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Protein

Ubiquitin-conjugating enzyme E2 D3

Gene

UBE2D3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.14 Publications

Catalytic activityi

S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [E2 ubiquitin-conjugating enzyme]-L-cysteine = [E1 ubiquitin-activating enzyme]-L-cysteine + S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine.PROSITE-ProRule annotation1 Publication
S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E1 ubiquitin-activating enzyme]-L-cysteine + N6-monoubiquitinyl-[acceptor protein]-L-lysine.1 Publication

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.PROSITE-ProRule annotation
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei85Glycyl thioester intermediatePROSITE-ProRule annotation1

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • ubiquitin conjugating enzyme activity Source: ParkinsonsUK-UCL
  • ubiquitin protein ligase binding Source: GO_Central
  • ubiquitin-protein transferase activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionTransferase
Biological processApoptosis, DNA damage, DNA repair, Ubl conjugation pathway
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.3.2.B6 2681
ReactomeiR-HSA-1234176 Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha
R-HSA-168927 TICAM1, RIP1-mediated IKK complex recruitment
R-HSA-201451 Signaling by BMP
R-HSA-2173795 Downregulation of SMAD2/3:SMAD4 transcriptional activity
R-HSA-8866654 E3 ubiquitin ligases ubiquitinate target proteins
R-HSA-8951664 Neddylation
R-HSA-9033241 Peroxisomal protein import
R-HSA-936440 Negative regulators of DDX58/IFIH1 signaling
R-HSA-937041 IKK complex recruitment mediated by RIP1
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
SignaLinkiP61077
SIGNORiP61077
UniPathwayi
UPA00143

Protein family/group databases

MoonDBiP61077 Predicted

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin-conjugating enzyme E2 D3 (EC:2.3.2.231 Publication)
Alternative name(s):
(E3-independent) E2 ubiquitin-conjugating enzyme D3 (EC:2.3.2.241 Publication)
E2 ubiquitin-conjugating enzyme D3
Ubiquitin carrier protein D3
Ubiquitin-conjugating enzyme E2(17)KB 3
Ubiquitin-conjugating enzyme E2-17 kDa 3
Ubiquitin-protein ligase D3
Gene namesi
Name:UBE2D3
Synonyms:UBC5C, UBCH5C
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000109332.19
HGNCiHGNC:12476 UBE2D3
MIMi602963 gene
neXtProtiNX_P61077

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Endosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi77N → S: Activity is restricted HECT-type and not RING-containing E3 ubiquitin-protein ligases. Exhibits ubiquitin transfer with ARIH1 and PRKN. 1 Publication1
Mutagenesisi85C → A: Loss of function. 1 Publication1
Mutagenesisi87D → E or P: Has intermediate lysine reactivity. 1 Publication1
Mutagenesisi87D → K: Abolishes affect lysine reactivity. 1 Publication1
Mutagenesisi87D → N: Does not affect lysine reactivity. 1 Publication1
Mutagenesisi117D → H: Strongly impairs lysine reactivity but retains some ability to transfer ubiquitin to BRCA1. 1 Publication1

Organism-specific databases

DisGeNETi7323
OpenTargetsiENSG00000109332
PharmGKBiPA37126

Polymorphism and mutation databases

DMDMi46577654

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000824661 – 147Ubiquitin-conjugating enzyme E2 D3Add BLAST147

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi21 ↔ 1071 Publication

Post-translational modificationi

Phosphorylated by AURKB.By similarity

Keywords - PTMi

Disulfide bond, Phosphoprotein

Proteomic databases

EPDiP61077
MaxQBiP61077
PeptideAtlasiP61077
PRIDEiP61077
ProteomicsDBi57258
57259 [P61077-2]
57260 [P61077-3]
TopDownProteomicsiP61077-1 [P61077-1]
P61077-2 [P61077-2]

PTM databases

iPTMnetiP61077
PhosphoSitePlusiP61077

Expressioni

Gene expression databases

BgeeiENSG00000109332 Expressed in 234 organ(s), highest expression level in secondary oocyte
CleanExiHS_UBE2D3
ExpressionAtlasiP61077 baseline and differential
GenevisibleiP61077 HS

