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Details on Person UniProt:P22314 UBA1

Class:IdReferenceGeneProduct:66719
_chainChangeLoginitiator methionine:1 added on Sat February 7 2015;chain:2-1058 added on Sat February 7 2015;initiator methionine: for 66719 added on Sun February 16 2020;initiator methionine:1 for 66719 removed on Fri Nov 03 2023;initiator methionine: for 66719 removed on Fri Aug 15 2025;initiator methionine: for 66719 removed on Fri Aug 15 2025;initiator methionine:1 for 66719 added on Fri Aug 15 2025;initiator methionine:1 for 66719 added on Fri Aug 15 2025
_displayNameUniProt:P22314 UBA1
_timestamp2025-08-15 21:50:08
chaininitiator methionine:1
chain:2-1058
initiator methionine:1
checksum4B413AAA75FAA562
commentFUNCTION 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).CATALYTIC ACTIVITY ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine = AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine.PATHWAY Protein modification; protein ubiquitination.SUBUNIT Monomer (By similarity). Interacts with GAN (via BTB domain).INTERACTION Detected in erythrocytes (at protein level). Ubiquitous.DOMAIN The first 11 amino acids are essential for phosphorylation and exclusive nuclear localization.PTM ISGylated.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE 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).MISCELLANEOUS There are two active sites within the E1 molecule, allowing it to accommodate two ubiquitin moieties at a time, with a new ubiquitin forming an adenylate intermediate as the previous one is transferred to the thiol site.SIMILARITY Belongs to the ubiquitin-activating E1 family.
descriptionrecommendedName: Ubiquitin-like modifier-activating enzyme 1 ecNumber evidence="19"6.2.1.45 alternativeName: Protein A1S9 alternativeName: Ubiquitin-activating enzyme E1
geneNameUBA1
A1S9T
UBE1
identifierP22314
isSequenceChangedFALSE
keyword3D-structure
Acetylation
Alternative initiation
ATP-binding
Cytoplasm
Direct protein sequencing
Disease variant
Ligase
Mitochondrion
Neurodegeneration
Nucleotide-binding
Nucleus
Phosphoprotein
Proteomics identification
Reference proteome
Repeat
Ubl conjugation
Ubl conjugation pathway
modified[InstanceEdit:9836292] Weiser, Joel, 2023-05-25
[InstanceEdit:9852000] Weiser, Joel, 2023-11-03
[InstanceEdit:9917590] Weiser, Joel, 2024-08-09
[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
[InstanceEdit:9963647] Weiser, Joel, 2025-08-15
nameUBA1
referenceDatabase[ReferenceDatabase:2] UniProt
referenceGene[ReferenceDNASequence:8958633] ENSEMBL:ENSG00000130985 UBA1 [Homo sapiens]
secondaryIdentifierUBA1_HUMAN
Q5JRR8
Q96E13
sequenceLength1058
species[Species:48887] Homo sapiens
(isoformParent)[ReferenceIsoform:8976316] UniProt:P22314-1 UBA1 [Homo sapiens]
[ReferenceIsoform:8976317] UniProt:P22314-2 UBA1 [Homo sapiens]
(referenceEntity)[EntityWithAccessionedSequence:947698] UBA1 [cytosol] [Homo sapiens]
[EntityWithAccessionedSequence:8852116] UBA1 [nucleoplasm] [Homo sapiens]
[EntityWithAccessionedSequence:8957945] UBA1 [extracellular region] [Homo sapiens]
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No pathways have been reviewed or authored by UniProt:P22314 UBA1 (66719)