E1 Ubiquitin Activating Enzyme 1/UBA1

The first 11 amino acids are essential for phosphorylation and exclusive nuclear localization.

Catalyzes the first step in ubiquitin conjugation to mark cellular proteins for degradation through the ubiquitin-proteasome system (PubMed:1447181, PubMed:1606621, PubMed:33108101). Activates ubiquitin by first adenylating its C-terminal glycine residue with ATP, and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding a ubiquitin-E1 thioester and free AMP (PubMed:1447181). Essential for the formation of radiation-induced foci, timely DNA repair and for response to replication stress. Promotes the recruitment of TP53BP1 and BRCA1 at DNA damage sites (PubMed:22456334).

Spinal muscular atrophy X-linked 2

SMAX2

A lethal infantile form of spinal muscular atrophy, a neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. Clinical features include hypotonia, areflexia, and multiple congenital contractures.

None

The disease is caused by variants affecting the gene represented in this entry.

VEXAS syndrome

VEXAS

A sporadic, often fatal, treatment-refractory inflammatory syndrome that develops in late adulthood. Clinical features include fevers, cytopenias, characteristic vacuoles in myeloid and erythroid precursor cells, dysplastic bone marrow, neutrophilic cutaneous and pulmonary inflammation, chondritis, and vasculitis. The disease affects only males and is associated with de novo somatic mutations.

None

The disease is caused by variants affecting the gene represented in this entry. Somatic variants affecting the initiator methionine of isoform 2 are recurrently found in VEXAS patients. These variants cause loss of isoform 2 and production of a shorter isoform with strongly reduced enzymatic activity from a downstream methionine (Met-67).

Protein modification; protein ubiquitination.

ISGylated.

Belongs to the ubiquitin-activating E1 family.

Detected in erythrocytes (at protein level). Ubiquitous.

• Cytoplasm
• Mitochondrion
• Nucleus
• Isoform 1
• Nucleus
• Isoform 2
• Cytoplasm

A1S9T, UBE1, UBA1, Ubiquitin-like modifier-activating enzyme 1, Protein A1S9, Ubiquitin-activating enzyme E1

• entrezGene:7314
• entrezGene:7317
• omim:314370
• swissprot:P22314
• swissprot:P0CG47
• swissprot:P0CG48
• swissprot:P62979
• swissprot:P62987
• swissprot:P62988

Proteins

Neuroscience

117849Da