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Protein

NEDD8-conjugating enzyme Ubc12

Gene

UBE2M

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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)LengthDescriptionGraphical viewFeature identifierActions
Active sitei111 – 1111Glycyl thioester intermediate

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • NEDD8 transferase activity Source: UniProtKB
  • ribosomal S6-glutamic acid ligase activity Source: UniProtKB
  • ubiquitin-protein transferase activity Source: UniProtKB

GO - Biological processi

  • cellular protein modification process Source: UniProtKB
  • NIK/NF-kappaB signaling Source: Reactome
  • positive regulation of neuron apoptotic process Source: Ensembl
  • protein neddylation Source: UniProtKB
  • transforming growth factor beta receptor signaling pathway Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Ubl conjugation pathway

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

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-983168. Antigen processing: Ubiquitination & Proteasome degradation.
SignaLinkiP61081.
UniPathwayiUPA00885.

Names & Taxonomyi

Protein namesi
Recommended name:
NEDD8-conjugating enzyme Ubc12 (EC:6.3.2.-)
Alternative name(s):
NEDD8 carrier protein
NEDD8 protein ligase
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

HGNCiHGNC:12491. UBE2M.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: GO_Central
  • cytosol Source: Reactome
  • extracellular exosome Source: UniProtKB
Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi1 – 11M → A: No effect on thioester intermediate formation. 1 Publication
Mutagenesisi4 – 41L → A: Impairs thioester intermediate formation. 1 Publication
Mutagenesisi5 – 51F → A: Strongly impairs thioester intermediate formation. 1 Publication
Mutagenesisi6 – 61S → A: Slightly impairs thioester intermediate formation. 1 Publication
Mutagenesisi7 – 71L → A: Strongly impairs thioester intermediate formation. 1 Publication
Mutagenesisi9 – 91Q → A: Impairs thioester intermediate formation. 1 Publication
Mutagenesisi10 – 101Q → A: No effect on thioester intermediate formation. 1 Publication
Mutagenesisi11 – 111K → A: No effect on thioester intermediate formation. 1 Publication
Mutagenesisi12 – 121K → A: Impairs thioester intermediate formation. 1 Publication
Mutagenesisi32 – 321L → A: Strongly impairs thioester intermediate formation. 1 Publication
Mutagenesisi35 – 351Q → A: Strongly impairs thioester intermediate formation. 1 Publication
Mutagenesisi36 – 361K → A: Strongly impairs thioester intermediate formation. 1 Publication
Mutagenesisi38 – 381I → A: Strongly impairs thioester intermediate formation. 1 Publication
Mutagenesisi39 – 391N → A: No effect on thioester intermediate formation. 1 Publication
Mutagenesisi41 – 411L → A: Strongly impairs thioester intermediate formation. 1 Publication
Mutagenesisi51 – 511F → A: Strongly impairs thioester intermediate formation. 1 Publication
Mutagenesisi55 – 551D → A: Strongly impairs thioester intermediate formation. 1 Publication
Mutagenesisi57 – 571L → A: Strongly impairs thioester intermediate formation. 1 Publication
Mutagenesisi111 – 1111C → S: Forms a stable complex with NEDD8, which prevents subsequent NEDD8 conjugation to cullins. 1 Publication

Organism-specific databases

PharmGKBiPA37140.

Polymorphism and mutation databases

BioMutaiUBE2M.
DMDMi46577655.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 183183NEDD8-conjugating enzyme Ubc12PRO_0000082488Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionine2 Publications
Modified residuei3 – 31N6-acetyllysineCombined sources
Modified residuei50 – 501PhosphoserineCombined sources

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, Phosphoprotein

Proteomic databases

EPDiP61081.
MaxQBiP61081.
PaxDbiP61081.
PeptideAtlasiP61081.
PRIDEiP61081.

2D gel databases

REPRODUCTION-2DPAGEIPI00022597.
UCD-2DPAGEP61081.

