Human Gene UBE2D3 (uc003hwl.3) Description and Page Index
  Description: Homo sapiens ubiquitin-conjugating enzyme E2D 3 (UBE2D3), transcript variant 7, mRNA.
RefSeq Summary (NM_181891): 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 E2 ubiquitin-conjugating enzyme family. This enzyme functions in the ubiquitination of the tumor-suppressor protein p53, which is induced by an E3 ubiquitin-protein ligase. [provided by RefSeq, Jan 2017].
Transcript (Including UTRs)
   Position: hg19 chr4:103,717,133-103,748,708 Size: 31,576 Total Exon Count: 8 Strand: -
Coding Region
   Position: hg19 chr4:103,718,572-103,747,665 Size: 29,094 Coding Exon Count: 7 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr4:103,717,133-103,748,708)mRNA (may differ from genome)Protein (147 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
OMIMPubMedReactomeStanford SOURCEUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Ubiquitin-conjugating enzyme E2 D3; EC=; AltName: Full=Ubiquitin carrier protein D3; AltName: Full=Ubiquitin-conjugating enzyme E2(17)KB 3; AltName: Full=Ubiquitin-conjugating enzyme E2-17 kDa 3; AltName: Full=Ubiquitin-protein ligase D3;
FUNCTION: Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys- 11'-, as well as 'Lys-48'-linked polyubiquitination. Cooperates with the E2 CDC34 and the SCF(FBXW11) E3 ligase complex for the polyubiquitination of NFKBIA leading to its subsequent proteasomal degradation. Acts as an initiator E2, priming the phosphorylated NFKBIA target at positions 'Lys-21' and/or 'Lys-22' with a monoubiquitin. Ubiquitin chain elongation is then performed by CDC34, building ubiquitin chains from the UBE2D3-primed NFKBIA- linked ubiquitin. Acts also as an initiator E2, in conjunction with RNF8, for the priming of PCNA. Monoubiquitination of PCNA, and its subsequent polyubiquitination, are essential events in the operation of the DNA damage tolerance (DDT) pathway that is activated after DNA damage caused by UV or chemical agents during S-phase. Associates with the BRCA1/BARD1 E3 ligase complex to perform ubiquitination at DNA damage sites following ionizing radiation leading to DNA repair. Targets DAPK3 for ubiquitination which influences promyelocytic leukemia protein nuclear body (PML- NB) formation in the nucleus. In conjunction with the MDM2 and TOPORS E3 ligases, functions ubiquitination of p53/TP53. Supports NRDP1-mediated ubiquitination and degradation of ERBB3 and of BRUCE which triggers apoptosis. In conjunction with the CBL E3 ligase, targets EGFR for polyubiquitination at the plasma membrane as well as during its internalization and transport on endosomes. In conjunction with the STUB1 E3 quality control E3 ligase, ubiquitinates unfolded proteins to catalyze their immediate destruction (By similarity).
CATALYTIC ACTIVITY: ATP + ubiquitin + protein lysine = AMP + diphosphate + protein N-ubiquityllysine.
PATHWAY: Protein modification; protein ubiquitination.
SUBUNIT: Interacts with SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex; when Cullin is neddylated, the interaction between the E2 and the SCF complex is strengthened. Interacts with DAPK3. Interacts with BRCA1; the DNA damage checkpoint promotes the association with BRCA1 after ionizing radiation. Interacts non- covalently with ubiquitin.
INTERACTION: Q9Y3C5:RNF11; NbExp=3; IntAct=EBI-348268, EBI-396669; Q9BV68:RNF126; NbExp=3; IntAct=EBI-348268, EBI-357322; Q68DV7:RNF43; NbExp=2; IntAct=EBI-348268, EBI-1647060; Q99942:RNF5; NbExp=3; IntAct=EBI-348268, EBI-348482; Q9Y4K3:TRAF6; NbExp=2; IntAct=EBI-348268, EBI-359276; P98170:XIAP; NbExp=2; IntAct=EBI-348268, EBI-517127; Q8ND25:ZNRF1; NbExp=3; IntAct=EBI-348268, EBI-2129250;
SUBCELLULAR LOCATION: Cell membrane; Peripheral membrane protein. Endosome membrane; Peripheral membrane protein.
SIMILARITY: Belongs to the ubiquitin-conjugating enzyme family.

