EIF1AX

EIF1AX
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1D7Q, 3ZJY, 4KZY, 4KZZ
Identifiers
Aliases	EIF1AX , EIF1A, EIF1AP1, EIF4C, eIF-1A, eIF-4C, eukaryotic translation initiation factor 1A, X-linked, eukaryotic translation initiation factor 1A X-linked
External IDs	OMIM: 300186; MGI: 95298; HomoloGene: 20364; GeneCards: EIF1AX; OMA:EIF1AX - orthologs
Gene location (Human) Chr. X chromosome (human) [1] Band Xp22.12 Start 20,124,525 bp [1] End 20,141,838 bp [1]
Gene location (Mouse) Chr. Chromosome 18 (mouse) [2] Band 18|18 C Start 46,730,768 bp [2] End 46,749,523 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in endothelial cell Skeletal muscle tissue of rectus abdominis gonad lateral nuclear group of thalamus biceps brachii pons ganglionic eminence pericardium Skeletal muscle tissue of biceps brachii postcentral gyrus Top expressed in seminal vesicula otic placode saccule pineal gland otic vesicle decidua corneal stroma epiblast tail of embryo calvaria More reference expression data BioGPS More reference expression data
Gene ontology Molecular function translation factor activity, RNA binding protein binding translation initiation factor activity RNA binding Cellular component cytosol Biological process translational initiation protein biosynthesis Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1964 13664 Ensembl ENSG00000173674 ENSMUSG00000057561 UniProt P47813 Q60872 RefSeq (mRNA) NM_001412 NM_010120 NM_001374654 RefSeq (protein) NP_001403 NP_034250 Location (UCSC) Chr X: 20.12 – 20.14 Mb Chr 18: 46.73 – 46.75 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Eukaryotic translation initiation factor 1A, X-chromosomal (eIF1A) is a protein that in humans is encoded by the EIF1AX gene. ^{[5] [6] [7]} This gene encodes an essential eukaryotic translation initiation factor. The protein is a component of the 43S pre-initiation complex (PIC), which mediates the recruitment of the small 40S ribosomal subunit to the 5' cap of messenger RNAs. ^[7]

Function

See also: Eukaryotic_translation § Cap-dependent_initiation

eIF1A is an important part of the translation intiation mechanism. It is located at the A-site of the small ribosomal subunit. During translation initiation, the 43S pre-initiation complex scans along the mRNA in search of a start codon. eIF1A's N-terminal tail interacts with the initiator tRNA and the start codon by extending into the P-site, thereby increasing the fidelity of start codon selection. ^[8] After the start codon has been selected and eIF1, eIF2, and eIF5 have left the pre-initiation complex, eIF5B is recruited to continue the initiation process. Here, eIF1A interacts with eIF5B such that eIF5B is remodeled into a conformation that allows joining of the large ribosomal subunit. ^[9] After the joining of the subunit, it is the dissociation of eIF1A that permits eIF5B to rearrange again, placing the tRNA in its final position. ^[9]

Clinical significance

Mutations in this gene have been recurrently seen associated to cases of uveal melanoma with disomy 3. ^[10] eIF1A is mutated in thyroid cancers. ^[11]

Interactions

EIF1AX has been shown to interact with IPO13. ^[12]

See also

• Eukaryotic initiation factors

References

1. GRCh38: Ensembl release 89: ENSG00000173674 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000057561 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Dever TE, Wei CL, Benkowski LA, Browning K, Merrick WC, Hershey JW (Feb 1994). "Determination of the amino acid sequence of rabbit, human, and wheat germ protein synthesis factor eIF-4C by cloning and chemical sequencing". The Journal of Biological Chemistry. 269 (5): 3212–3218. doi: 10.1016/S0021-9258(17)41850-3 . PMID   8106356.
6. Lahn BT, Page DC (Oct 1997). "Functional coherence of the human Y chromosome". Science. 278 (5338). New York, N.Y.: 675–680. Bibcode:1997Sci...278..675L. doi:10.1126/science.278.5338.675. PMID   9381176.
7. "Entrez Gene: EIF1AX eukaryotic translation initiation factor 1A, X-linked".
8. Hussain T, Llácer JL, Fernández IS, Munoz A, Martin-Marcos P, Savva CG, et al. (2014). "Structural Changes Enable Start Codon Recognition by the Eukaryotic Translation Initiation Complex". Cell. 159 (3): 597–607. doi:10.1016/j.cell.2014.10.001. PMC   4217140 . PMID   25417110.
9. Lapointe CP, Grosely R, Sokabe M, Alvarado C, Wang J, Montabana E, et al. (2022). "EIF5B and eIF1A reorient initiator tRNA to allow ribosomal subunit joining". Nature. 607 (7917): 185–190. Bibcode:2022Natur.607..185L. doi:10.1038/s41586-022-04858-z. PMC   9728550 . PMID   35732735.
10. Martin M, Maßhöfer L, Temming P, Rahmann S, Metz C, Bornfeld N, et al. (Aug 2013). "Exome sequencing identifies recurrent somatic mutations in EIF1AX and SF3B1 in uveal melanoma with disomy 3". Nature Genetics. 45 (8): 933–936. doi:10.1038/ng.2674. PMC   4307600 . PMID   23793026.
11. Xu Y, Ruggero D (2020-03-09). "The Role of Translation Control in Tumorigenesis and Its Therapeutic Implications". Annual Review of Cancer Biology. 4 (1): 437–457. doi: 10.1146/annurev-cancerbio-030419-033420 . ISSN   2472-3428.
12. Mingot JM, Kostka S, Kraft R, Hartmann E, Görlich D (Jul 2001). "Importin 13: a novel mediator of nuclear import and export". The EMBO Journal. 20 (14): 3685–3694. doi:10.1093/emboj/20.14.3685. PMC   125545 . PMID   11447110.

Further reading

• Battiste JL, Pestova TV, Hellen CU, Wagner G (Jan 2000). "The eIF1A solution structure reveals a large RNA-binding surface important for scanning function". Molecular Cell. 5 (1): 109–119. doi: 10.1016/S1097-2765(00)80407-4 . PMID   10678173.
• Choi SK, Olsen DS, Roll-Mecak A, Martung A, Remo KL, Burley SK, et al. (Oct 2000). "Physical and functional interaction between the eukaryotic orthologs of prokaryotic translation initiation factors IF1 and IF2". Molecular and Cellular Biology. 20 (19): 7183–7191. doi:10.1128/MCB.20.19.7183-7191.2000. PMC   86272 . PMID   10982835.
• Mingot JM, Kostka S, Kraft R, Hartmann E, Görlich D (Jul 2001). "Importin 13: a novel mediator of nuclear import and export". The EMBO Journal. 20 (14): 3685–3694. doi:10.1093/emboj/20.14.3685. PMC   125545 . PMID   11447110.
• Sørensen HP, Hedegaard J, Sperling-Petersen HU, Mortensen KK (May 2001). "Remarkable conservation of translation initiation factors: IF1/eIF1A and IF2/eIF5B are universally distributed phylogenetic markers". IUBMB Life. 51 (5): 321–327. doi:10.1080/152165401317190842. PMID   11699879. S2CID   45654480.
• Bohnsack MT, Regener K, Schwappach B, Saffrich R, Paraskeva E, Hartmann E, et al. (Nov 2002). "Exp5 exports eEF1A via tRNA from nuclei and synergizes with other transport pathways to confine translation to the cytoplasm". The EMBO Journal. 21 (22): 6205–6215. doi:10.1093/emboj/cdf613. PMC   137205 . PMID   12426392.
• Olsen DS, Savner EM, Mathew A, Zhang F, Krishnamoorthy T, Phan L, et al. (Jan 2003). "Domains of eIF1A that mediate binding to eIF2, eIF3 and eIF5B and promote ternary complex recruitment in vivo". The EMBO Journal. 22 (2): 193–204. doi:10.1093/emboj/cdg030. PMC   140105 . PMID   12514125.
• Marintchev A, Kolupaeva VG, Pestova TV, Wagner G (Feb 2003). "Mapping the binding interface between human eukaryotic initiation factors 1A and 5B: a new interaction between old partners". Proceedings of the National Academy of Sciences of the United States of America. 100 (4): 1535–1540. Bibcode:2003PNAS..100.1535M. doi: 10.1073/pnas.0437845100 . PMC   149867 . PMID   12569173.
• Agate RJ, Choe M, Arnold AP (Feb 2004). "Sex differences in structure and expression of the sex chromosome genes CHD1Z and CHD1W in zebra finches". Molecular Biology and Evolution. 21 (2): 384–396. doi: 10.1093/molbev/msh027 . PMID   14660691.
• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, et al. (Oct 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–1178. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID   16189514. S2CID   4427026.
• Kim S, Kim GJ, Miyoshi H, Moon SH, Ahn SE, Lee JH, et al. (Aug 2007). "Efficiency of the elongation factor-1alpha promoter in mammalian embryonic stem cells using lentiviral gene delivery systems". Stem Cells and Development. 16 (4): 537–545. doi:10.1089/scd.2006.0088. PMID   17784828.

External links

• Overview of all the structural information available in the PDB for UniProt : P47813 (Eukaryotic translation initiation factor 1A, X-chromosoma) at the PDBe-KB .