Organism-specific databases

HPAiHPA003920

Interactioni

Subunit structurei

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. Interacts with E3 ubiquitin-protein ligase CBLC. Interacts with UBTD1 (PubMed:24211586).7 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi113171, 228 interactors
CORUMiP61077
DIPiDIP-29062N
IntActiP61077, 109 interactors
MINTiP61077

Structurei

Secondary structure

1147
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP61077
SMRiP61077
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP61077

Family & Domainsi

Sequence similaritiesi

Belongs to the ubiquitin-conjugating enzyme family.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0417 Eukaryota
COG5078 LUCA
GeneTreeiENSGT00910000143990
HOVERGENiHBG063308
InParanoidiP61077
KOiK06689
OMAiDVYHWQA
OrthoDBiEOG091G0GF8
PhylomeDBiP61077
TreeFamiTF101108

Family and domain databases

CDDicd00195 UBCc, 1 hit
Gene3Di3.10.110.10, 1 hit
InterProiView protein in InterPro
IPR000608 UBQ-conjugat_E2
IPR023313 UBQ-conjugating_AS
IPR016135 UBQ-conjugating_enzyme/RWD
PfamiView protein in Pfam
PF00179 UQ_con, 1 hit
SUPFAMiSSF54495 SSF54495, 1 hit
PROSITEiView protein in PROSITE
PS00183 UBIQUITIN_CONJUGAT_1, 1 hit
PS50127 UBIQUITIN_CONJUGAT_2, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 11 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P61077-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MALKRINKEL SDLARDPPAQ CSAGPVGDDM FHWQATIMGP NDSPYQGGVF
60 70 80 90 100
FLTIHFPTDY PFKPPKVAFT TRIYHPNINS NGSICLDILR SQWSPALTIS
110 120 130 140
KVLLSICSLL CDPNPDDPLV PEIARIYKTD RDKYNRISRE WTQKYAM
Length:147
Mass (Da):16,687
Last modified:April 26, 2004 - v1
Checksum:iADD74A8A708EFEE3
GO
Isoform 2 (identifier: P61077-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     134-147: YNRISREWTQKYAM → YNRLAREWTEKYAML

Show »
Length:148
Mass (Da):16,785
Checksum:iE73DC194DB6D4EFE
GO
Isoform 3 (identifier: P61077-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-8: MALKRINK → MLSNRKCLSK

Show »
Length:149
Mass (Da):16,893
Checksum:iF20F36FCD312444A
GO

Computationally mapped potential isoform sequencesi

There are 11 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D6RAH7D6RAH7_HUMAN
Ubiquitin-conjugating enzyme E2 D3
UBE2D3
118Annotation score:
D6RAW0D6RAW0_HUMAN
Ubiquitin-conjugating enzyme E2 D3
UBE2D3
72Annotation score:
H9KV45H9KV45_HUMAN
Ubiquitin-conjugating enzyme E2 D3
UBE2D3
141Annotation score:
D6RA11D6RA11_HUMAN
Ubiquitin-conjugating enzyme E2 D3
UBE2D3
96Annotation score:
A0A087WY85A0A087WY85_HUMAN
Ubiquitin-conjugating enzyme E2 D3
UBE2D3
148Annotation score:
D6RIZ3D6RIZ3_HUMAN
Ubiquitin-conjugating enzyme E2 D3
UBE2D3
78Annotation score:
D6RGD0D6RGD0_HUMAN
Ubiquitin-conjugating enzyme E2 D3
UBE2D3
49Annotation score:
D6R980D6R980_HUMAN
Ubiquitin-conjugating enzyme E2 D3
UBE2D3
55Annotation score:
D6R933D6R933_HUMAN
Ubiquitin-conjugating enzyme E2 D3
UBE2D3
48Annotation score:
D6R9F6D6R9F6_HUMAN
Ubiquitin-conjugating enzyme E2 D3
UBE2D3
35Annotation score:
There is more potential isoformShow all

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti50Missing in DB045280 (PubMed:14702039).Curated1
Sequence conflicti123I → L in AAH66917 (PubMed:15489334).Curated1
Sequence conflicti137I → V in CAG33197 (PubMed:14702039).Curated1
Sequence conflicti147M → I in CAG33197 (PubMed:14702039).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0380961 – 8MALKRINK → MLSNRKCLSK in isoform 3. 1 Publication8
Alternative sequenceiVSP_038097134 – 147YNRIS…QKYAM → YNRLAREWTEKYAML in isoform 2. 1 PublicationAdd BLAST14

