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UBA1 gene

ubiquitin like modifier activating enzyme 1
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Normal Function

The UBA1 gene provides instructions for making the ubiquitin-activating enzyme E1. This enzyme is necessary for the ubiquitin-proteasome system, which targets damaged or unneeded proteins to be broken down (degraded) within cells. Protein degradation helps to maintain the proper balance of protein production and breakdown (protein homeostasis). Old proteins need to be removed to make way for new proteins to allow cells to function and survive. The ubiquitin-proteasome system acts as the cell's quality control system by disposing of damaged, misshapen, and excess proteins.

Ubiquitin-activating enzyme E1 is responsible for the first step in the ubiquitin-proteasome system; it turns on (activates) a small protein called ubiquitin. With the assistance of other proteins, the active ubiquitin attaches to a protein that is to be broken down. When a chain of ubiquitin proteins is attached to a protein, the protein is recognized and destroyed by a complex of enzymes called a proteasome.

Health Conditions Related to Genetic Changes

X-linked infantile spinal muscular atrophy

At least four mutations in the UBA1 gene have been found to cause X-linked infantile spinal muscular atrophy. This condition is characterized by severe muscle weakness that begins at birth or in early infancy and affects only boys. Weakness in the chest muscles that control breathing often causes death from respiratory failure in early childhood.

Each of the UBA1 gene mutations that causes X-linked infantile spinal muscular atrophy changes one DNA building block (nucleotide) in an area of the gene known as exon 15. These mutations reduce the activity, function, or production of the enzyme. This shortage of functional enzyme allows damaged or unneeded proteins to build up inside cells instead of being degraded, which may damage cells and contribute to cell death. This buildup also disrupts protein homeostasis. If damaged or unneeded proteins are not degraded, they can impair normal cell functions by stopping the production of new proteins. An imbalance in protein production and breakdown can ultimately lead to cell death. Specialized nerve cells that control muscle movement (motor neurons) are particularly susceptible to disruptions in cell function, likely due to their large size. Loss of these cells causes many of the signs and symptoms of X-linked infantile spinal muscular atrophy.

More About This Health Condition

Other Names for This Gene

  • A1S9
  • A1S9T
  • A1ST
  • AMCX1
  • CFAP124
  • GXP1
  • MGC4781
  • SMAX2
  • UBA1, ubiquitin-activating enzyme E1 homolog A
  • UBA1_HUMAN
  • UBA1A
  • UBE1
  • UBE1X
  • ubiquitin-activating enzyme E1
  • ubiquitin-like modifier activating enzyme 1

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Research Resources

References

  • Balak CD, Hunter JM, Ahearn ME, Wiley D, D'urso G, Baumbach-Reardon L. Functional characterizations of rare UBA1 variants in X-linked Spinal Muscular Atrophy. F1000Res. 2017 Sep 4;6:1636. doi: 10.12688/f1000research.11878.1. eCollection 2017. Citation on PubMed or Free article on PubMed Central
  • Groen EJN, Gillingwater TH. UBA1: At the Crossroads of Ubiquitin Homeostasis and Neurodegeneration. Trends Mol Med. 2015 Oct;21(10):622-632. doi: 10.1016/j.molmed.2015.08.003. Review. Citation on PubMed or Free article on PubMed Central
  • Ramser J, Ahearn ME, Lenski C, Yariz KO, Hellebrand H, von Rhein M, Clark RD, Schmutzler RK, Lichtner P, Hoffman EP, Meindl A, Baumbach-Reardon L. Rare missense and synonymous variants in UBE1 are associated with X-linked infantile spinal muscular atrophy. Am J Hum Genet. 2008 Jan;82(1):188-93. doi: 10.1016/j.ajhg.2007.09.009. Citation on PubMed or Free article on PubMed Central
  • Schulman BA, Harper JW. Ubiquitin-like protein activation by E1 enzymes: the apex for downstream signalling pathways. Nat Rev Mol Cell Biol. 2009 May;10(5):319-31. doi: 10.1038/nrm2673. Epub 2009 Apr 8. Review. Citation on PubMed or Free article on PubMed Central
  • Zheng M, Liu J, Yang Z, Gu X, Li F, Lou T, Ji C, Mao Y. Expression, purification and characterization of human ubiquitin-activating enzyme, UBE1. Mol Biol Rep. 2010 Mar;37(3):1413-9. doi: 10.1007/s11033-009-9525-3. Epub 2009 Apr 3. Citation on PubMed
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