UniProtKB - P61081 (UBC12_HUMAN)
Protein
NEDD8-conjugating enzyme Ubc12
Gene
UBE2M
Organism
Homo sapiens (Human)
Status
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
- [E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine + [E2 NEDD8-conjugating enzyme]-L-cysteine = [E1 NEDD8-activating enzyme]-L-cysteine + [E2 NEDD8-conjugating enzyme]-S-[NEDD8-protein]-yl-L-cysteine.1 Publication EC:2.3.2.34
: protein neddylation Pathwayi
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 111 | Glycyl thioester intermediatePROSITE-ProRule annotation | 1 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- NEDD8 transferase activity Source: UniProtKB
- ubiquitin conjugating enzyme activity Source: GO_Central
- 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
- protein polyubiquitination Source: GO_Central
Keywordsi
Molecular function | Transferase |
Biological process | Ubl conjugation pathway |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
BioCyci | MetaCyc:HS05432-MONOMER |
PathwayCommonsi | P61081 |
Reactomei | R-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 |
SignaLinki | P61081 |
UniPathwayi | UPA00885 |
Names & Taxonomyi
Protein namesi | Recommended name: NEDD8-conjugating enzyme Ubc12 (EC:2.3.2.341 Publication)Alternative name(s): NEDD8 carrier protein Ubiquitin-conjugating enzyme E2 M |
Gene namesi | Name:UBE2M Synonyms:UBC12 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000130725.7 |
HGNCi | HGNC:12491, UBE2M |
MIMi | 603173, gene |
neXtProti | NX_P61081 |
Subcellular locationi
Cytosol
- cytosol Source: Reactome
Nucleus
- nucleoplasm Source: Reactome
- nucleus Source: GO_Central
Pathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 1 | M → A: No effect on thioester intermediate formation. 1 Publication | 1 | |
Mutagenesisi | 4 | L → A: Impairs thioester intermediate formation. 1 Publication | 1 | |
Mutagenesisi | 5 | F → A: Strongly impairs thioester intermediate formation. 1 Publication | 1 | |
Mutagenesisi | 6 | S → A: Slightly impairs thioester intermediate formation. 1 Publication | 1 | |
Mutagenesisi | 7 | L → A: Strongly impairs thioester intermediate formation. 1 Publication | 1 | |
Mutagenesisi | 9 | Q → A: Impairs thioester intermediate formation. 1 Publication | 1 | |
Mutagenesisi | 10 | Q → A: No effect on thioester intermediate formation. 1 Publication | 1 | |
Mutagenesisi | 11 | K → A: No effect on thioester intermediate formation. 1 Publication | 1 | |
Mutagenesisi | 12 | K → A: Impairs thioester intermediate formation. 1 Publication | 1 | |
Mutagenesisi | 32 | L → A: Strongly impairs thioester intermediate formation. 1 Publication | 1 | |
Mutagenesisi | 35 | Q → A: Strongly impairs thioester intermediate formation. 1 Publication | 1 | |
Mutagenesisi | 36 | K → A: Strongly impairs thioester intermediate formation. 1 Publication | 1 | |
Mutagenesisi | 38 | I → A: Strongly impairs thioester intermediate formation. 1 Publication | 1 | |
Mutagenesisi | 39 | N → A: No effect on thioester intermediate formation. 1 Publication | 1 | |
Mutagenesisi | 41 | L → A: Strongly impairs thioester intermediate formation. 1 Publication | 1 | |
Mutagenesisi | 51 | F → A: Strongly impairs thioester intermediate formation. 1 Publication | 1 | |
Mutagenesisi | 55 | D → A: Strongly impairs thioester intermediate formation. 1 Publication | 1 | |
Mutagenesisi | 57 | L → A: Strongly impairs thioester intermediate formation. 1 Publication | 1 | |
Mutagenesisi | 111 | C → S: Forms a stable complex with NEDD8, which prevents subsequent NEDD8 conjugation to cullins. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 9040 |
