PROSITE documentation PDOC52085

HERC2-like domain profile

The HERC2-like domain, also called HERC2-like repeat, HERC2-related repeat, Mib repeat, Mib-like repeat or iron-sulfur cluster-dependent NCOA4-binding domain (INBD), is found in one to nine copies in the following proteins:

• Animal HERC2, an E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. HERC2 consists of three regulator of chromosome condensation 1-like domains (RLDs) each made of seven RCC1 repeats (see <PDOC00544>), a cytochrome-b5 like (cyt-b5) domain (see <PDOC00170>), a MIB/HERC2 domain (see <PDOC51416>), a Cullin-7- PARC-HERC2 (CPH) domain (see <PDOC52081>), a HERC2-like domain, a ZZ-type zinc finger (ZZ) domain (see <PDOC50135>), a down regulated in ovarian cancer (DOC) domain (see <PDOC51284>), and a C-terminal catalytic E3- enzymatic homologous to E6AP C-terminus (HECT) domain (see <PDOC50237>) [1].
• Animal Mind bomb (Mib) proteins, large multi-domain E3 ligases that promote ubiquitination of the cytoplasmic tails of Notch ligands. In addition to their role as Notch ligand effectors, Mib proteins have also been implicated as ubiquitin ligases for proteins involved in innate immunity, neuronal function, Wnt/β-catenin signaling, genomic stability, and cell death. Mib proteins are made of four contiguous structural elements: (i) an MZM region, which contains two Mib-Herc2 domains (see <PDOC51416>) flanking a ZZ zinc finger (ZZ) (see <PDOC50135>); (ii) a REP region, which includes two tandem repeats of HERC2-like domains; (iii) an ANK region, which spans nine ankyrin (ANK) repeats (see <PDOC50088>); and (iv) a RNG region, which contains two or three RING fingers (see (<PDOC00449>) [2].
• Arabidopsis thaliana KEG (for KEEP ON GOING), a RING E3 ligase required for abscisic acid (ABA) signaling and postgerminative growth of seedlings. It contains a RING finger (see <PDOC00449>), a kinase domain (see <PDOC00100>), nine ANK repeats (see <PDOC50088>) and twelve HERC2-like repeats [3,4].
• Arabidopsis thaliana KOC1, an integral chloroplast envelope kinase acting as a regulatory component of the plastid protein import machinery by phosphorylating import receptors (e.g. the A-domain of TOC159, TOC120 and TOC132). KOC1 contains a kinase domain (see <PDOC00100>), a HERC2-related region made of two HERC2-like domains and a predicted transmembrane helix [5].

HERC2-like domains have been shown to mediate a large range of protein:protein interactions [1,2,3,4].

The HERC2-like domain folds have a five-stranded anti-parallel twisted β sheet topology similar to that of SH3 domains, even though the two types of modules have no detectable sequence homology (see <PDB:4XI6>) [1,2].

The profile we developed covers the entire HERC2-like domain.