UBE2D2 ubiquitin conjugating enzyme E2 D2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: UBE2D2provided by HGNC
Official Full Name: ubiquitin conjugating enzyme E2 D2provided by HGNC
Primary source: HGNC:HGNC:12475
See related: Ensembl:ENSG00000131508 MIM:602962; AllianceGenome:HGNC:12475
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: UBC4; PUBC1; UBCH4; UBC4/5; UBCH5B; E2(17)KB2
Summary: Regulated degradation of misfolded, damaged or short-lived proteins in eukaryotes occurs via the ubiquitin (Ub)-proteasome system (UPS). An integral part of the UPS system is the ubiquitination of target proteins and covalent linkage of Ub-containing proteins to form polymeric chains, marking them as targets for 26S proteasome-mediated degradation. Ubiquitination of proteins is mediated by a cascade of enzymes which includes E1 (ubiquitin activating), E2 (ubiquitin conjugating), and E3 (ubiquitin ligases) enzymes. This gene encodes a member of the E2 enzyme family. Substrates of this enzyme include the tumor suppressor protein p53 and peroxisomal biogenesis factor 5 (PEX5). Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, May 2013]
Expression: Ubiquitous expression in testis (RPKM 32.5), brain (RPKM 24.1) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 5q31.2

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	5	NC_000005.10 (139526240..139628434)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	5	NC_060929.1 (140086420..140153498)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	5	NC_000005.9 (138940924..139008019)

Chromosome 5 - NC_000005.10 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?

The E2 ubiquitin-conjugating enzymes UBE2D1 and UBE2D2 regulate VEGFR2 dynamics and endothelial function.
Title: The E2 ubiquitin-conjugating enzymes UBE2D1 and UBE2D2 regulate VEGFR2 dynamics and endothelial function.
Exosomes Mediated Transfer of Circ_UBE2D2 Enhances the Resistance of Breast Cancer to Tamoxifen by Binding to MiR-200a-3p.
Title: Exosomes Mediated Transfer of Circ_UBE2D2 Enhances the Resistance of Breast Cancer to Tamoxifen by Binding to MiR-200a-3p.
Ube2D2 was validated as a functional E2 enzyme for the ubiquitylation of the p53 transactivation domain (p53-TAD) by MUL1-RING, and purification and crystallization processes for MUL1-RING and the MUL1-RING-Ube2D2 complex are reported.
Title: The RING domain of mitochondrial E3 ubiquitin ligase 1 and its complex with Ube2D2: crystallization and X-ray diffraction.
results disclose the mechanism by which cIAP1 RING dimer activates UbcH5B approximately Ub and indicate that noncovalent Ubiquitin (Ub) binding further stabilizes the cIAP1-UbcH5B approximately Ubiquitin (Ub) complex in the active conformation to stimulate Ub transfer
Title: Structural insights into non-covalent ubiquitin activation of the cIAP1-UbcH5B∼ubiquitin complex.
These results point to an important role of the affinity between RNF4 and its cognate RAD6B or UBCH5B in governing the multiplicity of substrate ubiquitination.
Title: Role of E2-RING Interactions in Governing RNF4-Mediated Substrate Ubiquitination.
Knockdown of UBE2D2 caused an increase in p53 protein levels, and knockdown of p53 attenuated not only cadmium-induced apoptosis, but also cadmium-induced apoptosis-related gene expression.
Title: Accumulation of p53 via down-regulation of UBE2D family genes is a critical pathway for cadmium-induced renal toxicity.
mutations having marked effects on function only minimally affect the intermolecular interactions between the AO7 RING and UbcH5B, establishing a high degree of complexity in activation through the RING-E2 interface.
Title: Insights into Ubiquitination from the Unique Clamp-like Binding of the RING E3 AO7 to the E2 UbcH5B.
Data show that ubiquitin E2 enzymes UBE2D1/2/3 and E3 ligase RNF138 accumulate at DNA-damage sites and act at early resection stages by promoting CtIP protein ubiquitylation and accrual.
Title: Systematic E2 screening reveals a UBE2D-RNF138-CtIP axis promoting DNA repair.
together with UBE2L3 and UBE2N, synergistically contribute to Parkin-mediated mitophagy
Title: The ubiquitin-conjugating enzymes UBE2N, UBE2L3 and UBE2D2/3 are essential for Parkin-dependent mitophagy.
Presented is the structure of the human dimeric RING domain from BIRC7 in complex with the E2 UbcH5B covalently linked to Ub.
Title: BIRC7-E2 ubiquitin conjugate structure reveals the mechanism of ubiquitin transfer by a RING dimer.

