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P61081

- UBC12_HUMAN

UniProt

P61081 - UBC12_HUMAN

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Protein

NEDD8-conjugating enzyme Ubc12

Gene
UBE2M, UBC12
Organism
Homo sapiens (Human)
Status
Reviewed - 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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei111 – 1111Glycyl thioester intermediate

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. NEDD8 ligase activity Source: UniProtKB
  3. protein binding Source: UniProtKB
  4. ribosomal S6-glutamic acid ligase activity Source: UniProtKB
  5. ubiquitin-protein transferase activity Source: UniProtKB

GO - Biological processi

  1. cellular protein modification process Source: UniProtKB
  2. positive regulation of neuron apoptotic process Source: Ensembl
  3. protein neddylation Source: UniProtKB
  4. protein ubiquitination Source: GOC
  5. 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

ReactomeiREACT_120850. TGF-beta receptor signaling activates SMADs.
REACT_75842. 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
ProteomesiUP000005640: Chromosome 19

Organism-specific databases

HGNCiHGNC:12491. UBE2M.

Subcellular locationi

GO - Cellular componenti

  1. cytosol Source: Reactome
  2. extracellular vesicular exosome Source: UniProt
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.

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-acetylmethionine3 Publications
Modified residuei3 – 31N6-acetyllysine1 Publication
Modified residuei50 – 501Phosphoserine1 Publication

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

MaxQBiP61081.
PaxDbiP61081.
PeptideAtlasiP61081.
PRIDEiP61081.

2D gel databases

REPRODUCTION-2DPAGEIPI00022597.
UCD-2DPAGEP61081.

PTM databases

PhosphoSiteiP61081.

Expressioni

Gene expression databases

ArrayExpressiP61081.
BgeeiP61081.
CleanExiHS_UBE2M.
GenevestigatoriP61081.

Organism-specific databases

HPAiCAB004993.

Interactioni

Subunit structurei

Interacts with UBA3, DCUN1D1 and RBX1.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
CUL1Q136162EBI-1041660,EBI-359390
NEDD8Q158432EBI-1041660,EBI-716247
UBA3Q8TBC42EBI-1041660,EBI-717567

Protein-protein interaction databases

BioGridi114504. 45 interactions.
DIPiDIP-35679N.
IntActiP61081. 11 interactions.
MINTiMINT-5002641.
STRINGi9606.ENSP00000253023.

Structurei

Secondary structure

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

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
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[»]
ProteinModelPortaliP61081.
SMRiP61081. Positions 27-183.

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

Phylogenomic databases

eggNOGiCOG5078.
HOGENOMiHOG000233456.
HOVERGENiHBG098591.
InParanoidiP61081.
KOiK10579.
OMAiPDEGMYR.
OrthoDBiEOG7SJD64.
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

MIKLFSLKQQ KKEEESAGGT KGSSKKASAA QLRIQKDINE LNLPKTCDIS    50
FSDPDDLLNF KLVICPDEGF YKSGKFVFSF KVGQGYPHDP PKVKCETMVY 100
HPNIDLEGNV CLNILREDWK PVLTINSIIY GLQYLFLEPN PEDPLNKEAA 150
EVLQNNRRLF EQNVQRSMRG GYIGSTYFER CLK 183
Length:183
Mass (Da):20,900
Last modified:April 26, 2004 - v1
Checksum:iE3C288CA6A98BC5C
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.4. human.

Polymorphism databases

DMDMi46577655.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.
UniGenei Hs.406068.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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 [» ]
ProteinModelPortali P61081.
SMRi P61081. Positions 27-183.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 114504. 45 interactions.
DIPi DIP-35679N.
IntActi P61081. 11 interactions.
MINTi MINT-5002641.
STRINGi 9606.ENSP00000253023.

PTM databases

PhosphoSitei P61081.

Polymorphism databases

DMDMi 46577655.

2D gel databases

REPRODUCTION-2DPAGE IPI00022597.
UCD-2DPAGE P61081.

Proteomic databases

MaxQBi P61081.
PaxDbi P61081.
PeptideAtlasi P61081.
PRIDEi P61081.

Protocols and materials databases

DNASUi 9040.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000253023 ; ENSP00000253023 ; ENSG00000130725 .
GeneIDi 9040.
KEGGi hsa:9040.
UCSCi uc002qtl.4. human.

Organism-specific databases

CTDi 9040.
GeneCardsi GC19M059067.
HGNCi HGNC:12491. UBE2M.
HPAi CAB004993.
MIMi 603173. gene.
neXtProti NX_P61081.
PharmGKBi PA37140.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG5078.
HOGENOMi HOG000233456.
HOVERGENi HBG098591.
InParanoidi P61081.
KOi K10579.
OMAi PDEGMYR.
OrthoDBi EOG7SJD64.
PhylomeDBi P61081.
TreeFami TF101125.

Enzyme and pathway databases

UniPathwayi UPA00885 .
Reactomei REACT_120850. TGF-beta receptor signaling activates SMADs.
REACT_75842. Antigen processing: Ubiquitination & Proteasome degradation.
SignaLinki P61081.

Miscellaneous databases

ChiTaRSi UBE2M. human.
EvolutionaryTracei P61081.
GeneWikii UBE2M.
GenomeRNAii 9040.
NextBioi 33867.
PROi P61081.
SOURCEi Search...

Gene expression databases

ArrayExpressi P61081.
Bgeei P61081.
CleanExi HS_UBE2M.
Genevestigatori P61081.

Family and domain databases

Gene3Di 3.10.110.10. 1 hit.
InterProi IPR000608. UBQ-conjugat_E2.
IPR023313. UBQ-conjugating_AS.
IPR016135. UBQ-conjugating_enzyme/RWD.
[Graphical view ]
Pfami PF00179. UQ_con. 1 hit.
[Graphical view ]
SUPFAMi SSF54495. SSF54495. 1 hit.
PROSITEi PS00183. UBIQUITIN_CONJUGAT_1. 1 hit.
PS50127. UBIQUITIN_CONJUGAT_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. 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. 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. 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.

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 3, 2014
This is version 114 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

External Data

Dasty 3

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