UBA5

Chr 3q22.1

ubiquitin like modifier activating enzyme 5

Aliases:: FLJ23251
MANE:: ENST00000356232.10

OMIM: 610552 ↗NCBI: 79876 ↗Ensembl ↗

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Predicted protein structure

AlphaFold predicted structure

UBA5 · Q9GZZ9

v62025-08-01

Predicted Aligned Error matrix for UBA5 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

86.8/ 100

Confident

404 residues

Confidence breakdown

Very high(≥ 90)67%
Confident(70–90)15%
Low(50–70)13%
Very low(< 50)5%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

DDG2P
BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy
BIALLELIC, autosomal or pseudoautosomal
Hereditary ataxia with onset in adulthood
BIALLELIC, autosomal or pseudoautosomal
Intellectual disability
BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly
BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies
BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder
BIALLELIC, autosomal or pseudoautosomal

Disease associations (Open Targets)

developmental and epileptic encephalopathy, 44
0.79
spinocerebellar ataxia, autosomal recessive 24
0.69
Childhood-onset autosomal recessive slowly progressive spinocerebellar ataxia
0.60
neurodegenerative disease
0.53
Intellectual disability
0.52
hereditary disease
0.45
developmental and epileptic encephalopathy
0.43
genetic developmental and epileptic encephalopathy
0.37
undetermined early-onset epileptic encephalopathy
0.37
dengue disease
0.37

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Ubiquitin-like modifier-activating enzyme 5

E1-like enzyme which specifically catalyzes the first step in ufmylation (PubMed:15071506, PubMed:18442052, PubMed:20368332, PubMed:25219498, PubMed:26929408, PubMed:27545674, PubMed:27545681, PubMed:27653677, PubMed:30412706, PubMed:30626644, PubMed:34588452). Activates UFM1 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 UFM1-E1 thioester and free AMP (PubMed:20368332, PubMed:26929408, PubMed:27653677, PubMed:30412706). Activates UFM1 via a trans-binding mechanism, in which UFM1 interacts with distinct sites in both subunits of the UBA5 homodimer (PubMed:27653677). Trans-binding also promotes stabilization of the UBA5 homodimer, and enhances ATP-binding (PubMed:29295865). Transfer of UFM1 from UBA5 to the E2-like enzyme UFC1 also takes place using a trans mechanism (PubMed:27653677, PubMed:34588452). Ufmylation plays a key role in various processes, such as ribosome recycling, response to DNA damage, interferon response or reticulophagy (also called ER-phagy) (PubMed:30412706, PubMed:32160526, PubMed:35394863). Ufmylation is essential for erythroid differentiation of both megakaryocytes and erythrocytes (By similarity)