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14  structures 1032  species 1  interaction 3699  sequences 84  architectures

Family: W2 (PF02020)

Summary: eIF4-gamma/eIF5/eIF2-epsilon

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This is the Wikipedia entry entitled "EIF-W2 protein domain". More...

EIF-W2 protein domain Edit Wikipedia article

W2
PDB 1paq EBI.jpg
crystal structure of the catalytic fragment of eukaryotic initiation factor 2b epsilon
Identifiers
Symbol W2
Pfam PF02020
Pfam clan CL0020
InterPro IPR003307
SCOP 1paq
SUPERFAMILY 1paq

In molecular biology, the protein domain eIF4-gamma/eIF5/eIF2-epsilon is a family of evolutionarily related proteins. This domain is found at the C-terminus of several translation Initiation factors.[1] It was first detected at the very C-termini of the yeast protein GCD6, eIF-2B epsilon, and two other eukaryotic translation initiation factors, eIF-4 gamma and eIF-5 and it may be involved in the interaction of eIF-2B, eIF-4 gamma, and eIF-5 with eIF-2.[1]

Function

In molecular biology, the eIF-W2 domain functions as the binding site for Mnk eIF4E kinase,[2] an enzyme that phosphorylates eukaryotic initiation factor 4E (eIF4E). For eIF2B-epsilon, the W2 C-terminal domain functions in guanine nucleotide exchange on eIF2. For eIF5, the W2 domain functions in mediating the multifactor complex (MFC) formation with eIF1, eIF2-GTP, eIF3 and Met-tRNAiMet. The eIF5 W2 C-terminal domain and the adjacent N-terminal linker region is responsible for the GDI activity against eIF2-GDP.[3]

Domain Structure

The W2 domain has a globular fold and is exclusively composed out of alpha-helices.[4][5][6] The structure can be divided into a structural C-terminal core onto which the two N-terminal helices are attached. The core contains two aromatic/acidic residue-rich regions (AA boxes), which are important for mediating protein-protein interactions.

This entry covers the entire W2 domain, which is part of the TPR clan.

Translation

Translation initiation is a well regulated and highly coordinated cellular process in eukaryotes, in which at least 11 eukaryotic initiation factors (eIFs) are included.[7] These factors come together to form the pre-initiation complex.

Eukaryotic initiation factors

The W2 domain (two invariant tryptophans) is a region of approximately 165 amino acids which is found in the C-terminus of the following eukaryotic initiation factors(eIFs):

Examples

Genes encoding proteins containing this domain include AAG1, BZW1, BZW2, EIF2B5, EIF4G1, EIF4G2, EIF4G3, and EIF5.

References

  1. ^ a b Koonin EV (1995). "Multidomain organization of eukaryotic guanine nucleotide exchange translation initiation factor eIF-2B subunits revealed by analysis of conserved sequence motifs". Protein Sci. 4 (8): 1608–1617. doi:10.1002/pro.5560040819. PMC 2143190Freely accessible. PMID 8520487. 
  2. ^ Singh CR, Watanabe R, Zhou D, Jennings MD, Fukao A, Lee B, et al. (2011). "Mechanisms of translational regulation by a human eIF5-mimic protein". Nucleic Acids Res. 39 (19): 8314–28. doi:10.1093/nar/gkr339. PMC 3201852Freely accessible. PMID 21745818. 
  3. ^ Fukunaga R, Hunter T (1997). "MNK1, a new MAP kinase-activated protein kinase, isolated by a novel expression screening method for identifying protein kinase substrates". EMBO J. 16 (8): 1921–33. doi:10.1093/emboj/16.8.1921. PMC 1169795Freely accessible. PMID 9155018. 
  4. ^ Boesen T, Mohammad SS, Pavitt GD, Andersen GR (March 2004). "Structure of the catalytic fragment of translation initiation factor 2B and identification of a critically important catalytic residue". J. Biol. Chem. 279 (11): 10584–92. doi:10.1074/jbc.M311055200. PMID 14681227. 
  5. ^ Wei Z, Xue Y, Xu H, Gong W (May 2006). "Crystal structure of the C-terminal domain of S.cerevisiae eIF5". J. Mol. Biol. 359 (1): 1–9. doi:10.1016/j.jmb.2006.03.037. PMID 16616930. 
  6. ^ Bieniossek C, Schütz P, Bumann M, Limacher A, Uson I, Baumann U (July 2006). "The crystal structure of the carboxy-terminal domain of human translation initiation factor eIF5". J. Mol. Biol. 360 (2): 457–65. doi:10.1016/j.jmb.2006.05.021. PMID 16781736. 
  7. ^ Koonin EV (August 1995). "Multidomain organization of eukaryotic guanine nucleotide exchange translation initiation factor eIF-2B subunits revealed by analysis of conserved sequence motifs". Protein Sci. 4 (8): 1608–17. doi:10.1002/pro.5560040819. PMC 2143190Freely accessible. PMID 8520487. 

This article incorporates text from the public domain Pfam and InterPro IPR003307

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

eIF4-gamma/eIF5/eIF2-epsilon Provide feedback

This domain of unknown function is found at the C-terminus of several translation initiation factors [1].

