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P61081 (UBC12_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 113. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
NEDD8-conjugating enzyme Ubc12

EC=6.3.2.-
Alternative name(s):
NEDD8 carrier protein
NEDD8 protein ligase
Ubiquitin-conjugating enzyme E2 M
Gene names
Name:UBE2M
Synonyms:UBC12
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length183 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.2 Ref.10

Catalytic activity

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

Pathway

Protein modification; protein neddylation.

Subunit structure

Interacts with UBA3, DCUN1D1 and RBX1. Ref.7

Domain

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

Post-translational modification

The acetylation of Met-1 increases affinity for DCUN1D1 by about 2 orders of magnitude and is crucial for NEDD8 transfer to cullins. Ref.12 Ref.13

Sequence similarities

Belongs to the ubiquitin-conjugating enzyme family. UBC12 subfamily.

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 183183NEDD8-conjugating enzyme Ubc12
PRO_0000082488

Regions

Region1 – 2626Interaction with UBA3
Region27 – 5731Interaction with UBA3

Sites

Active site1111Glycyl thioester intermediate

Amino acid modifications

Modified residue11N-acetylmethionine Ref.8 Ref.12 Ref.13
Modified residue31N6-acetyllysine Ref.8
Modified residue501Phosphoserine Ref.6

Experimental info

Mutagenesis11M → A: No effect on thioester intermediate formation. Ref.10
Mutagenesis41L → A: Impairs thioester intermediate formation. Ref.10
Mutagenesis51F → A: Strongly impairs thioester intermediate formation. Ref.10
Mutagenesis61S → A: Slightly impairs thioester intermediate formation. Ref.10
Mutagenesis71L → A: Strongly impairs thioester intermediate formation. Ref.10
Mutagenesis91Q → A: Impairs thioester intermediate formation. Ref.10
Mutagenesis101Q → A: No effect on thioester intermediate formation. Ref.10
Mutagenesis111K → A: No effect on thioester intermediate formation. Ref.10
Mutagenesis121K → A: Impairs thioester intermediate formation. Ref.10
Mutagenesis321L → A: Strongly impairs thioester intermediate formation. Ref.11
Mutagenesis351Q → A: Strongly impairs thioester intermediate formation. Ref.11
Mutagenesis361K → A: Strongly impairs thioester intermediate formation. Ref.11
Mutagenesis381I → A: Strongly impairs thioester intermediate formation. Ref.11
Mutagenesis391N → A: No effect on thioester intermediate formation. Ref.11
Mutagenesis411L → A: Strongly impairs thioester intermediate formation. Ref.11
Mutagenesis511F → A: Strongly impairs thioester intermediate formation. Ref.11
Mutagenesis551D → A: Strongly impairs thioester intermediate formation. Ref.11
Mutagenesis571L → A: Strongly impairs thioester intermediate formation. Ref.11
Mutagenesis1111C → S: Forms a stable complex with NEDD8, which prevents subsequent NEDD8 conjugation to cullins. Ref.5

Secondary structure

................................ 183
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P61081 [UniParc].

Last modified April 26, 2004. Version 1.
Checksum: E3C288CA6A98BC5C

FASTA18320,900
        10         20         30         40         50         60 
MIKLFSLKQQ KKEEESAGGT KGSSKKASAA QLRIQKDINE LNLPKTCDIS FSDPDDLLNF 

        70         80         90        100        110        120 
KLVICPDEGF YKSGKFVFSF KVGQGYPHDP PKVKCETMVY HPNIDLEGNV CLNILREDWK 

       130        140        150        160        170        180 
PVLTINSIIY GLQYLFLEPN PEDPLNKEAA EVLQNNRRLF EQNVQRSMRG GYIGSTYFER 