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U39318 mRNA Translation: AAA91461.1
AF213884 Genomic DNA Translation: AAF35234.1
AK095822 mRNA Translation: BAC04632.1
DB045280 mRNA No translation available.
CR456916 mRNA Translation: CAG33197.1
AC018797 Genomic DNA No translation available.
CH471057 Genomic DNA Translation: EAX06138.1
CH471057 Genomic DNA Translation: EAX06143.1
BC003395 mRNA Translation: AAH03395.1
BC037894 mRNA Translation: AAH37894.1
BC066917 mRNA Translation: AAH66917.1
CCDSiCCDS3659.1 [P61077-3]
CCDS3660.1 [P61077-1]
CCDS3661.1 [P61077-2]
RefSeqiNP_003331.1, NM_003340.6 [P61077-1]
NP_871615.1, NM_181886.3 [P61077-1]
NP_871616.1, NM_181887.2 [P61077-1]
NP_871617.1, NM_181888.3 [P61077-1]
NP_871618.1, NM_181889.2 [P61077-1]
NP_871619.1, NM_181890.2 [P61077-1]
NP_871620.1, NM_181891.2 [P61077-1]
NP_871621.1, NM_181892.3 [P61077-2]
NP_871622.1, NM_181893.2 [P61077-3]
UniGeneiHs.518773
Hs.595430
Hs.621366

Genome annotation databases

EnsembliENST00000321805; ENSP00000318494; ENSG00000109332 [P61077-1]
ENST00000338145; ENSP00000337208; ENSG00000109332 [P61077-1]
ENST00000343106; ENSP00000345285; ENSG00000109332 [P61077-2]
ENST00000349311; ENSP00000344069; ENSG00000109332 [P61077-1]
ENST00000357194; ENSP00000349722; ENSG00000109332 [P61077-3]
ENST00000394801; ENSP00000378280; ENSG00000109332 [P61077-1]
ENST00000394803; ENSP00000378282; ENSG00000109332 [P61077-1]
ENST00000394804; ENSP00000378283; ENSG00000109332 [P61077-1]
ENST00000453744; ENSP00000396901; ENSG00000109332 [P61077-1]
GeneIDi7323
KEGGihsa:7323
UCSCiuc003hwi.5 human [P61077-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U39318 mRNA Translation: AAA91461.1
AF213884 Genomic DNA Translation: AAF35234.1
AK095822 mRNA Translation: BAC04632.1
DB045280 mRNA No translation available.
CR456916 mRNA Translation: CAG33197.1
AC018797 Genomic DNA No translation available.
CH471057 Genomic DNA Translation: EAX06138.1
CH471057 Genomic DNA Translation: EAX06143.1
BC003395 mRNA Translation: AAH03395.1
BC037894 mRNA Translation: AAH37894.1
BC066917 mRNA Translation: AAH66917.1
CCDSiCCDS3659.1 [P61077-3]
CCDS3660.1 [P61077-1]
CCDS3661.1 [P61077-2]
RefSeqiNP_003331.1, NM_003340.6 [P61077-1]
NP_871615.1, NM_181886.3 [P61077-1]
NP_871616.1, NM_181887.2 [P61077-1]
NP_871617.1, NM_181888.3 [P61077-1]
NP_871618.1, NM_181889.2 [P61077-1]
NP_871619.1, NM_181890.2 [P61077-1]
NP_871620.1, NM_181891.2 [P61077-1]
NP_871621.1, NM_181892.3 [P61077-2]
NP_871622.1, NM_181893.2 [P61077-3]
UniGeneiHs.518773
Hs.595430
Hs.621366

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1X23X-ray1.85A/B/C/D1-147[»]
2FUHNMR-A2-147[»]
3L1ZX-ray3.17A1-147[»]
3RPGX-ray2.65A2-147[»]
3UGBX-ray2.35A1-147[»]
4BVUX-ray2.70B1-147[»]
4R8PX-ray3.28L/N2-147[»]
4S3OX-ray2.00A/D2-147[»]
5EGGX-ray1.76A1-147[»]
5IFRX-ray2.20A2-147[»]
6CP0X-ray3.01B1-147[»]
ProteinModelPortaliP61077
SMRiP61077
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113171, 228 interactors
CORUMiP61077
DIPiDIP-29062N
IntActiP61077, 109 interactors
MINTiP61077

Protein family/group databases

MoonDBiP61077 Predicted

PTM databases

iPTMnetiP61077
PhosphoSitePlusiP61077

Polymorphism and mutation databases

DMDMi46577654

Proteomic databases

EPDiP61077
MaxQBiP61077
PeptideAtlasiP61077
PRIDEiP61077
ProteomicsDBi57258
57259 [P61077-2]
57260 [P61077-3]
TopDownProteomicsiP61077-1 [P61077-1]
P61077-2 [P61077-2]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000321805; ENSP00000318494; ENSG00000109332 [P61077-1]
ENST00000338145; ENSP00000337208; ENSG00000109332 [P61077-1]
ENST00000343106; ENSP00000345285; ENSG00000109332 [P61077-2]
ENST00000349311; ENSP00000344069; ENSG00000109332 [P61077-1]
ENST00000357194; ENSP00000349722; ENSG00000109332 [P61077-3]
ENST00000394801; ENSP00000378280; ENSG00000109332 [P61077-1]
ENST00000394803; ENSP00000378282; ENSG00000109332 [P61077-1]
ENST00000394804; ENSP00000378283; ENSG00000109332 [P61077-1]
ENST00000453744; ENSP00000396901; ENSG00000109332 [P61077-1]
GeneIDi7323
KEGGihsa:7323
UCSCiuc003hwi.5 human [P61077-1]

Organism-specific databases

CTDi7323
DisGeNETi7323
EuPathDBiHostDB:ENSG00000109332.19
GeneCardsiUBE2D3
HGNCiHGNC:12476 UBE2D3
HPAiHPA003920
MIMi602963 gene
neXtProtiNX_P61077
OpenTargetsiENSG00000109332
PharmGKBiPA37126
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0417 Eukaryota
COG5078 LUCA
GeneTreeiENSGT00910000143990
HOVERGENiHBG063308
InParanoidiP61077
KOiK06689
OMAiDVYHWQA
OrthoDBiEOG091G0GF8
PhylomeDBiP61077
TreeFamiTF101108

Enzyme and pathway databases

UniPathwayi
UPA00143

BRENDAi2.3.2.B6 2681
ReactomeiR-HSA-1234176 Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha
R-HSA-168927 TICAM1, RIP1-mediated IKK complex recruitment
R-HSA-201451 Signaling by BMP
R-HSA-2173795 Downregulation of SMAD2/3:SMAD4 transcriptional activity
R-HSA-8866654 E3 ubiquitin ligases ubiquitinate target proteins
R-HSA-8951664 Neddylation
R-HSA-9033241 Peroxisomal protein import
R-HSA-936440 Negative regulators of DDX58/IFIH1 signaling
R-HSA-937041 IKK complex recruitment mediated by RIP1
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
SignaLinkiP61077
SIGNORiP61077

Miscellaneous databases

ChiTaRSiUBE2D3 human
EvolutionaryTraceiP61077
GeneWikiiUBE2D3
GenomeRNAii7323
PROiPR:P61077
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000109332 Expressed in 234 organ(s), highest expression level in secondary oocyte
CleanExiHS_UBE2D3
ExpressionAtlasiP61077 baseline and differential
GenevisibleiP61077 HS

Family and domain databases

CDDicd00195 UBCc, 1 hit
Gene3Di3.10.110.10, 1 hit
InterProiView protein in InterPro
IPR000608 UBQ-conjugat_E2
IPR023313 UBQ-conjugating_AS
IPR016135 UBQ-conjugating_enzyme/RWD
PfamiView protein in Pfam
PF00179 UQ_con, 1 hit
SUPFAMiSSF54495 SSF54495, 1 hit
PROSITEiView protein in PROSITE
PS00183 UBIQUITIN_CONJUGAT_1, 1 hit
PS50127 UBIQUITIN_CONJUGAT_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiUB2D3_HUMAN
AccessioniPrimary (citable) accession number: P61077
Secondary accession number(s): A6NJ93
, A6NJB1, A6NM99, P47986, Q6IB88, Q6NXS4, Q8N924
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 26, 2004
Last sequence update: April 26, 2004
Last modified: November 7, 2018
This is version 162 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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