OpenTargetsi | ENSG00000130725 |
PharmGKBi | PA37140 |
Miscellaneous databases
Pharosi | P61081, Tbio |
Chemistry databases
ChEMBLi | CHEMBL4295787 |
Polymorphism and mutation databases
BioMutai | UBE2M |
DMDMi | 46577655 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000082488 | 1 – 183 | NEDD8-conjugating enzyme Ubc12Add BLAST | 183 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 1 | N-acetylmethionine2 Publications | 1 | |
Modified residuei | 3 | N6-acetyllysineCombined sources | 1 | |
Modified residuei | 50 | PhosphoserineCombined sources | 1 | |
Modified residuei | 169 | Asymmetric dimethylarginine; alternateBy similarity | 1 | |
Modified residuei | 169 | Omega-N-methylarginine; alternateCombined sources | 1 |
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, PhosphoproteinProteomic databases
EPDi | P61081 |
jPOSTi | P61081 |
MassIVEi | P61081 |
MaxQBi | P61081 |
PaxDbi | P61081 |
PeptideAtlasi | P61081 |
PRIDEi | P61081 |
ProteomicsDBi | 57261 |
2D gel databases
REPRODUCTION-2DPAGEi | IPI00022597 |
UCD-2DPAGEi | P61081 |
PTM databases
iPTMneti | P61081 |
PhosphoSitePlusi | P61081 |
SwissPalmi | P61081 |
Expressioni
Gene expression databases
Bgeei | ENSG00000130725, Expressed in superior frontal gyrus and 221 other tissues |
ExpressionAtlasi | P61081, baseline and differential |
Genevisiblei | P61081, HS |
Organism-specific databases
HPAi | ENSG00000130725, Low tissue specificity |
Interactioni
Subunit structurei
Binary interactionsi
Hide detailsP61081
With | #Exp. | IntAct |
---|---|---|
CUL1 [Q13616] | 5 | EBI-1041660,EBI-359390 |
DCUN1D1 [Q96GG9] | 4 | EBI-1041660,EBI-740086 |
NEDD8 [Q15843] | 8 | EBI-1041660,EBI-716247 |
RBX1 [P62877] | 7 | EBI-1041660,EBI-398523 |
UBA3 [Q8TBC4] | 2 | EBI-1041660,EBI-717567 |
Protein-protein interaction databases
BioGRIDi | 114504, 588 interactors |
DIPi | DIP-35679N |
IntActi | P61081, 45 interactors |
MINTi | P61081 |
STRINGi | 9606.ENSP00000253023 |
Miscellaneous databases
RNActi | P61081, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | P61081 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P61081 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 29 – 173 | UBC corePROSITE-ProRule annotationAdd BLAST | 145 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 57 | Interaction with UBA3Add BLAST | 57 |
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
Phylogenomic databases
eggNOGi | KOG0420, Eukaryota |
GeneTreei | ENSGT00940000162814 |
HOGENOMi | CLU_030988_6_0_1 |
InParanoidi | P61081 |
OMAi | NTNYPHE |
OrthoDBi | 1302735at2759 |
PhylomeDBi | P61081 |
TreeFami | TF101125 |
Family and domain databases
CDDi | cd00195, UBCc, 1 hit |
Gene3Di | 3.10.110.10, 1 hit |
InterProi | View protein in InterPro IPR000608, UBQ-conjugat_E2 IPR023313, UBQ-conjugating_AS IPR016135, UBQ-conjugating_enzyme/RWD |
Pfami | View protein in Pfam PF00179, UQ_con, 1 hit |
SUPFAMi | SSF54495, SSF54495, 1 hit |
PROSITEi | View protein in PROSITE PS00183, UBC_1, 1 hit PS50127, UBC_2, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All
P61081-1 [UniParc]FASTAAdd to basket
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
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketM0QYI6 | M0QYI6_HUMAN | NEDD8-conjugating enzyme Ubc12 | UBE2M | 114 | Annotation score: | ||
M0QX69 | M0QX69_HUMAN | NEDD8-conjugating enzyme Ubc12 | UBE2M | 69 | Annotation score: |
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 |
CCDSi | CCDS12987.1 |
RefSeqi | NP_003960.1, NM_003969.3 |
Genome annotation databases
Ensembli | ENST00000253023; ENSP00000253023; ENSG00000130725 |
GeneIDi | 9040 |