CLK 

« Hide

References

« Hide 'large scale' references
[1]"A new NEDD8-ligating system for cullin-4A."
Osaka F., Kawasaki H., Aida N., Saeki M., Chiba T., Kawashima S., Tanaka K., Kato S.
Genes Dev. 12:2263-2268(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Identification of the activating and conjugating enzymes of the NEDD8 conjugation pathway."
Gong L., Yeh E.T.H.
J. Biol. Chem. 274:12036-12042(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION.
Tissue: Placenta.
[3]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Skin.
[5]"A dominant-negative UBC12 mutant sequesters NEDD8 and inhibits NEDD8 conjugation in vivo."
Wada H., Yeh E.T.H., Kamitani T.
J. Biol. Chem. 275:17008-17015(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF CYS-111.
[6]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-50, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[7]"E2-RING expansion of the NEDD8 cascade confers specificity to cullin modification."
Huang D.T., Ayrault O., Hunt H.W., Taherbhoy A.M., Duda D.M., Scott D.C., Borg L.A., Neale G., Murray P.J., Roussel M.F., Schulman B.A.
Mol. Cell 33:483-495(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RBX1.
[8]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 AND LYS-3, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"A unique E1-E2 interaction required for optimal conjugation of the ubiquitin-like protein NEDD8."
Huang D.T., Miller D.W., Mathew R., Cassell R., Holton J.M., Roussel M.F., Schulman B.A.
Nat. Struct. Mol. Biol. 11:927-935(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 1-26 IN COMPLEX WITH UBA3 AND NAE1, MUTAGENESIS OF MET-1; LEU-4; PHE-5; SER-6; LEU-7; GLN-9; GLN-10; LYS-11 AND LYS-12, FUNCTION.
[11]"Structural basis for recruitment of Ubc12 by an E2 binding domain in NEDD8's E1."
Huang D.T., Paydar A., Zhuang M., Waddell M.B., Holton J.M., Schulman B.A.
Mol. Cell 17:341-350(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 27-183 IN COMPLEX WITH UBA3 AND NAE1, MUTAGENESIS OF LEU-32; GLN-35; LYS-36; ILE-38; ASN-39; LEU-41; PHE-51; ASP-55 AND LEU-57.
[12]"N-terminal acetylation acts as an avidity enhancer within an interconnected multiprotein complex."
Scott D.C., Monda J.K., Bennett E.J., Harper J.W., Schulman B.A.
Science 334:674-678(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 2-15 IN COMPLEX WITH CUL1 AND DCUN1D1, X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1-12 IN COMPLEX WITH CUL1 AND DCUN1D1, ACETYLATION AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY.
[13]"Structural conservation of distinctive N-terminal acetylation-dependent interactions across a family of mammalian NEDD8 ligation enzymes."
Monda J.K., Scott D.C., Miller D.J., Lydeard J., King D., Harper J.W., Bennett E.J., Schulman B.A.
Structure 21:42-53(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.28 ANGSTROMS) OF 1-12 IN COMPLEX WITH DCUN1D2, ACETYLATION AT MET-1.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB012191 mRNA. Translation: BAA33145.1.
AF075599 mRNA. Translation: AAC26141.1.
BT006754 mRNA. Translation: AAP35400.1.
BC058924 mRNA. Translation: AAH58924.1.
CCDSCCDS12987.1.
RefSeqNP_003960.1. NM_003969.3.
UniGeneHs.406068.

3D structure databases

PDBe
RCSB-PDB
PDBj
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[»]
ProteinModelPortalP61081.
SMRP61081. Positions 27-183.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114504. 45 interactions.
DIPDIP-35679N.
IntActP61081. 11 interactions.
MINTMINT-5002641.
STRING9606.ENSP00000253023.

PTM databases

PhosphoSiteP61081.

Polymorphism databases

DMDM46577655.

2D gel databases

REPRODUCTION-2DPAGEIPI00022597.
UCD-2DPAGEP61081.

Proteomic databases

MaxQBP61081.
PaxDbP61081.
PeptideAtlasP61081.
PRIDEP61081.

Protocols and materials databases

DNASU9040.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000253023; ENSP00000253023; ENSG00000130725.
GeneID9040.
KEGGhsa:9040.
UCSCuc002qtl.4. human.

Organism-specific databases

CTD9040.
GeneCardsGC19M059067.
HGNCHGNC:12491. UBE2M.
HPACAB004993.
MIM603173. gene.
neXtProtNX_P61081.
PharmGKBPA37140.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5078.
HOGENOMHOG000233456.
HOVERGENHBG098591.
InParanoidP61081.
KOK10579.
OMAPDEGMYR.
OrthoDBEOG7SJD64.
PhylomeDBP61081.
TreeFamTF101125.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_6900. Immune System.
SignaLinkP61081.
UniPathwayUPA00885.

Gene expression databases

ArrayExpressP61081.
BgeeP61081.
CleanExHS_UBE2M.
GenevestigatorP61081.

Family and domain databases

Gene3D3.10.110.10. 1 hit.
InterProIPR000608. UBQ-conjugat_E2.
IPR023313. UBQ-conjugating_AS.
IPR016135. UBQ-conjugating_enzyme/RWD.
[Graphical view]
PfamPF00179. UQ_con. 1 hit.
[Graphical view]
SUPFAMSSF54495. SSF54495. 1 hit.
PROSITEPS00183. UBIQUITIN_CONJUGAT_1. 1 hit.
PS50127. UBIQUITIN_CONJUGAT_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSUBE2M. human.
EvolutionaryTraceP61081.
GeneWikiUBE2M.
GenomeRNAi9040.
NextBio33867.
PROP61081.
SOURCESearch...

Entry information

Entry nameUBC12_HUMAN
AccessionPrimary (citable) accession number: P61081
Secondary accession number(s): O76069, Q8VC50
Entry history
Integrated into UniProtKB/Swiss-Prot: April 26, 2004
Last sequence update: April 26, 2004
Last modified: July 9, 2014
This is version 113 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM