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EUKARYOTIC TRANSLATION INITIATION FACTOR 2D; EIF2D

EUKARYOTIC TRANSLATION INITIATION FACTOR 2D; EIF2D

Alternative titles; symbolsHEPATOCELLULAR CARCINOMA-ASSOCIATED ANTIGEN 56; HCA56LIGATIN, FORMERLY; LGTN, FORMERLYHGNC Approved Gene Symbol: EIF2DCytogenetic loca...

Alternative titles; symbols

  • HEPATOCELLULAR CARCINOMA-ASSOCIATED ANTIGEN 56; HCA56
  • LIGATIN, FORMERLY; LGTN, FORMERLY

HGNC Approved Gene Symbol: EIF2D

Cytogenetic location: 1q32.1 Genomic coordinates (GRCh38): 1:206,572,483-206,612,465 (from NCBI)

▼ 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 and Expression
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 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.

Tags: 1q32.1