KEGGi | hsa:9040 |
UCSCi | uc002qtl.5, human |
Similar proteinsi
Cross-referencesi
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 |
CCDSi | CCDS12987.1 |
RefSeqi | NP_003960.1, NM_003969.3 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1TT5 | X-ray | 2.60 | E/F | 1-26 | [»] | |
1Y8X | X-ray | 2.40 | A | 27-183 | [»] | |
2NVU | X-ray | 2.80 | C | 1-178 | [»] | |
3TDU | X-ray | 1.50 | E/F | 1-15 | [»] | |
3TDZ | X-ray | 2.00 | E/F | 2-12 | [»] | |
4GAO | X-ray | 3.28 | C/E/F/H | 1-12 | [»] | |
4P5O | X-ray | 3.11 | G/I | 2-183 | [»] | |
SMRi | P61081 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 114504, 588 interactors |
DIPi | DIP-35679N |
IntActi | P61081, 45 interactors |
MINTi | P61081 |
STRINGi | 9606.ENSP00000253023 |
Chemistry databases
ChEMBLi | CHEMBL4295787 |
PTM databases
iPTMneti | P61081 |
PhosphoSitePlusi | P61081 |
SwissPalmi | P61081 |
Polymorphism and mutation databases
BioMutai | UBE2M |
DMDMi | 46577655 |
2D gel databases
REPRODUCTION-2DPAGEi | IPI00022597 |
UCD-2DPAGEi | P61081 |
Proteomic databases
EPDi | P61081 |
jPOSTi | P61081 |
MassIVEi | P61081 |
MaxQBi | P61081 |
PaxDbi | P61081 |
PeptideAtlasi | P61081 |
PRIDEi | P61081 |
ProteomicsDBi | 57261 |
Protocols and materials databases
Antibodypediai | 3333, 191 antibodies |
DNASUi | 9040 |
Genome annotation databases
Ensembli | ENST00000253023; ENSP00000253023; ENSG00000130725 |
GeneIDi | 9040 |
KEGGi | hsa:9040 |
UCSCi | uc002qtl.5, human |
Organism-specific databases
CTDi | 9040 |
DisGeNETi | 9040 |
EuPathDBi | HostDB:ENSG00000130725.7 |
GeneCardsi | UBE2M |
HGNCi | HGNC:12491, UBE2M |
HPAi | ENSG00000130725, Low tissue specificity |
MIMi | 603173, gene |
neXtProti | NX_P61081 |
OpenTargetsi | ENSG00000130725 |
PharmGKBi | PA37140 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0420, Eukaryota |
GeneTreei | ENSGT00940000162814 |
HOGENOMi | CLU_030988_6_0_1 |
InParanoidi | P61081 |
OMAi | NTNYPHE |
OrthoDBi | 1302735at2759 |
PhylomeDBi | P61081 |
TreeFami | TF101125 |
Enzyme and pathway databases
UniPathwayi | UPA00885 |
BioCyci | MetaCyc:HS05432-MONOMER |
PathwayCommonsi | P61081 |
Reactomei | R-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 |
SignaLinki | P61081 |
Miscellaneous databases
BioGRID-ORCSi | 9040, 674 hits in 827 CRISPR screens |
ChiTaRSi | UBE2M, human |
EvolutionaryTracei | P61081 |
GeneWikii | UBE2M |
GenomeRNAii | 9040 |
Pharosi | P61081, Tbio |
PROi | PR:P61081 |
RNActi | P61081, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000130725, Expressed in superior frontal gyrus and 221 other tissues |
ExpressionAtlasi | P61081, baseline and differential |
Genevisiblei | P61081, HS |
Family and domain databases
CDDi | cd00195, UBCc, 1 hit |
Gene3Di | 3.10.110.10, 1 hit |
InterProi | View protein in InterPro IPR000608, UBQ-conjugat_E2 IPR023313, UBQ-conjugating_AS IPR016135, UBQ-conjugating_enzyme/RWD |
Pfami | View protein in Pfam PF00179, UQ_con, 1 hit |
SUPFAMi | SSF54495, SSF54495, 1 hit |
PROSITEi | View protein in PROSITE PS00183, UBC_1, 1 hit PS50127, UBC_2, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | UBC12_HUMAN | |
Accessioni | P61081Primary (citable) accession number: P61081 Secondary accession number(s): O76069, Q8VC50 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 26, 2004 |
Last sequence update: | April 26, 2004 | |
Last modified: | December 2, 2020 | |
This is version 170 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Reference proteomeDocuments
- MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human chromosome 19
Human chromosome 19: entries, gene names and cross-references to MIM