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): UBE2D3
CDC HuGE Published Literature: UBE2D3
Positive Disease Associations: Diabetes Mellitus
Related Studies:
  1. Diabetes Mellitus
    , , . [PubMed 0]

-  MalaCards Disease Associations
  MalaCards Gene Search: UBE2D3
Diseases sorted by gene-association score: retinitis pigmentosa 42 (2)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 67.11 RPKM in Cells - EBV-transformed lymphocytes
Total median expression: 2116.08 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -107.03253-0.423 Picture PostScript Text
3' UTR -381.241439-0.265 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000608 - UBQ-conjugat_E2
IPR023313 - UBQ-conjugating_AS
IPR016135 - UBQ-conjugating_enzyme/RWD

Pfam Domains:
PF00179 - Ubiquitin-conjugating enzyme

SCOP Domains:
54495 - UBC-like

Protein Data Bank (PDB) 3-D Structure
MuPIT help

- X-ray MuPIT


- X-ray MuPIT
To conserve bandwidth, only the images from the first 3 structures are shown.
3RPG - X-ray MuPIT 3UGB - X-ray MuPIT

ModBase Predicted Comparative 3D Structure on P61077
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0004842 ubiquitin-protein transferase activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0016740 transferase activity
GO:0061631 ubiquitin conjugating enzyme activity

Biological Process:
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0000209 protein polyubiquitination
GO:0006281 DNA repair
GO:0006464 cellular protein modification process
GO:0006511 ubiquitin-dependent protein catabolic process
GO:0006513 protein monoubiquitination
GO:0006625 protein targeting to peroxisome
GO:0006915 apoptotic process
GO:0006974 cellular response to DNA damage stimulus
GO:0016567 protein ubiquitination
GO:0030509 BMP signaling pathway
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
GO:0051865 protein autoubiquitination
GO:0070936 protein K48-linked ubiquitination
GO:0070979 protein K11-linked ubiquitination
GO:1903955 positive regulation of protein targeting to mitochondrion

Cellular Component:
GO:0005654 nucleoplasm
GO:0005768 endosome
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0010008 endosome membrane
GO:0016020 membrane
GO:0070062 extracellular exosome

-  Descriptions from all associated GenBank mRNAs
  BC037894 - Homo sapiens ubiquitin-conjugating enzyme E2D 3 (UBC4/5 homolog, yeast), mRNA (cDNA clone MGC:43926 IMAGE:5275356), complete cds.
JD503133 - Sequence 484157 from Patent EP1572962.
JD352321 - Sequence 333345 from Patent EP1572962.
JD170942 - Sequence 151966 from Patent EP1572962.
AK127304 - Homo sapiens cDNA FLJ45372 fis, clone BRHIP3018278, highly similar to Ubiquitin-conjugating enzyme E2-17 kDa 3 (EC
AK095822 - Homo sapiens cDNA FLJ38503 fis, clone HCHON2000056, highly similar to UBIQUITIN-CONJUGATING ENZYME E2-17 KDA 3 (EC
AL050186 - Homo sapiens mRNA; cDNA DKFZp586A0723 (from clone DKFZp586A0723).
JD155647 - Sequence 136671 from Patent EP1572962.
JD353756 - Sequence 334780 from Patent EP1572962.
JD375498 - Sequence 356522 from Patent EP1572962.
JD312662 - Sequence 293686 from Patent EP1572962.
BC066917 - Homo sapiens ubiquitin-conjugating enzyme E2D 3 (UBC4/5 homolog, yeast), mRNA (cDNA clone MGC:87126 IMAGE:4792462), complete cds.
BC003395 - Homo sapiens ubiquitin-conjugating enzyme E2D 3 (UBC4/5 homolog, yeast), mRNA (cDNA clone MGC:5416 IMAGE:3447673), complete cds.
JD313060 - Sequence 294084 from Patent EP1572962.
JD271521 - Sequence 252545 from Patent EP1572962.
JD258028 - Sequence 239052 from Patent EP1572962.
AL833414 - Homo sapiens mRNA; cDNA DKFZp313K1222 (from clone DKFZp313K1222).
U39318 - Human E2 ubiquitin conjugating enzyme UbcH5C (UBCH5C) mRNA, complete cds.
JD073252 - Sequence 54276 from Patent EP1572962.
JD288597 - Sequence 269621 from Patent EP1572962.
JD301242 - Sequence 282266 from Patent EP1572962.
AK315775 - Homo sapiens cDNA, FLJ96889.
KJ904583 - Synthetic construct Homo sapiens clone ccsbBroadEn_13977 UBE2D3-like gene, encodes complete protein.
KJ897720 - Synthetic construct Homo sapiens clone ccsbBroadEn_07114 UBE2D3 gene, encodes complete protein.
AB529202 - Synthetic construct DNA, clone: pF1KB5476, Homo sapiens UBE2D3 gene for ubiquitin-conjugating enzyme E2D 3, without stop codon, in Flexi system.
CR456916 - Homo sapiens full open reading frame cDNA clone RZPDo834H1015D for gene UBE2D3, ubiquitin-conjugating enzyme E2D 3 (UBC4/5 homolog, yeast); complete cds, incl. stopcodon.
AF116686 - Homo sapiens PRO2116 mRNA, complete cds.
LF380945 - JP 2014500723-A/188448: Polycomb-Associated Non-Coding RNAs.
JD059312 - Sequence 40336 from Patent EP1572962.
JD056101 - Sequence 37125 from Patent EP1572962.
JD454365 - Sequence 435389 from Patent EP1572962.
JD474382 - Sequence 455406 from Patent EP1572962.
JD494041 - Sequence 475065 from Patent EP1572962.
JD136966 - Sequence 117990 from Patent EP1572962.
JD474381 - Sequence 455405 from Patent EP1572962.
MA616522 - JP 2018138019-A/188448: Polycomb-Associated Non-Coding RNAs.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04120 - Ubiquitin mediated proteolysis

Reactome (by CSHL, EBI, and GO)

Protein P61077 (Reactome details) participates in the following event(s):

R-HSA-1234172 Nuclear VBC complex ubiquitinylates HIF-alpha
R-HSA-1234163 Cytosolic VBC complex ubiquitinylates hydroxyprolyl-HIF-alpha
R-HSA-8953946 PEX2:PEX10:PEX12 monoubiquitinates PEX5S,L at cysteine-11
R-HSA-8956106 VHL:EloB,C:NEDD8-CUL2:RBX1 complex ubiquitinylates HIF-alpha
R-HSA-9033485 PEX2:PEX10:PEX12 monoubiquitinates PEX5L at cysteine-11
R-HSA-983152 Transfer of ubiquitin from E1 to E2
R-HSA-983140 Transfer of Ub from E2 to substrate and release of E2
R-HSA-983157 Interaction of E3 with substrate and E2-Ub complex
R-HSA-8939323 RNF181 binds BCL10 and Ubiquitin:E2
R-HSA-8953917 PEX2:PEX10:PEX12 binds PEX5S,L (in PEX5S:PEX13:PEX14) and Ub:UBE2D1,2,3
R-HSA-9033527 PEX2:PEX10:PEX12 binds PEX5L (in PEX5L:PEX7:PEX13:PEX14:PEX2:PEX10:PEX12) and Ub:UBE2D1,2,3
R-HSA-168915 K63-linked ubiquitination of RIP1 bound to the activated TLR complex
R-HSA-9014342 K63-linked ubiquitination of RIP1 bound to the activated TLR complex
R-HSA-1234176 Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha
R-HSA-936440 Negative regulators of DDX58/IFIH1 signaling
R-HSA-8866654 E3 ubiquitin ligases ubiquitinate target proteins
R-HSA-9033241 Peroxisomal protein import
R-HSA-8951664 Neddylation
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
R-HSA-2173795 Downregulation of SMAD2/3:SMAD4 transcriptional activity
R-HSA-201451 Signaling by BMP
R-HSA-1234174 Regulation of Hypoxia-inducible Factor (HIF) by oxygen
R-HSA-168928 DDX58/IFIH1-mediated induction of interferon-alpha/beta
R-HSA-8852135 Protein ubiquitination
R-HSA-392499 Metabolism of proteins
R-HSA-597592 Post-translational protein modification
R-HSA-983169 Class I MHC mediated antigen processing & presentation
R-HSA-2173793 Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer
R-HSA-9006936 Signaling by TGF-beta family members
R-HSA-2262749 Cellular response to hypoxia
R-HSA-168249 Innate Immune System
R-HSA-1280218 Adaptive Immune System
R-HSA-170834 Signaling by TGF-beta Receptor Complex
R-HSA-212436 Generic Transcription Pathway
R-HSA-162582 Signal Transduction
R-HSA-2262752 Cellular responses to stress
R-HSA-168256 Immune System
R-HSA-73857 RNA Polymerase II Transcription
R-HSA-8953897 Cellular responses to external stimuli
R-HSA-937041 IKK complex recruitment mediated by RIP1
R-HSA-168927 TICAM1, RIP1-mediated IKK complex recruitment
R-HSA-74160 Gene expression (Transcription)
R-HSA-937061 TRIF(TICAM1)-mediated TLR4 signaling
R-HSA-168164 Toll Like Receptor 3 (TLR3) Cascade
R-HSA-166166 MyD88-independent TLR4 cascade
R-HSA-168898 Toll-Like Receptors Cascades
R-HSA-166016 Toll Like Receptor 4 (TLR4) Cascade

-  Other Names for This Gene
  Alternate Gene Symbols: A6NJ93, A6NJB1, A6NM99, NM_181891, NP_871620, P47986, P61077, Q6IB88, Q6NXS4, Q8N924, UB2D3_HUMAN, UBC5C, UBCH5C
UCSC ID: uc003hwl.3
RefSeq Accession: NM_181891
Protein: P61077 (aka UB2D3_HUMAN or UB5C_HUMAN)
CCDS: CCDS3660.1

-  Gene Model Information
category: coding nonsense-mediated-decay: no RNA accession: NM_181891.1
exon count: 8CDS single in 3' UTR: no RNA size: 2151
ORF size: 444CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 1088.00frame shift in genome: no % Coverage: 99.30
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.