Submit: New GeneRIF Correction See all GeneRIFs (21)

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

EBI GWAS Catalog

Description
Genome-wide analysis of polymorphisms associated with cytokine responses in smallpox vaccine recipients. EBI GWAS Catalog EBI GWAS CatalogPubMed

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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Protein interactions

Protein	Gene	Interaction	Pubs
Vif	vif	CUL5/RBX2/ELOB/ELOC/Vif/CBF-beta complex catalyzes polyubiquitin chain formation on A3G in the presence of ubiquitin E2 UBE2R1 (CDC34) or UBCH5b (UBE2D2)	PubMed
integrase	gag-pol	Analysis of HIV-1 proviral integration sites in antiretroviral treatment patients indicates that UBE2D2 gene favors HIV-1 integration for expansion and persistence of infected cells, suggesting HIV-1 IN interacts with UBE2D2	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D5S1633E (e-PCR)
- UniSTS:69393

WI-13988 (e-PCR)
- UniSTS:4161

bac5252T (e-PCR)
- UniSTS:181575

UBE2D2_1119 (e-PCR)
- UniSTS:277853

D5S1932 (e-PCR)
- UniSTS:32196

PMC166143P1 (e-PCR)
- UniSTS:271559

RH137016 (e-PCR)
- UniSTS:219105

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables ubiquitin conjugating enzyme activity	IBA Inferred from Biological aspect of Ancestor more info
enables ubiquitin conjugating enzyme activity	IDA Inferred from Direct Assay more info	PubMed
enables ubiquitin protein ligase activity	IDA Inferred from Direct Assay more info	PubMed
enables ubiquitin protein ligase binding	IBA Inferred from Biological aspect of Ancestor more info
enables ubiquitin-protein transferase activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in protein K48-linked ubiquitination	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein K48-linked ubiquitination	IDA Inferred from Direct Assay more info	PubMed
involved_in protein autoubiquitination	IDA Inferred from Direct Assay more info	PubMed
involved_in protein modification process	TAS Traceable Author Statement more info	PubMed
involved_in protein polyubiquitination	IDA Inferred from Direct Assay more info	PubMed
involved_in protein ubiquitination	IDA Inferred from Direct Assay more info	PubMed
involved_in ubiquitin-dependent protein catabolic process	IBA Inferred from Biological aspect of Ancestor more info

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

General protein information

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Preferred Names: ubiquitin-conjugating enzyme E2 D2

Names: (E3-independent) E2 ubiquitin-conjugating enzyme D2; E2 ubiquitin-conjugating enzyme D2; p53-regulated ubiquitin-conjugating enzyme 1; ubiquitin carrier protein D2; ubiquitin conjugating enzyme E2D 2; ubiquitin-conjugating enzyme E2-17 kDa 2; ubiquitin-conjugating enzyme E2D 2 (homologous to yeast UBC4/5); ubiquitin-protein ligase D2

NP_003330.1

EC 2.3.2.23

EC 2.3.2.24

NP_862821.1

EC 2.3.2.23

EC 2.3.2.24

XP_047273646.1

EC 2.3.2.23

EC 2.3.2.24

XP_047273647.1

EC 2.3.2.23

EC 2.3.2.24

XP_054209400.1

EC 2.3.2.23

EC 2.3.2.24

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_003339.3 → NP_003330.1 ubiquitin-conjugating enzyme E2 D2 isoform 1

See identical proteins and their annotated locations for NP_003330.1

Status: REVIEWED

Description

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

Source sequence(s)

AF317220, AK001311, AK001428, BC033349

Consensus CDS

CCDS43369.1

UniProtKB/Swiss-Prot

D3DQC9, P51669, P62837, Q3MN78, Q96RP6

UniProtKB/TrEMBL

A0A087WY85

Related

ENSP00000381717.3, ENST00000398733.8

Conserved Domains (1) summary

cl00154
Location:1 → 146

UBCc; Ubiquitin-conjugating enzyme E2, catalytic (UBCc) domain. This is part of the ubiquitin-mediated protein degradation pathway in which a thiol-ester linkage forms between a conserved cysteine and the C-terminus of ubiquitin and complexes with ubiquitin ...
NM_181838.2 → NP_862821.1 ubiquitin-conjugating enzyme E2 D2 isoform 2

See identical proteins and their annotated locations for NP_862821.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) contains an alternate exon in the 5' region, differs in the 5' UTR and initiates translation at a downstream start codon, compared to variant 1. It encodes isoform 2 which is shorter at the N-terminus compared to isoform 1.

Source sequence(s)

AF317220, AK001311, AK001428, BC033349, BC048426, BQ186099

Consensus CDS

CCDS47275.1

UniProtKB/TrEMBL

D6RFM0

Related

ENSP00000513666.1, ENST00000698321.1

Conserved Domains (1) summary

cl00154
Location:1 → 117

UBCc; Ubiquitin-conjugating enzyme E2, catalytic (UBCc) domain. This is part of the ubiquitin-mediated protein degradation pathway in which a thiol-ester linkage forms between a conserved cysteine and the C-terminus of ubiquitin and complexes with ubiquitin ...