UBC12_MOUSE
ID UBC12_MOUSE Reviewed; 183 AA.
AC P61082; O76069; Q8VC50;
DT 26-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2004, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=NEDD8-conjugating enzyme Ubc12;
DE EC=2.3.2.34 {ECO:0000250|UniProtKB:P61081};
DE AltName: Full=NEDD8 carrier protein;
DE AltName: Full=Ubiquitin-conjugating enzyme E2 M;
GN Name=Ube2m; Synonyms=Ubc-rs2, Ubc12;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [2]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [3]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-169, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Embryo;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
CC -!- FUNCTION: Accepts the ubiquitin-like protein NEDD8 from the UBA3-NAE1
CC E1 complex and catalyzes its covalent attachment to other proteins. The
CC specific interaction with the E3 ubiquitin ligase RBX1, but not RBX2,
CC suggests that the RBX1-UBE2M complex neddylates specific target
CC proteins, such as CUL1, CUL2, CUL3 and CUL4. Involved in cell
CC proliferation. {ECO:0000250|UniProtKB:P61081}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine +
CC [E2 NEDD8-conjugating enzyme]-L-cysteine = [E1 NEDD8-activating
CC enzyme]-L-cysteine + [E2 NEDD8-conjugating enzyme]-S-[NEDD8-protein]-
CC yl-L-cysteine.; EC=2.3.2.34; Evidence={ECO:0000250|UniProtKB:P61081};
CC -!- PATHWAY: Protein modification; protein neddylation.
CC -!- SUBUNIT: Interacts with UBA3 and RBX1. Interacts (N-terminally
CC acetylated form) with (via DCUN1 domain) DCUN1D1, DCUN1D2, DCUN1D3,
CC DCUN1D4 and DCUN1D5. {ECO:0000250|UniProtKB:P61081}.
CC -!- DOMAIN: Both the N-terminal docking peptide and the catalytic core
CC domain must bind the UBA3-NAE1 complex simultaneously for optimal
CC transfer of NEDD8. {ECO:0000250}.
CC -!- PTM: The acetylation of Met-1 increases affinity for DCUN1D1 by about 2
CC orders of magnitude and is crucial for NEDD8 transfer to cullins.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the ubiquitin-conjugating enzyme family. UBC12
CC subfamily. {ECO:0000255|PROSITE-ProRule:PRU00388}.
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DR EMBL; BC021792; AAH21792.1; -; mRNA.
DR CCDS; CCDS20825.1; -.
DR RefSeq; NP_663553.1; NM_145578.3.
DR AlphaFoldDB; P61082; -.
DR SMR; P61082; -.
DR BioGRID; 204404; 7.
DR IntAct; P61082; 1.
DR MINT; P61082; -.
DR STRING; 10090.ENSMUSP00000005714; -.
DR iPTMnet; P61082; -.
DR PhosphoSitePlus; P61082; -.
DR SwissPalm; P61082; -.
DR REPRODUCTION-2DPAGE; IPI00169448; -.
DR REPRODUCTION-2DPAGE; P61082; -.
DR EPD; P61082; -.
DR jPOST; P61082; -.
DR MaxQB; P61082; -.
DR PaxDb; P61082; -.
DR PeptideAtlas; P61082; -.
DR PRIDE; P61082; -.
DR ProteomicsDB; 298445; -.
DR Antibodypedia; 3333; 203 antibodies from 34 providers.
DR DNASU; 22192; -.
DR Ensembl; ENSMUST00000005714; ENSMUSP00000005714; ENSMUSG00000005575.
DR GeneID; 22192; -.
DR KEGG; mmu:22192; -.
DR UCSC; uc009ffd.2; mouse.
DR CTD; 9040; -.
DR MGI; MGI:108278; Ube2m.
DR VEuPathDB; HostDB:ENSMUSG00000005575; -.
DR eggNOG; KOG0420; Eukaryota.
DR GeneTree; ENSGT00940000162814; -.
DR HOGENOM; CLU_030988_6_0_1; -.
DR InParanoid; P61082; -.
DR OMA; GYPHDAP; -.
DR OrthoDB; 1302735at2759; -.
DR PhylomeDB; P61082; -.
DR TreeFam; TF101125; -.
DR Reactome; R-MMU-2173789; TGF-beta receptor signaling activates SMADs.
DR Reactome; R-MMU-5607761; Dectin-1 mediated noncanonical NF-kB signaling.
DR Reactome; R-MMU-5676590; NIK-->noncanonical NF-kB signaling.
DR Reactome; R-MMU-8951664; Neddylation.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00885; -.
DR BioGRID-ORCS; 22192; 32 hits in 71 CRISPR screens.
DR ChiTaRS; Ube2m; mouse.
DR PRO; PR:P61082; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; P61082; protein.
DR Bgee; ENSMUSG00000005575; Expressed in superior frontal gyrus and 252 other tissues.
DR ExpressionAtlas; P61082; baseline and differential.
DR Genevisible; P61082; MM.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019788; F:NEDD8 transferase activity; ISS:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:UniProtKB.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; ISO:MGI.
DR GO; GO:0036211; P:protein modification process; ISS:UniProtKB.
DR GO; GO:0045116; P:protein neddylation; ISS:UniProtKB.
DR CDD; cd00195; UBCc; 1.
DR Gene3D; 3.10.110.10; -; 1.
DR InterPro; IPR000608; UBQ-conjugat_E2.
DR InterPro; IPR023313; UBQ-conjugating_AS.
DR InterPro; IPR016135; UBQ-conjugating_enzyme/RWD.
DR Pfam; PF00179; UQ_con; 1.
DR SUPFAM; SSF54495; SSF54495; 1.
DR PROSITE; PS00183; UBC_1; 1.
DR PROSITE; PS50127; UBC_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; ATP-binding; Methylation; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Transferase; Ubl conjugation pathway.
FT CHAIN 1..183
FT /note="NEDD8-conjugating enzyme Ubc12"
FT /id="PRO_0000082489"
FT DOMAIN 29..173
FT /note="UBC core"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00388"
FT REGION 1..57
FT /note="Interaction with UBA3"
FT /evidence="ECO:0000250"
FT REGION 1..29
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..20
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 111
FT /note="Glycyl thioester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00388,
FT ECO:0000255|PROSITE-ProRule:PRU10133"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P61081"
FT MOD_RES 3
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P61081"
FT MOD_RES 50
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P61081"
FT MOD_RES 169
FT /note="Asymmetric dimethylarginine; alternate"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 169
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0007744|PubMed:24129315"
SQ SEQUENCE 183 AA; 20900 MW; E3C288CA6A98BC5C CRC64;
MIKLFSLKQQ KKEEESAGGT KGSSKKASAA QLRIQKDINE LNLPKTCDIS FSDPDDLLNF
KLVICPDEGF YKSGKFVFSF KVGQGYPHDP PKVKCETMVY HPNIDLEGNV CLNILREDWK
PVLTINSIIY GLQYLFLEPN PEDPLNKEAA EVLQNNRRLF EQNVQRSMRG GYIGSTYFER
CLK
