UBE2N_RAT
ID UBE2N_RAT Reviewed; 152 AA.
AC Q9EQX9;
DT 11-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Ubiquitin-conjugating enzyme E2 N;
DE EC=2.3.2.23;
DE AltName: Full=Bendless-like ubiquitin-conjugating enzyme;
DE AltName: Full=E2 ubiquitin-conjugating enzyme N;
DE AltName: Full=Ubiquitin carrier protein N;
DE AltName: Full=Ubiquitin-protein ligase N;
GN Name=Ube2n;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RA Takahashi H., Yamamoto M., Saito Y.;
RT "Expression of rat Bendless gene in the developing brain.";
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 [3]
RP PROTEIN SEQUENCE OF 34-68, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Hippocampus, and Spinal cord;
RA Lubec G., Afjehi-Sadat L., Diao W.;
RL Submitted (APR-2007) to UniProtKB.
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RA Maurya D.K., Bhargava P.;
RL Submitted (DEC-2008) to UniProtKB.
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-131, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: The UBE2V1-UBE2N and UBE2V2-UBE2N heterodimers catalyze the
CC synthesis of non-canonical 'Lys-63'-linked polyubiquitin chains. This
CC type of polyubiquitination does not lead to protein degradation by the
CC proteasome. Mediates transcriptional activation of target genes. Plays
CC a role in the control of progress through the cell cycle and
CC differentiation. Plays a role in the error-free DNA repair pathway and
CC contributes to the survival of cells after DNA damage. Acts together
CC with the E3 ligases, HLTF and SHPRH, in the 'Lys-63'-linked poly-
CC ubiquitination of PCNA upon genotoxic stress, which is required for DNA
CC repair. Appears to act together with E3 ligase RNF5 in the 'Lys-63'-
CC linked polyubiquitination of JKAMP thereby regulating JKAMP function by
CC decreasing its association with components of the proteasome and ERAD.
CC Promotes TRIM5 capsid-specific restriction activity and the UBE2V1-
CC UBE2N heterodimer acts in concert with TRIM5 to generate 'Lys-63'-
CC linked polyubiquitin chains which activate the MAP3K7/TAK1 complex
CC which in turn results in the induction and expression of NF-kappa-B and
CC MAPK-responsive inflammatory genes. Together with RNF135 and UB2V1,
CC catalyzes the viral RNA-dependent 'Lys-63'-linked polyubiquitination of
CC RIG-I/DDX58 to activate the downstream signaling pathway that leads to
CC interferon beta production (By similarity). UBE2V1-UBE2N together with
CC TRAF3IP2 E3 ubiquitin ligase mediate 'Lys-63'-linked polyubiquitination
CC of TRAF6, a component of IL17A-mediated signaling pathway.
CC {ECO:0000250|UniProtKB:P61088}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine +
CC [E2 ubiquitin-conjugating enzyme]-L-cysteine = [E1 ubiquitin-
CC activating enzyme]-L-cysteine + S-ubiquitinyl-[E2 ubiquitin-
CC conjugating enzyme]-L-cysteine.; EC=2.3.2.23;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00388, ECO:0000255|PROSITE-
CC ProRule:PRU10133};
CC -!- ACTIVITY REGULATION: Activity is inhibited by binding to OTUB1, which
CC prevents 'Lys-63'-linked polyubiquitination (By similarity). Activity
CC is inhibited by GPS2, leading to prevent 'Lys-63'-linked
CC polyubiquitination (By similarity). {ECO:0000250|UniProtKB:P61088,
CC ECO:0000250|UniProtKB:P61089}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000255|PROSITE-ProRule:PRU00388}.
CC -!- SUBUNIT: Heterodimer with UBE2V2 (By similarity). Interacts (UBE2V2-
CC UBE2N heterodimer) with the E3 ligase STUB1 (via the U-box domain); the
CC complex has a specific 'Lys-63'-linked polyubiquitination activity (By
CC similarity). Interacts with RNF8 and RNF168 (By similarity). Interacts
CC with RNF11 (By similarity). Interacts with the E3 ligases, HLTF and
CC SHPRH; the interactions promote the 'Lys-63'-linked polyubiquitination
CC of PCNA upon genotoxic stress and lead to DNA repair (By similarity).
