MARCH2

MARCH2 is a member of the MARCH family of membrane-bound E3 ubiquitin ligases. MARCH enzymes add ubiquitin to target lysines in substrate proteins, thereby signaling their vesicular transport between membrane compartments. MARCH2 reduces surface accumulation of several glycoproteins and appears to regulate early endosome-to-trans-Golgi network trafficking.

Full Name

membrane-associated ring finger (C3HC4) 2

Function

E3 ubiquitin-protein ligase that may mediate ubiquitination of TFRC and CD86, and promote their subsequent endocytosis and sorting to lysosomes via multivesicular bodies. 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 (PubMed:14722266, PubMed:16428329).

Together with GOPC/CAL mediates the ubiquitination and lysosomal degradation of CFTR (PubMed:23818989).

Ubiquitinates and therefore mediates the degradation of DLG1 (PubMed:17980554).

Regulates the intracellular trafficking and secretion of alpha1-antitrypsin/SERPINA1 and HP/haptoglobin via ubiquitination and degradation of the cargo receptor ERGIC3 (PubMed:31142615).

Negatively regulates the antiviral and antibacterial immune response by repression of the NF-kB and type 1 IFN signaling pathways, via MARCHF2-mediated K48-linked polyubiquitination of IKBKG/NEMO, resulting in its proteosomal degradation (PubMed:32935379).

May be involved in endosomal trafficking through interaction with STX6 (PubMed:15689499).

(Microbial infection) Positively regulates the degradation of Vesicular stomatitis virus (VSV) G protein via the lysosomal degradation pathway (PubMed:29573664).

Represses HIV-1 viral production and may inhibit the translocation of HIV-1 env to the cell surface, resulting in decreased viral cell-cell transmission (PubMed:29573664).

Biological Process

Antibacterial innate immune response Source: UniProtKB
Antiviral innate immune response Source: UniProtKB
Endocytosis Source: UniProtKB-KW
Positive regulation of lysosomal protein catabolic process Source: UniProtKB
Protein ubiquitination Source: UniProtKB
Suppression of viral release by host Source: UniProtKB

Cellular Location

Plasma membrane
Cell membrane
Endosome
Endosome membrane
Endoplasmic reticulum
Endoplasmic reticulum membrane
Cytoplasm and Cytosol
Cytoplasm
Lysosome
Lysosome membrane
Golgi apparatus
Golgi apparatus membrane