PTM databases

iPTMnetiP61081.
PhosphoSiteiP61081.
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, DCUN1D1 and RBX1.5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CUL1Q136165EBI-1041660,EBI-359390
NEDD8Q158433EBI-1041660,EBI-716247
UBA3Q8TBC42EBI-1041660,EBI-717567

Protein-protein interaction databases

BioGridi114504. 81 interactions.
DIPiDIP-35679N.
IntActiP61081. 17 interactions.
MINTiMINT-5002641.
STRINGi9606.ENSP00000253023.

Structurei

Secondary structure

1
183
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi4 – 1411Combined sources
Helixi29 – 3911Combined sources
Beta strandi47 – 504Combined sources
Beta strandi59 – 646Combined sources
Beta strandi67 – 693Combined sources
Turni70 – 734Combined sources
Beta strandi76 – 816Combined sources
Turni84 – 885Combined sources
Beta strandi92 – 954Combined sources
Beta strandi108 – 1103Combined sources
Helixi113 – 1153Combined sources
Turni116 – 1183Combined sources
Helixi125 – 13713Combined sources
Helixi147 – 1548Combined sources
Helixi157 – 16913Combined sources
Beta strandi170 – 1734Combined sources
Beta strandi176 – 1783Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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. Positions 27-183.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP61081.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 5757Interaction with UBA3Add
BLAST

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.
OMAiHEPPKVR.
OrthoDBiEOG091G0N8A.
PhylomeDBiP61081.
TreeFamiTF101125.

Family and domain databases

Gene3Di3.10.110.10. 1 hit.
InterProiIPR000608. UBQ-conjugat_E2.
IPR023313. UBQ-conjugating_AS.
IPR016135. UBQ-conjugating_enzyme/RWD.
[Graphical view]
PfamiPF00179. UQ_con. 1 hit.
[Graphical view]
SUPFAMiSSF54495. SSF54495. 1 hit.
PROSITEiPS00183. UBIQUITIN_CONJUGAT_1. 1 hit.
PS50127. UBIQUITIN_CONJUGAT_2. 1 hit.
[Graphical view]

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.

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.
CCDSiCCDS12987.1.
RefSeqiNP_003960.1. NM_003969.3.
UniGeneiHs.406068.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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. Positions 27-183.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114504. 81 interactions.
DIPiDIP-35679N.
IntActiP61081. 17 interactions.
MINTiMINT-5002641.
STRINGi9606.ENSP00000253023.

PTM databases

iPTMnetiP61081.
PhosphoSiteiP61081.
SwissPalmiP61081.

Polymorphism and mutation databases

BioMutaiUBE2M.
DMDMi46577655.

2D gel databases

REPRODUCTION-2DPAGEIPI00022597.
UCD-2DPAGEP61081.

Proteomic databases

EPDiP61081.
MaxQBiP61081.
PaxDbiP61081.
PeptideAtlasiP61081.
PRIDEiP61081.

Protocols and materials databases

DNASUi9040.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi9040.
GeneCardsiUBE2M.
HGNCiHGNC:12491. UBE2M.
HPAiCAB004993.
HPA054551.
HPA057800.
MIMi603173. gene.
neXtProtiNX_P61081.
PharmGKBiPA37140.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

UniPathwayiUPA00885.
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-983168. Antigen processing: Ubiquitination & Proteasome degradation.
SignaLinkiP61081.

Miscellaneous databases

ChiTaRSiUBE2M. human.
EvolutionaryTraceiP61081.
GeneWikiiUBE2M.
GenomeRNAii9040.
PROiP61081.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000130725.
CleanExiHS_UBE2M.
ExpressionAtlasiP61081. baseline and differential.
GenevisibleiP61081. HS.

Family and domain databases

Gene3Di3.10.110.10. 1 hit.
InterProiIPR000608. UBQ-conjugat_E2.
IPR023313. UBQ-conjugating_AS.
IPR016135. UBQ-conjugating_enzyme/RWD.
[Graphical view]
PfamiPF00179. UQ_con. 1 hit.
[Graphical view]
SUPFAMiSSF54495. SSF54495. 1 hit.
PROSITEiPS00183. UBIQUITIN_CONJUGAT_1. 1 hit.
PS50127. UBIQUITIN_CONJUGAT_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiUBC12_HUMAN
AccessioniPrimary (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: September 7, 2016
This is version 136 of the entry and version 1 of the sequence. [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. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.