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P61081

- UBC12_HUMAN

UniProt

P61081 - UBC12_HUMAN

Protein

NEDD8-conjugating enzyme Ubc12

Gene

UBE2M

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 115 (01 Oct 2014)
      Sequence version 1 (26 Apr 2004)
      Previous versions | rss
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    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

    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

    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.3 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 RBX1.5 Publications

    Binary interactionsi

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

    Protein-protein interaction databases

    BioGridi114504. 47 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.
    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

    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. 47 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

    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: October 1, 2014
    This is version 115 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