MARCH6
This gene encodes a member of a family of membrane-associated E3 ubiquitin ligases containing RING-CH-type zinc finger motifs. Ubiquitination of type II deiodinase by the encoded protein is an important regulatory step in thyroid hormone signalling. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.
Full Name
membrane-associated ring finger (C3HC4) 6
Function
E3 ubiquitin-protein ligase that promotes 'Lys-48'-linked ubiquitination of target proteins, leading to their proteasomal degradation (PubMed:15673284).
Promotes ubiquitination of DIO2, leading to its degradation (PubMed:19651899).
Promotes ubiquitination of SQLE, leading to its degradation (PubMed:24449766).
E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfer the ubiquitin to targeted substrates. May cooperate with UBE2G1 (PubMed:15673284).
Biological Process
Endoplasmic reticulum mannose trimming Source: Reactome
ERAD pathway Source: ParkinsonsUK-UCL
Proteasomal protein catabolic process Source: ParkinsonsUK-UCL
Proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
Protein K48-linked ubiquitination Source: UniProtKB
Protein ubiquitination Source: UniProtKB
Ubiquitin-dependent ERAD pathway Source: GO_Central
Cellular Location
Endoplasmic reticulum membrane
Involvement in disease
Epilepsy, familial adult myoclonic, 3 (FAME3):
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.
Topology
Cytoplasmic: 1-91
Helical: 92-112
Extracellular: 113-142
Helical: 143-163
Cytoplasmic: 164-283
Helical: 284-304
Extracellular: 305-336
Helical: 337-357
Cytoplasmic: 358-376
Helical: 377-397
Extracellular: 398-421
Helical: 422-442
Cytoplasmic: 443-480
Helical: 481-501
Extracellular: 502-519
Helical: 520-540
Cytoplasmic: 541-632
Helical: 633-653
Extracellular: 654-678
Helical: 679-699
Cytoplasmic: 700-721
Helical: 722-742
Extracellular: 743-764
Helical: 765-785
Cytoplasmic: 786-815
Helical: 816-836
Extracellular: 837-848
Helical: 849-869
Cytoplasmic: 870-910
PTM
Auto-ubiquitinated, which results in proteasomal degradation.
Loading...
Datasheet