UBA3
NEDD8-activating enzyme E1 catalytic subunit
Also known as: hUba3, NAE2, UBA3_HUMAN, UBE1C
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q8TBC4
- Gene
- UBA3
- Ensembl
- ENSG00000144744
- Chromosome
- 3
- Canonical length
- 463 aa
- Protein class
- Enzymes, Metabolic proteins, Predicted intracellular proteins
- Subcellular location
- Nucleoplasm,Plasma membrane,Centrosome,Cytosol
OverviewNCBI Gene
The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes a member of the E1 ubiquitin-activating enzyme family. The encoded enzyme associates with AppBp1, an amyloid beta precursor protein binding protein, to form a heterodimer, and then the enzyme complex activates NEDD8, a ubiquitin-like protein, which regulates cell division, signaling and embryogenesis. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Canonical amino-acid sequenceUniProt
463 residues, UniProt reviewed canonical sequence.
>Q8TBC4|UBA3
1 MADGEEPEKK RRRIEELLAE KMAVDGGCGD TGDWEGRWNH VKKFLERSGP FTHPDFEPST
61 ESLQFLLDTC KVLVIGAGGL GCELLKNLAL SGFRQIHVID MDTIDVSNLN RQFLFRPKDI
121 GRPKAEVAAE FLNDRVPNCN VVPHFNKIQD FNDTFYRQFH IIVCGLDSII ARRWINGMLI
181 SLLNYEDGVL DPSSIVPLID GGTEGFKGNA RVILPGMTAC IECTLELYPP QVNFPMCTIA
241 SMPRLPEHCI EYVRMLQWPK EQPFGEGVPL DGDDPEHIQW IFQKSLERAS QYNIRGVTYR
301 LTQGVVKRII PAVASTNAVI AAVCATEVFK IATSAYIPLN NYLVFNDVDG LYTYTFEAER
361 KENCPACSQL PQNIQFSPSA KLQEVLDYLT NSASLQMKSP AITATLEGKN RTLYLQSVTS
421 IEERTRPNLS KTLKELGLVD GQELAVADVT TPQTVLFKLH FTSLocalizationUniProt · AlphaFold · HPA
Whether an antibody against UBA3 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.29
- Highest tissue expression
- 62 nTPM
Expression across tissuesHPA
Tissue
- heart muscle: 62 nTPM
- retina: 57 nTPM
- tonsil: 47 nTPM
- lymph node: 46 nTPM
- parathyroid gland: 43 nTPM
- skin: 43 nTPM
Single-cell type
- neutrophils: 150 nCPM
- rod photoreceptor cells: 146 nCPM
- cytotrophoblasts: 116 nCPM
- retinal pigment epithelial cells: 115 nCPM
- neutrophil progenitors: 115 nCPM
- choroid plexus epithelial cells: 110 nCPM
Immune cell
- basophil: 87 nTPM
- eosinophil: 71 nTPM
- non-classical monocyte: 57 nTPM
- intermediate monocyte: 53 nTPM
- total PBMC: 53 nTPM
- classical monocyte: 45 nTPM
Brain region
- white matter: 872 nTPM
- medulla oblongata: 606 nTPM
- basal ganglia: 571 nTPM
- hypothalamus: 503 nTPM
- pons: 502 nTPM
- thalamus: 499 nTPM
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.41
- gnomAD pLI
- 0.5
- gnomAD missense Z
- 1.17
- DepMap mean gene effect
- -0.61
- DepMap dependency class
- common
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- endomitotic cell cycle
- post-translational protein modification
- protein modification process
- protein neddylation
- proteolysis
- regulation of cell cycle
Molecular functions
- ATP binding
- identical protein binding
- NEDD8 activating enzyme activity
- NEDD8 transferase activity
- protein heterodimerization activity
Cellular components
Protein domainsUniProt · Pfam · InterPro
- THIF-type NAD/FAD binding fold
- Ubiquitin activating enzyme, alpha domain superfamily
- Ubiquitin-activating enzyme E1, Cys active site
- Ubiquitin-activating enzyme-like
- ThiF/MoeB/HesA family
- ThiF family
- E2 binding
- NEDD8-activating enzyme E1 catalytic subunit, N-terminal domain
- E2 binding domain
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of UBA3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads UBA3 as an antibody target. Whether an autoantibody or antibody against UBA3 could matter depends on whether native UBA3 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
UBA3 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label UBA3 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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