TCDB is operated by the Saier Lab Bioinformatics Group
TCIDNameDomainKingdom/PhylumProtein(s)
8.A.159.1.1









MARCH1 (MARCHF1; RNF171) of 189 aas and 2 TMSs near, but not at, the C-terninus. It is an E3 ubiquitin-protein ligase that mediates ubiquitination of the transferrin recpeotor (TFRC), CD86, FAS and MHC class II proteins, such as HLA-DR alpha and beta, and promotes their subsequent endocytosis and sorting to lysosomes via multivesicular bodies (Lapaque et al. 2009). By constitutively ubiquitinating MHC class II proteins in immature dendritic cells, it down-regulates their cell surface localizations, thus sequestering them in the intracellular endosomal system (De Gassart et al. 2008). It, and its orthologs, play roles in antiviral innate immunity (Zheng 2021) (see family description).

Eukaryota
Metazoa, Chordata
MARCH1 of Homo sapiens
8.A.159.1.2









MARCH6 of 910 aas and ~15 TMSs in a 3 + 6 + 6 TMS arrangement. It is a E3 ubiquitin-protein ligase that promotes 'Lys-48'-linked ubiquitination of target proteins, leading to their proteasomal degradation (Hassink et al. 2005). It promotes ubiquitination of DIO2, leading to its degradation (Zavacki et al. 2009) as well as of SQLE, leading to its degradation (Zelcer et al. 2014). 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. It may cooperate with UBE2G1 (Hassink et al. 2005). Some members of TC family 3.A.16 (i.e., 3.A.16.1.2 and 1.5) utilize homologues as part of a multicomponent system.  Doa10/MARCH6 architecture interconnects E3 ligase activity with lipid-binding transmembrane channel to regulate SQLE (Botsch et al. 2024).

Archaea
Euryarchaeota
MARCH6 of Homo sapiens
8.A.159.1.3









MARCH2 (MARCHII) of 246 aas and 2 TMSs, near the C-terminus of the protein. It is an E3 ubiquitin-protein ligase that may mediate ubiquitination of TFRC and CD86, and promote their subsequent endocytosis and sorting to lysosomes via multivesicular bodies (Nakamura et al. 2005). 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 and may be involved in endosomal trafficking through interaction with STX6 (Bartee et al. 2004).

Eukaryota
Metazoa, Chordata
MARCH2 of Homo sapiens
8.A.159.1.4









RING finger membrane protein of 1631 aas and 18 TMSs in an apparent 3 + 3 + 5 + 6 TMS arrangement.

Eukaryota
Fungi, Ascomycota
RING finger protein of Aspergillus sclerotialis
8.A.159.1.6









Uncharacterized protein of 423 aas and 4 C-terminal TMSs.

Eukaryota
Viridiplantae, Streptophyta
UP of Gossypium mustelinum
8.A.159.1.7









Uncharacterized protein of 629 aas and 3 C-terminal TMSs.

Eukaryota
Fungi, Mucoromycota
UP of Podila horticola
8.A.159.1.8









Uncharacterized protein of 265 aas and 2 C-terminal TMSs.

Eukaryota
Metazoa, Arthropoda
UP of Drosophila pseudoobscura
8.A.159.1.9









MARCH3, RNF173, MARCHF3, of 253 aas and 2 TMSs, close to each other and near the C-terminus of the protein.

Eukaryota
Metazoa, Chordata
MARCH3 of Homo sapiens
8.A.159.1.10









MIR2 (K5) of human herpesvirus 8 type P (isolate GK18) (HHV-8) (Kaposi's sarcoma-associated herpesvirus). E3 ubiquitin-protein ligase promotes ubiquitination and subsequent degradation of host MHC-I, CD86, ICAM1 and CD1D molecules, to prevent lysis of infected cells by cytotoxic T-lymphocytes and NK cell. It binds target molecules through transmembrane interactions. Different features of CD86 to downregulate surface expression are responsible for binding (Trenker et al. 2021).

 

Viruses
Heunggongvirae, Peploviricota
MIR2 of Herpies viruses
8.A.159.1.11









The E3 ubiquitin-protein ligase of 910 aas and 15 TMSs in a 3 + 6 + 6 TMS arrangement.  The last two 6 TMS units are probably duplicates of each other.  The ligase promotes 'Lys-48'-linked ubiquitination of target proteins, leading to their proteasomal degradation (Hassink et al. 2005).

Eukaryota
Metazoa, Chordata
E3 ubiquitin:protein liganse of Homo sapiens
8.A.159.2.1









Uncharacterized protein of 1102 aas and up to 11 TMSs, possibly in a 5 + 6 TMS arrangement.

Eukaryota
Euglenozoa
UP of Leishmania guyanensis
8.A.159.2.2









E3 ubiquitin-protein ligase, MARCH7 isoform X5, of 862 aas and possibly 3 C-terminal TMSs.

Eukaryota
Metazoa, Chordata
Protein liganse of Petromyzon marinus (sea lamprey)
8.A.159.3.1









Uncharacterized protein of 260 aas and 2 TMSs (C-terminal).

Eukaryota
Viridiplantae, Streptophyta
UP of Citrus sinensis
8.A.159.3.2









E3 ubiquitin-protein ligase MARCH2 of 207 aas and 2 C-terminal TMSs.

Eukaryota
Viridiplantae, Streptophyta
MARCH2 of Zea mays