Eukaryotic translation initiation factor 2D (EIF2D)

The protein contains 584 amino acids for an estimated molecular weight of 64706 Da.

 

Translation initiation factor that is able to deliver tRNA to the P-site of the eukaryotic ribosome in a GTP-independent manner. The binding of Met-tRNA(I) occurs after the AUG codon finds its position in the P-site of 40S ribosomes, the situation that takes place during initiation complex formation on some specific RNAs. Its activity in tRNA binding with 40S subunits does not require the presence of the aminoacyl moiety. Possesses the unique ability to deliver non-Met (elongator) tRNAs into the P-site of the 40S subunit. In addition to its role in initiation, can promote release of deacylated tRNA and mRNA from recycled 40S subunits following ABCE1-mediated dissociation of post-termination ribosomal complexes into subunits. (updated: Feb. 4, 2015)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  3. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

Interpro domains
Total structural coverage: 57%
Model score: 0
No model available.

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VariantDescription
dbSNP:rs35252702

The reference OMIM entry for this protein is 613709

Eukaryotic translation initiation factor 2d; eif2d
Hepatocellular carcinoma-associated antigen 56; hca56
Ligatin, formerly; lgtn, formerly

DESCRIPTION

EIF2D is a translation initiation factor that delivers tRNA to the P site of the 40S ribosome in a GTP-independent manner. Previously, EIF2D was erroneously called ligatin (LGTN; 151625) in the literature (see

NOMENCLATURE

) (Dmitriev et al., 2010).

CLONING

Using mass spectrometry, Dmitriev et al. (2010) identified EIF2D as a factor purified from HeLa cells that promoted GTP-independent binding of the initiator tRNA, or met-tRNA-i(met) (see 180621), to the P site of the 40S ribosome. By RT-PCR of HEK293T cell total RNA, Dmitriev et al. (2010) isolated the EIF2D cDNA. The deduced 584-amino acid EIF2D protein has a calculated molecular mass of 65 kD. It contains an N-terminal PUA domain, which is found in proteins involved in RNA metabolism, and a C-terminal SUI1 domain, which is found in EIF1 and plays a role in initiator codon recognition. EIF2D purified from HeLa cells had an apparent molecular mass of 70 to 72 kD. Transfected EIF2D colocalized with endogenous EIF3 (see 602039) in the cytoplasm of HeLa cells. EIF2D orthologs are present in all eukaryotic genomes.

GENE FUNCTION

Dmitriev et al. (2010) showed that recombinant human EIF2D promoted binding of met-tRNA-i(met) to the P site of the 40S ribosome in a GTP-independent manner. EIF2D could not deliver met-tRNA-i(met) to the 40S ribosome in the absence of the AUG codon. The aminoacyl moiety of met-tRNA-i(met) was dispensable for EIF2D-promoted formation of its complex with the 40S ribosome. In addition, EIF2D was not strictly specific for the initiator tRNA and AUG codon and could deliver some elongator tRNAs (e.g., tRNA(phe)) to the P site of the 40S ribosome when it was programmed with the corresponding codon. EIF2D stabilized the complex of 40S ribosomes with leaderless mRNA, and it strongly promoted formation of complexes of 40S ribosomes with RNAs containing single-stranded A-rich 5-prime UTRs.

MAPPING

Gross (2011) mapped the EIF2D gene to chromosome 1q32.1 based on an alignment of the EIF2D sequence (GenBank GENBANK AF220417) with the genomic sequence (GRCh37). Using FISH, Malnar-Dragojevic et al. (1997) mapped the mouse Eif2d gene, which they called ligatin (see

NOMENCLATURE

), to chromosome 1F. This region is syntenic with human chromosome 1q31-q32.

NOMENCLATURE

Dmitriev et al. (2010) noted that a partial human EIF2D sequence containing a frameshift had previously been characterized as a cDNA for ligatin (LGTN; 151625) by Jakoi et al. (1989). Dmitriev et al. (2010) presented several lines of evidence showing that EIF2D is unrelated to ligatin, a peripheral membrane protein that binds and localizes phosphoglycoproteins at the cell surface. Dmitriev et al. (2010) pointed out that the misidentification of EIF2D as ligatin resulted in several reports, including those of Jakoi et al. (1995), Severt et al. (1999), Dang et al. (2006), and Lee et al. (2007), in which expression and/or regulation of EIF2D were erroneously attributed to ligatin. ... More on the omim web site

Subscribe to this protein entry history

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 613709 was added.