Summary

MIF4G domain

MIF4G is named after Middle domain of eukaryotic initiation factor 4G (eIF4G). Also occurs in NMD2p and CBP80. The domain is rich in alpha-helices and may contain multiple alpha-helical repeats. In eIF4G, this domain binds eIF4A, eIF3, RNA and DNA [1].

Literature references

Ponting CP; , Trends Biochem Sci 2000;25:423-426.: Novel eIF4G domain homologues linking mRNA translation with nonsense-mediated mRNA decay. PUBMED:10973054

InterPro entry IPR003890

This entry represents an MIF4G-like domain. MIF4G domains share a common structure but can differ in sequence. This entry is designated "type 3", and is found in nuclear cap-binding proteins, eIF4G, and UPF2.

The MIF4G domain is a structural motif with an ARM (Armadillo) repeat-type fold, consisting of a 2-layer alpha/alpha right-handed superhelix. Proteins usually contain two or more structurally similar MIF4G domains connected by unstructured linkers. 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 PUBMED: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 PUBMED: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 PUBMED: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 PUBMED: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 PUBMED:16043493. UPF2 contains MIF4G domains, while UPF3 contains an RNP domain PUBMED:15004547.

Clan

This family is a member of clan TPR (CL0020), which contains the following 67 members:

Adaptin_N Arm Avirulence BTAD ChAPs CLASP_N Clathrin Clathrin-link Clathrin_propel Coatomer_E Cohesin_load CRM1_C Cse1 DNA_alkylation Drf_FH3 Drf_GBD DUF2225 DUF634 DUF654 FAT GUN4 HAT HEAT HEAT_PBS HemY_N IBB IBN_N IFRD IML2 KAP Leuk-A4-hydro_C LRV LRV_FeS MA3 MIF4G MIF4G_like MIF4G_like_2 Mo25 Neurochondrin NSF Paf67 ParcG PC_rep PHAT PI3Ka PPR Proteasom_PSMB PUF Rapsyn_N RPN7 Sel1 SHNi-TPR SPO22 ST7 Suf SusD TOM20_plant TPR_1 TPR_2 TPR_3 TPR_4 Upf2 V-ATPase_H_C V-ATPase_H_N Vps39_1 W2 Xpo1

Gene Ontology

Molecular function	protein binding (GO:0005515)
Biological process	RNA metabolic process (GO:0016070)

External database links

PANDIT:	PF02854
SCOP:	1h6k
SMART:	MIF4G
SYSTERS:	MIF4G

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Alignments

There are various ways to view or download the sequence alignments that we store. You can use a sequence viewer to look at either the seed or full alignment for the family, or you can look at a plain text version of the sequence in a variety of different formats. More...

View options

Alignment:	Seed (41) Full (1059) NCBI (1361) Metagenomics (51)
Viewer:

Formatting options

Alignment:	Seed (41) Full (1059)
Format:
Order:	Tree Alphabetical
Sequence:	Inserts lower case All upper case
Gaps:
Download/view:	Download View

Download options

Very large alignments can often cause problems for the formatting tool above. If you find that downloading or viewing a large alignment is problematic, you can also download a gzip-compressed, Stockholm-format file containing the seed or full alignment for this family.

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

The main seed and full alignments are generated using sequences from the UniProt sequence database. However, we also generate alignments using sequences from the NCBI sequence database and the "metaseq" metagenomics dataset.

You can view alignments from these two additional datasets using the form above, or you can download alignments of NCBI or metagenomics sequences, as gzip-compressed files.

Pfam alignments:	Seed (41) Full (1059) NCBI (1361) Metagenomics (51)
Full length sequences	Full-sequences (1059)

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER2.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed or full alignments.

Note: You can also download the data files for the seed, full, NCBI or metagenomics trees.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation

Seed source:

Alignment kindly provided by SMART

Previous IDs:

none

Type:

Family

Author:

SMART

Number in seed:

41

Number in full:

1059

Average length of the domain:

206.30 aa

Average identity of full alignment:

16 %

Average coverage of the sequence by the domain:

21.48 %

HMM information

HMM build commands:

build method: hmmbuild -o /dev/null HMM SEED

search method: hmmsearch -Z 9421015 -E 1000 HMM pfamseq

Model details:

Parameter	Sequence	Domain
Gathering cut-off	21.0	21.0
Trusted cut-off	21.7	21.0
Noise cut-off	20.7	20.8

Model length:

209

Family (HMM) version:

12

Download:

download the raw HMM for this family

Species distribution

Tree controls

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The tree shows the occurrence of this domain across different species. More...

Species trees

We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.

Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.

If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.

Interactive tree

For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.

We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.

Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.

We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.

You can use the tree controls to manipulate how the interactive tree is displayed:

show/hide the summary boxes
highlight species that are represented in the seed alignment
expand/collapse the tree or expand it to a given depth
select a sub-tree or a set of species within the tree and view them graphically or as an alignment
save a plain text representation of the tree

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Interactions

There are 3 interactions for this family. More...

MIF4G_like MIF4G MIF4G_like_2

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the MSD group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the MIF4G domain has been found.

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Family: MIF4G (PF02854)

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