UBA5 ubiquitin like modifier activating enzyme 5 [Homo sapiens (human)] - Gene

Summary

Official Symbol: UBA5provided by HGNC
Official Full Name: ubiquitin like modifier activating enzyme 5provided by HGNC
Primary source: HGNC:HGNC:23230
See related: Ensembl:ENSG00000081307 MIM:610552; AllianceGenome:HGNC:23230
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: DEE44; EIEE44; SCAR24; THIFP1; UBE1DC1
Summary: This gene encodes a member of the E1-like ubiquitin-activating enzyme family. This protein activates ubiquitin-fold modifier 1, a ubiquitin-like post-translational modifier protein, via the formation of a high-energy thioester bond. Alternative splicing results in multiple transcript variants. A pseudogene of this gene has been identified on chromosome 1. [provided by RefSeq, Feb 2016]
Expression: Ubiquitous expression in kidney (RPKM 9.2), thyroid (RPKM 8.7) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 3q22.1

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (132654430..132679794)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (135398923..135424284)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (132373274..132398638)

Chromosome 3 - NC_000003.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Allelic strengths of encephalopathy-associated UBA5 variants correlate between in vivo and in vitro assays.
Title: Allelic strengths of encephalopathy-associated UBA5 variants correlate between in vivo and in vitro assays.
Homozygous UBA5 Variant Leads to Hypomyelination with Thalamic Involvement and Axonal Neuropathy.
Title: Homozygous UBA5 Variant Leads to Hypomyelination with Thalamic Involvement and Axonal Neuropathy.
Structure and dynamics of UBA5-UFM1 complex formation showing new insights in the UBA5 activation mechanism.
Title: Structure and dynamics of UBA5-UFM1 complex formation showing new insights in the UBA5 activation mechanism.
Structural basis for UFM1 transfer from UBA5 to UFC1.
Title: Structural basis for UFM1 transfer from UBA5 to UFC1.
A Concerted Action of UBA5 C-Terminal Unstructured Regions Is Important for Transfer of Activated UFM1 to UFC1.
Title: A Concerted Action of UBA5 C-Terminal Unstructured Regions Is Important for Transfer of Activated UFM1 to UFC1.
A homozygous UBA5 pathogenic variant causes a fatal congenital neuropathy.
Title: A homozygous UBA5 pathogenic variant causes a fatal congenital neuropathy.
An atypical LIR motif within UBA5 (ubiquitin like modifier activating enzyme 5) interacts with GABARAP proteins and mediates membrane localization of UBA5.
Title: An atypical LIR motif within UBA5 (ubiquitin like modifier activating enzyme 5) interacts with GABARAP proteins and mediates membrane localization of UBA5.
Stimulates transfer of UFM1 from UBA5 to the E2, UFC1.
Title: An N-Terminal Extension to UBA5 Adenylation Domain Boosts UFM1 Activation: Isoform-Specific Differences in Ubiquitin-like Protein Activation.
Likely pathogenic variants were identified in SOX5 gene, not previously associated with epilepsy, and UBA5, a recently associated with epilepsy gene
Title: Diagnostic exome sequencing of syndromic epilepsy patients in clinical practice.
our results further demonstrate the importance of post-translational modifications such as the addition of an ubiquitin-fold modifier 1 (UFM1) to target proteins (ufmylation) for normal neuronal networks activity, and reveal that the dysfunction of the ubiquitous UBA5 protein is a cause of EME.
Title: Abnormal function of the UBA5 protein in a case of early developmental and epileptic encephalopathy with suppression-burst.

Submit: New GeneRIF Correction See all GeneRIFs (24)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Developmental and epileptic encephalopathy, 44 MedGen: C4310700 OMIM: 617132 GeneReviews: Not available	Compare labs
Spinocerebellar ataxia, autosomal recessive 24 MedGen: C4310699 OMIM: 617133 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-35962 (e-PCR)
- UniSTS:80904

STS-H07121 (e-PCR)
- UniSTS:72122

STS-Z40704 (e-PCR)
- UniSTS:78042

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables UFM1 activating enzyme activity	IBA Inferred from Biological aspect of Ancestor more info
enables UFM1 activating enzyme activity	IDA Inferred from Direct Assay more info	PubMed
enables UFM1 activating enzyme activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	IDA Inferred from Direct Assay more info	PubMed
enables zinc ion binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in erythrocyte differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in localization	IDA Inferred from Direct Assay more info	PubMed
involved_in megakaryocyte differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in neuromuscular process	IGI Inferred from Genetic Interaction more info	PubMed
involved_in protein K69-linked ufmylation	IDA Inferred from Direct Assay more info	PubMed
involved_in protein ufmylation	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein ufmylation	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within protein ufmylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein ufmylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of intracellular estrogen receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within response to endoplasmic reticulum stress	IDA Inferred from Direct Assay more info	PubMed
involved_in response to endoplasmic reticulum stress	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in reticulophagy	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in Golgi apparatus	IEA Inferred from Electronic Annotation more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IDA Inferred from Direct Assay more info
located_in endoplasmic reticulum membrane	IDA Inferred from Direct Assay more info	PubMed
located_in intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info
located_in nucleus	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: ubiquitin-like modifier-activating enzyme 5

Names: UBA5, ubiquitin-activating enzyme E1 homolog; UFM1-activating enzyme; ubiquitin-activating enzyme 5; ubiquitin-activating enzyme E1 domain-containing protein 1; ubiquitin-activating enzyme E1-domain containing 1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_052968.1 RefSeqGene

Range

10884..30349

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001320210.2 → NP_001307139.1 ubiquitin-like modifier-activating enzyme 5 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses an alternate 5' terminal exon, resulting in a distinct 5' UTR and the use of a downstream start codon, compared to variant 1. The encoded isoform (2) has a shorter N-terminus compared to isoform 1. Variants 2 and 3 encode the same isoform.

Source sequence(s)

AC020632, AC055732, AI681654, AK026904, BC048015, BI562266, BX537742

Consensus CDS

CCDS3077.1

UniProtKB/TrEMBL

E7EQ61

Related

ENSP00000418807.2, ENST00000494238.6

Conserved Domains (2) summary

cd00757
Location:1 → 241

ThiF_MoeB_HesA_family; ThiF_MoeB_HesA. Family of E1-like enzymes involved in molybdopterin and thiamine biosynthesis family. The common reaction mechanism catalyzed by MoeB and ThiF, like other E1 enzymes, begins with a nucleophilic attack of the C-terminal carboxylate of MoaD ...

pfam00899
Location:12 → 253

ThiF; ThiF family
NM_001321238.2 → NP_001308167.1 ubiquitin-like modifier-activating enzyme 5 isoform 3

Status: REVIEWED

Source sequence(s)

AC020632, AC055732, AI681654, AY253672, BI562266

UniProtKB/Swiss-Prot

Q9GZZ9

Conserved Domains (2) summary

cd00757
Location:9 → 207

ThiF_MoeB_HesA_family; ThiF_MoeB_HesA. Family of E1-like enzymes involved in molybdopterin and thiamine biosynthesis family. The common reaction mechanism catalyzed by MoeB and ThiF, like other E1 enzymes, begins with a nucleophilic attack of the C-terminal carboxylate of MoaD ...

pfam00899
Location:9 → 219

ThiF; ThiF family
NM_001321239.1 → NP_001308168.1 ubiquitin-like modifier-activating enzyme 5 isoform 4

Status: REVIEWED

Source sequence(s)

AI681654, AK056238, AY253672, DA042045, DA477833, DA785394

UniProtKB/Swiss-Prot

Q9GZZ9

Conserved Domains (2) summary

pfam00899
Location:1 → 197

ThiF; ThiF family

cl22428
Location:1 → 185

E1_enzyme_family; Superfamily of activating enzymes (E1) of the ubiquitin-like proteins. This family includes classical ubiquitin-activating enzymes E1, ubiquitin-like (ubl) activating enzymes and other mechanistic homologes, like MoeB, Thif1 and others. The common ...
NM_024818.6 → NP_079094.1 ubiquitin-like modifier-activating enzyme 5 isoform 1

See identical proteins and their annotated locations for NP_079094.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

AC020632, AC055732, AI681654, AK056238, AY253672

Consensus CDS

CCDS3076.1

UniProtKB/Swiss-Prot

A6NJL3, D3DNC8, Q96ST1, Q9GZZ9

UniProtKB/TrEMBL

E7EQ61

Related

ENSP00000348565.4, ENST00000356232.10

Conserved Domains (1) summary

cd00757
Location:52 → 297

ThiF_MoeB_HesA_family; ThiF_MoeB_HesA. Family of E1-like enzymes involved in molybdopterin and thiamine biosynthesis family. The common reaction mechanism catalyzed by MoeB and ThiF, like other E1 enzymes, begins with a nucleophilic attack of the C-terminal carboxylate of MoaD ...
NM_198329.4 → NP_938143.1 ubiquitin-like modifier-activating enzyme 5 isoform 2

See identical proteins and their annotated locations for NP_938143.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate 5' terminal exon, resulting in a distinct 5' UTR and the use of a downstream start codon, compared to variant 1. The encoded isoform (2) has a shorter N-terminus compared to isoform 1. Variants 2 and 3 encode the same isoform.

Source sequence(s)

AC020632, AC055732, AI681654, AY253672, BQ581736, DB457433

Consensus CDS

CCDS3077.1

UniProtKB/TrEMBL

E7EQ61

Related

ENSP00000264991.4, ENST00000264991.8

Conserved Domains (2) summary

cd00757
Location:1 → 241

ThiF_MoeB_HesA_family; ThiF_MoeB_HesA. Family of E1-like enzymes involved in molybdopterin and thiamine biosynthesis family. The common reaction mechanism catalyzed by MoeB and ThiF, like other E1 enzymes, begins with a nucleophilic attack of the C-terminal carboxylate of MoaD ...

pfam00899
Location:12 → 253

ThiF; ThiF family