVIS 816_ VLLLS 821_ LCVPY 826_ VIASG 831_ VVPLL 836_ GVTAE 841_ MQNLV 846_ HRRIY 851_ PFLLM 856_ VVVLM 861_ AILSF 866_ QVRQF 871_ KRLYE 876_ HIKND 881_ KYLVG 886_ QRLVN 891_ YERKS 896_ GKQGS 901_SPPPP
1: Endoplasmic reticulum membrane-associated E3 ubiquitin ligase that plays a critical role in mitigating endoplasmic reticulum stress, the regulation of cholesterol and lipid homeostasis, and ferroptosis (PubMed:25088257, PubMed:35941365, PubMed:39216628). Acts as a pivotal component of both the Ac/N-degron pathway (targeting the N-terminal acetyl group of substrates) and the ER-associated protein degradation-cytosol (ERAD-C) pathway (targeting misfolded substrates) (PubMed:30425097, PubMed:35941365). For instance, mediates the degradation of Ac/N-degron-bearing proteins such as the G-protein regulator RGS2 and the lipid droplet protein PLIN2 (PubMed:39216628). Suppresses endoplasmic reticulum stress and ferroptosis through cytosolic POMC degradation (By similarity). Prevents ferroptosis by acting as a NADPH sensor during lipid peroxidation through its C-terminal regulatory region (PubMed:35941365). Facilitates also the degradation of selected endoplasmic reticulum proteins by associating with signal peptide peptidase for the turnover of endogenous tail-anchored proteins (PubMed:29519897). Promotes ubiquitination of DIO2, leading to its degradation (PubMed:19651899). By ubiquitinating and thereby modulating the stability of many proteins of the cholesterol pathway including SQLE, CYP51A1, CYP11A1 and HMGCR, acts as a crucial post-translational regulator of cholesterol synthesis (PubMed:24449766, PubMed:31904814, PubMed:36958722)