Homologous Superfamily

MIF4G-like domain superfamily (IPR016021)

Short name: MIF4-like_sf

Overlapping entries


This superfamily represents an MIF4G-like domain. MIF4G domains share a common structure but can differ in sequence. The MIF4G domain is a structural motif with an ARM (Armadillo) repeat-type fold, consisting of a 2-layer alpha/alpha right-handed superhelix. Family members contain two or more structurally similar domains of this fold connected by unstructured linkers; this entry covers types 1, 2 and 3 MIF4G-like domains. MIF4G domains are found in several proteins involved in RNA metabolism, including eIF4G (eukaryotic initiation factor 4-gamma), eIF-2b (translation initiation factor), UPF2 (regulator of nonsense transcripts 2), and nuclear cap-binding proteins (CBP80, CBC1, NCBP1), although the sequence identity between them may be low [PMID: 10958635].

The nuclear cap-binding complex (CBC) is a heterodimer. Human CBC consists of a large CBP80 subunit and a small CBP20 subunit, the latter being critical for cap binding. CBP80 contains three MIF4G domains connected with long linkers, while CBP20 has an RNP (ribonucleoprotein)-type domain that associates with domains 2 and 3 of CBP80 [PMID: 11545740]. The complex binds to 5'-cap of eukaryotic RNA polymerase II transcripts, such as mRNA and U snRNA. The binding is important for several mRNA nuclear maturation steps and for nonsense-mediated decay. It is also essential for nuclear export of U snRNAs in metazoans [PMID: 16043498].

Eukaryotic translation initiation factor 4 gamma (eIF4G) plays a critical role in protein expression, and is at the centre of a complex regulatory network. Together with the cap-binding protein eIF4E, it recruits the small ribosomal subunit to the 5'-end of mRNA and promotes the assembly of a functional translation initiation complex, which scans along the mRNA to the translation start codon. The activity of eIF4G in translation initiation could be regulated through intra- and inter-protein interactions involving the ARM repeats [PMID: 16156639]. In eIF4G, the MIF4G domain binds eIF4A, eIF3, RNA and DNA.

Nonsense-mediated mRNA decay (NMD) in eukaryotes involves UPF1, UPF2 and UPF3 to accelerate the decay rate of two unique classes of transcripts: (1) nonsense mRNAs that arise through errors in gene expression, and (2) naturally occurring transcripts that lack coding errors but have built-in features that target them for accelerated decay (error-free mRNAs). NMD can trigger decay during any round of translation and can target CBC-bound or eIF-4E-bound transcripts [PMID: 16043493]. UPF2 contains MIF4G domains, while UPF3 contains an RNP domain [PMID: 15004547].

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.