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Protein

NEDD8-conjugating enzyme Ubc12

Gene

UBE2M

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

Functioni

Accepts the ubiquitin-like protein NEDD8 from the UBA3-NAE1 E1 complex and catalyzes its covalent attachment to other proteins. The specific interaction with the E3 ubiquitin ligase RBX1, but not RBX2, suggests that the RBX1-UBE2M complex neddylates specific target proteins, such as CUL1, CUL2, CUL3 and CUL4. Involved in cell proliferation.2 Publications

Catalytic activityi

ATP + NEDD8 + protein lysine = AMP + diphosphate + protein N-NEDD8yllysine.

Pathwayi: protein neddylation

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei111Glycyl thioester intermediate1

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • NEDD8 transferase activity Source: UniProtKB
  • ubiquitin-protein transferase activity Source: UniProtKB

GO - Biological processi

  • cellular protein modification process Source: UniProtKB
  • positive regulation of neuron apoptotic process Source: Ensembl
  • post-translational protein modification Source: Reactome
  • protein neddylation Source: UniProtKB

Keywordsi

Molecular functionTransferase
Biological processUbl conjugation pathway
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS05432-MONOMER
ReactomeiR-HSA-2173789 TGF-beta receptor signaling activates SMADs
R-HSA-5607761 Dectin-1 mediated noncanonical NF-kB signaling
R-HSA-5676590 NIK-->noncanonical NF-kB signaling
R-HSA-8951664 Neddylation
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
SignaLinkiP61081
UniPathwayiUPA00885

Names & Taxonomyi

Protein namesi
Recommended name:
NEDD8-conjugating enzyme Ubc12 (EC:2.3.2.-)
Alternative name(s):
NEDD8 carrier protein
Ubiquitin-conjugating enzyme E2 M
Gene namesi
Name:UBE2M
Synonyms:UBC12
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000130725.7
HGNCiHGNC:12491 UBE2M
MIMi603173 gene
neXtProtiNX_P61081

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi1M → A: No effect on thioester intermediate formation. 1 Publication1
Mutagenesisi4L → A: Impairs thioester intermediate formation. 1 Publication1
Mutagenesisi5F → A: Strongly impairs thioester intermediate formation. 1 Publication1
Mutagenesisi6S → A: Slightly impairs thioester intermediate formation. 1 Publication1
Mutagenesisi7L → A: Strongly impairs thioester intermediate formation. 1 Publication1
Mutagenesisi9Q → A: Impairs thioester intermediate formation. 1 Publication1
Mutagenesisi10Q → A: No effect on thioester intermediate formation. 1 Publication1
Mutagenesisi11K → A: No effect on thioester intermediate formation. 1 Publication1
Mutagenesisi12K → A: Impairs thioester intermediate formation. 1 Publication1
Mutagenesisi32L → A: Strongly impairs thioester intermediate formation. 1 Publication1
Mutagenesisi35Q → A: Strongly impairs thioester intermediate formation. 1 Publication1
Mutagenesisi36K → A: Strongly impairs thioester intermediate formation. 1 Publication1
Mutagenesisi38I → A: Strongly impairs thioester intermediate formation. 1 Publication1
Mutagenesisi39N → A: No effect on thioester intermediate formation. 1 Publication1
Mutagenesisi41L → A: Strongly impairs thioester intermediate formation. 1 Publication1
Mutagenesisi51F → A: Strongly impairs thioester intermediate formation. 1 Publication1
Mutagenesisi55D → A: Strongly impairs thioester intermediate formation. 1 Publication1
Mutagenesisi57L → A: Strongly impairs thioester intermediate formation. 1 Publication1
Mutagenesisi111C → S: Forms a stable complex with NEDD8, which prevents subsequent NEDD8 conjugation to cullins. 1 Publication1

Organism-specific databases

DisGeNETi9040
OpenTargetsiENSG00000130725
PharmGKBiPA37140

Polymorphism and mutation databases

BioMutaiUBE2M
DMDMi46577655

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000824881 – 183NEDD8-conjugating enzyme Ubc12Add BLAST183

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionine2 Publications1
Modified residuei3N6-acetyllysineCombined sources1
Modified residuei50PhosphoserineCombined sources1
Modified residuei169Asymmetric dimethylarginine; alternateBy similarity1
Modified residuei169Omega-N-methylarginine; alternateCombined sources1

Post-translational modificationi

The acetylation of Met-1 increases affinity for DCUN1D1 by about 2 orders of magnitude and is crucial for NEDD8 transfer to cullins.2 Publications

