MARCHF6
entrez
10299
canonical
uniprot
O60337
canonical
ensembl
ENSG00000145495
resolver
ensp
ENSP00000274140
resolver
ensp
ENSP00000414643
resolver
ensp
ENSP00000424512
resolver
ensp
ENSP00000425930
resolver
ensp
ENSP00000660773
resolver
ensp
ENSP00000707211
resolver
ensp
ENSP00000797260
resolver
genesymbol
MARCHF6
resolver
genesymbol_syn
KIAA0597
resolver
genesymbol_syn
MARCH6
resolver
genesymbol_syn
RNF176
resolver
genesymbol_syn
TEB4
resolver
hgnc
HGNC:30550
resolver
uniprot
A5PKZ4
resolver
uniprot
B4DKJ2
resolver
uniprot
B4DT33
resolver
uniprot
D3DTC8
resolver
uniprot
O14670
resolver
uniprot
Q86X77
resolver
uniprot_entry
MARH6_HUMAN
resolver
uniprot_sec
A5PKZ4
resolver
uniprot_sec
B4DKJ2
resolver
uniprot_sec
B4DT33
resolver
uniprot_sec
D3DTC8
resolver
uniprot_sec
O14670
resolver
uniprot_sec
Q86X77
resolver
amino_acid_sequence
MDTAEEDICRVCRSEGTPEKPLYHPCVCTGSIKFIHQECLVQWLKHSRKEYCELCKHRFAFTPIYSPDMPSRLPIQDIFAGLVTSIGTAIRYWFHYTLVAFAWLGVVPLTACRIYKCLFTGSVSSLLTLPLDMLSTENLLADCLQGCFVVTCTLCAFISLVWLREQIVHGGAPIWLEHAAPPFNAAGHHQNEAPAGGNGAENVAADQPANPPAENAVVGENPDAQDDQAEEEEEDNEEEDDAGVEDAADANNGAQDDMNWNALEWDRAAEELTWERMLGLDGSLVFLEHVFWVVSLNTLFILVFAFCPYHIGHFSLVGLGFEEHVQASHFEGLITTIVGYILLAITLIICHGLATLVKFHRSRRLLGVCYIVVKVSLLVVVEIGVFPLICGWWLDICSLEMFDATLKDRELSFQSAPGTTMFLHWLVGMVYVFYFASFILLLREVLRPGVLWFLRNLNDPDFNPVQEMIHLPIYRHLRRFILSVIVFGSIVLLMLWLPIRIIKSVLPNFLPYNVMLYSDAPVSELSLELLLLQVVLPALLEQGHTRQWLKGLVRAWTVTAGYLLDLHSYLLGDQEENENSANQQVNNNQHARNNNAIPVVGEGLHAAHQAILQQGGPVGFQPYRRPLNFPLRIFLLIVFMCITLLIASLICLTLPVFAGRWLMSFWTGTAKIHELYTAACGLYVCWLTIRAVTVMVAWMPQGRRVIFQKVKEWSLMIMKTLIVAVLLAGVVPLLLGLLFELVIVAPLRVPLDQTPLFYPWQDWALGVLHAKIIAAITLMGPQWWLKTVIEQVYANGIRNIDLHYIVRKLAAPVISVLLLSLCVPYVIASGVVPLLGVTAEMQNLVHRRIYPFLLMVVVLMAILSFQVRQFKRLYEHIKNDKYLVGQRLVNYERKSGKQGSSPPPPQSSQE
uniprot
proteins
disease_involvement
DISEASE: Epilepsy, familial adult myoclonic, 3 (FAME3) [MIM:613608]: A form of familial myoclonic epilepsy, a neurologic disorder characterized by cortical hand tremors, myoclonic jerks and occasional generalized or focal seizures with a non-progressive or very slowly progressive disease course. Usually, myoclonic tremor is the presenting symptom, characterized by tremulous finger movements and myoclonic jerks of the limbs increased by action and posture. In a minority of patients, seizures are the presenting symptom. Some patients exhibit mild cognitive impairment. FAME3 inheritance is autosomal dominant. {ECO:0000269|PubMed:31664039}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
2.3.2.27
uniprot
proteins
function
FUNCTION: 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). {ECO:0000250|UniProtKB:Q6ZQ89, ECO:0000269|PubMed:15673284, ECO:0000269|PubMed:19651899, ECO:0000269|PubMed:24449766, ECO:0000269|PubMed:25088257, ECO:0000269|PubMed:29519897, ECO:0000269|PubMed:30425097, ECO:0000269|PubMed:31904814, ECO:0000269|PubMed:35941365, ECO:0000269|PubMed:36958722, ECO:0000269|PubMed:39216628}.
uniprot
proteins
mass_dalton
102545
uniprot
proteins
mutagenesis
MUTAGEN 9; /note="C->A: Abolished auto-ubiquitination. Loss of ubiquitin ligase activity."; /evidence="ECO:0000269|PubMed:15673284, ECO:0000269|PubMed:24449766, ECO:0000269|PubMed:29519897, ECO:0000269|PubMed:30425097, ECO:0000269|PubMed:35941365"; MUTAGEN 571; /note="L->A: Complete loss of Ac/N-degron recognition."; /evidence="ECO:0000269|PubMed:39216628"; MUTAGEN 885; /note="G->A: Does not restore the degradation of PLIN2 in MARCHF6-knockout cells."; /evidence="ECO:0000269|PubMed:35941365"; MUTAGEN 888; /note="L->A: Does not restore the degradation of PLIN2 in MARCHF6-knockout cells."; /evidence="ECO:0000269|PubMed:35941365
uniprot
proteins
pathway_participation
PATHWAY: Protein modification; protein ubiquitination. {ECO:0000269|PubMed:15673284}.
uniprot
proteins
post_translational_modification
PTM: Auto-ubiquitinated, which results in proteasomal degradation (PubMed:15673284). Deubiquitinated by USP19; protecting MARCHF6 from p97-mediated proteasomal degradation. {ECO:0000269|PubMed:15673284}.
uniprot
proteins
pubmed
11641273
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15372022
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15673284
uniprot
proteins
pubmed
16373356
uniprot
proteins
pubmed
19651899
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
24449766
uniprot
proteins
pubmed
25088257
uniprot
proteins
pubmed
29519897
uniprot
proteins
pubmed
30425097
uniprot
proteins
pubmed
31664039
uniprot
proteins
pubmed
31904814
uniprot
proteins
pubmed
35941365
uniprot
proteins
pubmed
36958722
uniprot
proteins
pubmed
39216628
uniprot
proteins
pubmed
9628581
uniprot
proteins
sequence_length
910
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000269|PubMed:15673284}; Multi-pass membrane protein {ECO:0000269|PubMed:15673284}.
uniprot
proteins
transmembrane_region
TRANSMEM 92..112; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 143..163; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 284..304; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 337..357; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 377..397; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 422..442; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 481..501; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 520..540; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 633..653; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 679..699; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 722..742; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 765..785; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 816..836; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 849..869; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins