UBA3 ubiquitin like modifier activating enzyme 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: UBA3provided by HGNC
Official Full Name: ubiquitin like modifier activating enzyme 3provided by HGNC
Primary source: HGNC:HGNC:12470
See related: Ensembl:ENSG00000144744 MIM:603172; AllianceGenome:HGNC:12470
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: NAE2; UBE1C; hUBA3
Summary: 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]
Expression: Ubiquitous expression in heart (RPKM 24.5), lymph node (RPKM 24.0) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 3p14.1

Exon count:: 18

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (69054730..69080373, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (69091517..69117165, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (69103881..69129524, complement)

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?

UBA3 promotes the occurrence and metastasis of intrahepatic cholangiocarcinoma through MAPK signaling pathway.
Title: UBA3 promotes the occurrence and metastasis of intrahepatic cholangiocarcinoma through MAPK signaling pathway.
The NEDD8-activating enzyme E1 UBA3 orchestrates the immunosuppressive microenvironment in lung adenocarcinoma via the NF-small ka, CyrillicB pathway.
Title: The NEDD8-activating enzyme E1 UBA3 orchestrates the immunosuppressive microenvironment in lung adenocarcinoma via the NF-кB pathway.
UBE1C is upregulated and promotes neddylation of p53 in lung cancer.
Title: UBE1C is upregulated and promotes neddylation of p53 in lung cancer.
The study demonstrated that two mutations in UBA3 which were not previously reported confer MLN4924 resistance to MLN4924, a selective NEDD8-activating enzyme inhibitor.
Title: Mutations in UBA3 confer resistance to the NEDD8-activating enzyme inhibitor MLN4924 in human leukemic cells.
E1 (NAE1 and UBA3) and E2 (UBC12) enzymes, as well as global NEDD8 conjugation, were upregulated in over 2/3 of human intrahepatic cholangiocarcinoma
Title: Neddylation pathway is up-regulated in human intrahepatic cholangiocarcinoma and serves as a potential therapeutic target.
Report role for neddylation via Nedd8-activating enzyme in the regulation of tumor angiogenesis.
Title: Suppression of tumor angiogenesis by targeting the protein neddylation pathway.
Demonstrated that Uba3-betaGD is an independently folded domain in solution and that residues involved in E2 binding are absent from the NMR spectrum, indicating that the E2-binding surface on Uba3-betaGD interconverts between multiple conformations.
Title: E2-binding surface on Uba3 β-grasp domain undergoes a conformational transition.
X-ray crystallographic analysis of APPBP1-UBA3-NEDD8 shows that APPBP1-UBA3's preference for NEDD8's Ala72 appears to be indirect, due to proper positioning of UBA3's Arg190.
Title: Structural dissection of a gating mechanism preventing misactivation of ubiquitin by NEDD8's E1.
Conservation in the mechanism of Nedd8 activation by the human AppBp1-Uba3 heterodimer.
Title: Conservation in the mechanism of Nedd8 activation by the human AppBp1-Uba3 heterodimer.
structure and mutational analysis of human APPBP1-UBA3, the heterodimeric E1 enzyme for NEDD8
Title: Insights into the ubiquitin transfer cascade from the structure of the activating enzyme for NEDD8.

Submit: New GeneRIF Correction See all GeneRIFs (12)

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of ubiquitin-like modifier activating enzyme 3 (UBA3) by siRNA inhibits HIV-1 replication in CD4+/CCR5+/CXCR4+ TZM-bl HeLa cells	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

A005V36 (e-PCR)
- UniSTS:20747

G32297 (e-PCR)
- UniSTS:116893

SHGC-77074 (e-PCR)
- UniSTS:58017

WI-12011 (e-PCR)
- UniSTS:5343

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
contributes_to NEDD8 activating enzyme activity	IDA Inferred from Direct Assay more info	PubMed
enables NEDD8 activating enzyme activity	IDA Inferred from Direct Assay more info	PubMed
enables NEDD8 transferase activity	TAS Traceable Author Statement more info
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein heterodimerization activity	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in endomitotic cell cycle	IEA Inferred from Electronic Annotation more info
involved_in post-translational protein modification	TAS Traceable Author Statement more info
involved_in protein modification process	TAS Traceable Author Statement more info	PubMed
involved_in protein neddylation	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein neddylation	IDA Inferred from Direct Assay more info	PubMed
involved_in protein neddylation	IEA Inferred from Electronic Annotation more info
involved_in proteolysis	TAS Traceable Author Statement more info	PubMed
involved_in regulation of cell cycle	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: NEDD8-activating enzyme E1 catalytic subunit

Names: NEDD8-activating enzyme E1 subunit 2; NEDD8-activating enzyme E1C; Nedd8-activating enzyme hUba3; UBA3, ubiquitin-activating enzyme E1 homolog; ubiquitin-activating enzyme 3; ubiquitin-activating enzyme E1C (UBA3 homolog, yeast); ubiquitin-activating enzyme E1C (homologous to yeast UBA3)

NP_001350790.1

EC 6.2.1.64

NP_003959.3

EC 6.2.1.64

NP_937838.1

EC 6.2.1.64

XP_011532512.1

EC 6.2.1.64

XP_054204301.1

EC 6.2.1.64

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.

mRNA and Protein(s)

NM_001363861.1 → NP_001350790.1 NEDD8-activating enzyme E1 catalytic subunit isoform 3

Status: REVIEWED

Source sequence(s)

AC092060, AC109587

Consensus CDS

CCDS87106.1

UniProtKB/TrEMBL

B2RBP3, F8W8D4

Related

ENSP00000400294.2, ENST00000415609.6

Conserved Domains (2) summary

cd01488
Location:48 → 327

Uba3_RUB; Ubiquitin activating enzyme (E1) subunit UBA3. UBA3 is part of the heterodimeric activating enzyme (E1), specific for the Rub family of ubiquitin-like proteins (Ubls). E1 enzymes are part of a conjugation cascade to attach Ub or Ubls, covalently to ...

pfam08825
Location:335 → 420

E2_bind; E2 binding domain
NM_003968.4 → NP_003959.3 NEDD8-activating enzyme E1 catalytic subunit isoform 1

See identical proteins and their annotated locations for NP_003959.3

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1).

Source sequence(s)

AK002159, AL117566, BC022853, CD700642

Consensus CDS

CCDS2909.1

UniProtKB/Swiss-Prot

A6NLB5, A8K027, O76088, Q8TBC4, Q9NTU3

UniProtKB/TrEMBL

B2RBP3

Related

ENSP00000354340.4, ENST00000361055.9

Conserved Domains (2) summary

cd01488
Location:71 → 368

Uba3_RUB; Ubiquitin activating enzyme (E1) subunit UBA3. UBA3 is part of the heterodimeric activating enzyme (E1), specific for the Rub family of ubiquitin-like proteins (Ubls). E1 enzymes are part of a conjugation cascade to attach Ub or Ubls, covalently to ...

pfam08825
Location:376 → 461

E2_bind; E2 binding domain
NM_198195.2 → NP_937838.1 NEDD8-activating enzyme E1 catalytic subunit isoform 2

See identical proteins and their annotated locations for NP_937838.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an in-frame exon in the 5' coding region, as compared to variant 1. The encoded isoform (2) is thus missing an internal segment in the N-terminal region, as compared to isoform 1.

Source sequence(s)

AK002159, AL117566, CD700642

Consensus CDS

CCDS2910.1

UniProtKB/TrEMBL

B2RBP3

Related

ENSP00000340041.4, ENST00000349511.8

Conserved Domains (2) summary

cd01488
Location:57 → 354

Uba3_RUB; Ubiquitin activating enzyme (E1) subunit UBA3. UBA3 is part of the heterodimeric activating enzyme (E1), specific for the Rub family of ubiquitin-like proteins (Ubls). E1 enzymes are part of a conjugation cascade to attach Ub or Ubls, covalently to ...

pfam08825
Location:362 → 447

E2_bind; E2 binding domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000003.12 Reference GRCh38.p14 Primary Assembly

Range

69054730..69080373 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011534210.2 → XP_011532512.1 NEDD8-activating enzyme E1 catalytic subunit isoform X1

See identical proteins and their annotated locations for XP_011532512.1

UniProtKB/TrEMBL

B2RBP3

Conserved Domains (2) summary

cd01488
Location:62 → 341

Uba3_RUB; Ubiquitin activating enzyme (E1) subunit UBA3. UBA3 is part of the heterodimeric activating enzyme (E1), specific for the Rub family of ubiquitin-like proteins (Ubls). E1 enzymes are part of a conjugation cascade to attach Ub or Ubls, covalently to ...

pfam08825
Location:349 → 434

E2_bind; E2 binding domain

Alternate T2T-CHM13v2.0

Genomic

NC_060927.1 Alternate T2T-CHM13v2.0

Range

69091517..69117165 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054348326.1 → XP_054204301.1 NEDD8-activating enzyme E1 catalytic subunit isoform X1

UniProtKB/TrEMBL

B2RBP3

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_198197.1: Suppressed sequence

Description

NM_198197.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.