Keywords - PTMi

Acetylation, Methylation, Phosphoprotein

Proteomic databases

EPDiP61081
MaxQBiP61081
PaxDbiP61081
PeptideAtlasiP61081
PRIDEiP61081

2D gel databases

REPRODUCTION-2DPAGEIPI00022597
UCD-2DPAGEP61081

PTM databases

iPTMnetiP61081
PhosphoSitePlusiP61081
SwissPalmiP61081

Expressioni

Gene expression databases

BgeeiENSG00000130725
CleanExiHS_UBE2M
ExpressionAtlasiP61081 baseline and differential
GenevisibleiP61081 HS

Organism-specific databases

HPAiCAB004993
HPA054551
HPA057800

Interactioni

Subunit structurei

Interacts with UBA3 and RBX1. Interacts (acetylated at N-terminal methionine) with DCUN1D1 (via DCUN1 domain) (PubMed:28581483).6 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi114504, 88 interactors
DIPiDIP-35679N
IntActiP61081, 21 interactors
MINTiP61081
STRINGi9606.ENSP00000253023

Structurei

Secondary structure

1183
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi4 – 14Combined sources11
Helixi29 – 39Combined sources11
Beta strandi47 – 50Combined sources4
Beta strandi59 – 64Combined sources6
Beta strandi67 – 69Combined sources3
Turni70 – 73Combined sources4
Beta strandi76 – 81Combined sources6
Turni84 – 88Combined sources5
Beta strandi92 – 95Combined sources4
Beta strandi108 – 110Combined sources3
Helixi113 – 115Combined sources3
Turni116 – 118Combined sources3
Helixi125 – 137Combined sources13
Helixi147 – 154Combined sources8
Helixi157 – 169Combined sources13
Beta strandi170 – 173Combined sources4
Beta strandi176 – 178Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1TT5X-ray2.60E/F1-26[»]
1Y8XX-ray2.40A27-183[»]
2NVUX-ray2.80C1-178[»]
3TDUX-ray1.50E/F1-15[»]
3TDZX-ray2.00E/F2-12[»]
4GAOX-ray3.28C/E/F/H1-12[»]
4P5OX-ray3.11G/I2-183[»]
ProteinModelPortaliP61081
SMRiP61081
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP61081

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 57Interaction with UBA3Add BLAST57

Domaini

Both the N-terminal docking peptide and the catalytic core domain must bind the UBA3-NAE1 complex simultaneously for optimal transfer of NEDD8.

Sequence similaritiesi

Belongs to the ubiquitin-conjugating enzyme family. UBC12 subfamily.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0420 Eukaryota
ENOG410XS81 LUCA
GeneTreeiENSGT00630000089859
HOGENOMiHOG000233456
HOVERGENiHBG098591
InParanoidiP61081
KOiK10579
OMAiMIKIWSM
OrthoDBiEOG091G0N8A
PhylomeDBiP61081
TreeFamiTF101125

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

Sequencei

Sequence statusi: Complete.

P61081-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MIKLFSLKQQ KKEEESAGGT KGSSKKASAA QLRIQKDINE LNLPKTCDIS
60 70 80 90 100
FSDPDDLLNF KLVICPDEGF YKSGKFVFSF KVGQGYPHDP PKVKCETMVY
110 120 130 140 150
HPNIDLEGNV CLNILREDWK PVLTINSIIY GLQYLFLEPN PEDPLNKEAA
160 170 180
EVLQNNRRLF EQNVQRSMRG GYIGSTYFER CLK
Length:183
Mass (Da):20,900
Last modified:April 26, 2004 - v1
Checksum:iE3C288CA6A98BC5C
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB012191 mRNA Translation: BAA33145.1
AF075599 mRNA Translation: AAC26141.1
BT006754 mRNA Translation: AAP35400.1
BC058924 mRNA Translation: AAH58924.1
CCDSiCCDS12987.1
RefSeqiNP_003960.1, NM_003969.3
UniGeneiHs.406068

Genome annotation databases

EnsembliENST00000253023; ENSP00000253023; ENSG00000130725
GeneIDi9040
KEGGihsa:9040
UCSCiuc002qtl.5 human

Similar proteinsi

Entry informationi

Entry nameiUBC12_HUMAN
AccessioniPrimary (citable) accession number: P61081
Secondary accession number(s): O76069, Q8VC50
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 26, 2004
Last sequence update: April 26, 2004
Last modified: May 23, 2018
This is version 150 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

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