Literature references

  1. Koonin EV; , Protein Sci 1995;4:1608-1617.: Multidomain organization of eukaryotic guanine nucleotide exchange translation initiation factor eIF-2B subunits revealed by analysis of conserved sequence motifs. PUBMED:8520487 EPMC:8520487


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR003307

Translation initiation is a sophisticated, well regulated and highly coordinated cellular process in eukaryotes, in which at least 11 eukayrotic initiation factors (eIFs) are included. The W2 domain (two invariant tryptophans) is a region of ~165 amino acids which is found in the C terminus of the following eIFs [PUBMED:8520487, PUBMED:10958635, PUBMED:14681227, PUBMED:16616930, PUBMED:16781736]:

  • Eukaryotic translation initiation factor 2B epsilon (eIF-2B-epsilon).
  • Eukaryotic translation initiation factor 4 gamma (eIF-4-gamma).
  • Eukaryotic translation initiation factor 5 (eIF-5), a GTPase-activating protein (GAP) specific for eIF2.

The W2 domain has a globular fold and is exclusively composed out of alpha- helices [PUBMED:14681227, PUBMED:16616930, PUBMED:16781736]. The structure can be divided into a structural C-terminal core onto which the two N-terminal helices are attached. The core contains two aromatic/acidic residue-rich regions (AA boxes), which are important for mediating protein-protein interactions.

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

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

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Pfam Clan

This family is a member of clan TPR (CL0020), which has the following description:

Tetratricopeptide-like repeats are found in a numerous and diverse proteins involved in such functions as cell cycle regulation, transcriptional control, mitochondrial and peroxisomal protein transport, neurogenesis and protein folding.

The clan contains the following 149 members:

Adaptin_N Alkyl_sulf_dimr ANAPC3 ANAPC5 ANAPC8 API5 Arm Arm_2 Arm_3 Atx10homo_assoc B56 BAF250_C BTAD CAS_CSE1 ChAPs CHIP_TPR_N CLASP_N Clathrin Clathrin-link Clathrin_H_link Clathrin_propel Cnd1 Cnd3 Coatomer_E Cohesin_HEAT Cohesin_load ComR_TPR COPI_C CPL CRM1_C Cse1 DHR-2 DNA_alkylation Drf_FH3 Drf_GBD DUF1822 DUF2019 DUF2225 DUF3385 DUF3458_C DUF3808 DUF3856 DUF4042 DUF924 EST1 EST1_DNA_bind FAT Fis1_TPR_C Fis1_TPR_N Foie-gras_1 GUN4_N HAT HEAT HEAT_2 HEAT_EZ HEAT_PBS HemY_N HrpB1_HrpK IBB IBN_N IFRD KAP Leuk-A4-hydro_C LRV LRV_FeS MA3 MIF4G MIF4G_like MIF4G_like_2 MMS19_C Mo25 MRP-S27 NARP1 Neurochondrin Nipped-B_C Nro1 NSF Paf67 ParcG PC_rep PHAT PI3Ka PknG_TPR PPP5 PPR PPR_1 PPR_2 PPR_3 PPR_long PPTA Proteasom_PSMB PUF Rab5-bind Rapsyn_N RIX1 RPM2 RPN7 Sel1 SHNi-TPR SNAP SPO22 SRP_TPR_like ST7 Suf SusD-like SusD-like_2 SusD-like_3 SusD_RagB SYCP2_ARLD TAF6_C TAL_effector TAtT Tcf25 TIP120 TOM20_plant TPR_1 TPR_10 TPR_11 TPR_12 TPR_14 TPR_15 TPR_16 TPR_17 TPR_18 TPR_19 TPR_2 TPR_20 TPR_21 TPR_3 TPR_4 TPR_5 TPR_6 TPR_7 TPR_8 TPR_9 TPR_MalT UNC45-central Upf2 V-ATPase_H_C V-ATPase_H_N Vac14_Fab1_bd Vitellogenin_N Vps39_1 W2 Wzy_C_2 Xpo1 YcaO_C YfiO Zmiz1_N

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(394)
Full
(3699)
Representative proteomes UniProt
(5787)
NCBI
(9124)
Meta
(4)
RP15
(931)
RP35
(1915)
RP55
(2845)
RP75
(3408)
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PP/heatmap 1 View               

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(394)
Full
(3699)
Representative proteomes UniProt
(5787)
NCBI
(9124)
Meta
(4)
RP15
(931)
RP35
(1915)
RP55
(2845)
RP75
(3408)
Alignment:
Format:
Order:
Sequence:
Gaps:
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(394)
Full
(3699)
Representative proteomes UniProt
(5787)
NCBI
(9124)
Meta
(4)
RP15
(931)
RP35
(1915)
RP55
(2845)
RP75
(3408)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download   Download  

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

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's seed alignment. 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 alignment.

Note: You can also download the data file for the tree.

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 View help on the curation process

Seed source: [1]
Previous IDs: IF5_eIF4_eIF2;
Type: Family
Sequence Ontology: SO:0100021
Author: Bateman A
Number in seed: 394
Number in full: 3699
Average length of the domain: 80.80 aa
Average identity of full alignment: 27 %
Average coverage of the sequence by the domain: 11.84 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 30.0 30.0
Trusted cut-off 30.0 30.0
Noise cut-off 29.9 29.8
Model length: 79
Family (HMM) version: 18
Download: download the raw HMM for this family

Species distribution

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Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence

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Interactions

There is 1 interaction for this family. More...

W2

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 PDBe 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 W2 domain has been found. There are 14 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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