CC Interacts with ARIH2 (via RING-type 2) (By similarity). Interacts with
CC OTUB1; leading to inhibit E2-conjugating activity (By similarity).
CC Interacts with GPS2; leading to inhibit E2-conjugating activity (By
CC similarity). Interacts with DDX58 and RNF135; involved in DDX58
CC ubiquitination and activation (By similarity).
CC {ECO:0000250|UniProtKB:P61088, ECO:0000250|UniProtKB:P61089}.
CC -!- PTM: Conjugation to ISG15 impairs formation of the thioester bond with
CC ubiquitin but not interaction with UBE2V2.
CC {ECO:0000250|UniProtKB:P61088}.
CC -!- SIMILARITY: Belongs to the ubiquitin-conjugating enzyme family.
CC {ECO:0000255|PROSITE-ProRule:PRU00388}.
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DR EMBL; AB032739; BAB20414.1; -; mRNA.
DR EMBL; BC090072; AAH90072.1; -; mRNA.
DR RefSeq; NP_446380.1; NM_053928.2.
DR AlphaFoldDB; Q9EQX9; -.
DR SMR; Q9EQX9; -.
DR BioGRID; 250592; 1.
DR IntAct; Q9EQX9; 1.
DR STRING; 10116.ENSRNOP00000065259; -.
DR iPTMnet; Q9EQX9; -.
DR PhosphoSitePlus; Q9EQX9; -.
DR SwissPalm; Q9EQX9; -.
DR jPOST; Q9EQX9; -.
DR PRIDE; Q9EQX9; -.
DR Ensembl; ENSRNOT00000089874; ENSRNOP00000071283; ENSRNOG00000058053.
DR GeneID; 116725; -.
DR KEGG; rno:116725; -.
DR UCSC; RGD:621096; rat.
DR CTD; 7334; -.
DR RGD; 621096; Ube2n.
DR eggNOG; KOG0417; Eukaryota.
DR GeneTree; ENSGT00540000070023; -.
DR HOGENOM; CLU_030988_13_2_1; -.
DR InParanoid; Q9EQX9; -.
DR OMA; QWKVNES; -.
DR OrthoDB; 1345547at2759; -.
DR PhylomeDB; Q9EQX9; -.
DR TreeFam; TF101126; -.
DR Reactome; R-RNO-1169408; ISG15 antiviral mechanism.
DR Reactome; R-RNO-168638; NOD1/2 Signaling Pathway.
DR Reactome; R-RNO-202424; Downstream TCR signaling.
DR Reactome; R-RNO-2871837; FCERI mediated NF-kB activation.
DR Reactome; R-RNO-450302; activated TAK1 mediates p38 MAPK activation.
DR Reactome; R-RNO-450321; JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
DR Reactome; R-RNO-5607764; CLEC7A (Dectin-1) signaling.
DR Reactome; R-RNO-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
DR Reactome; R-RNO-5693571; Nonhomologous End-Joining (NHEJ).
DR Reactome; R-RNO-5693607; Processing of DNA double-strand break ends.
DR Reactome; R-RNO-5696395; Formation of Incision Complex in GG-NER.
DR Reactome; R-RNO-69473; G2/M DNA damage checkpoint.
DR Reactome; R-RNO-8866654; E3 ubiquitin ligases ubiquitinate target proteins.
DR Reactome; R-RNO-9020702; Interleukin-1 signaling.
DR Reactome; R-RNO-937039; IRAK1 recruits IKK complex.
DR Reactome; R-RNO-9646399; Aggrephagy.
DR Reactome; R-RNO-975144; IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation.
DR Reactome; R-RNO-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR PRO; PR:Q9EQX9; -.
DR Proteomes; UP000002494; Chromosome 7.
DR Bgee; ENSRNOG00000058053; Expressed in testis and 20 other tissues.
DR Genevisible; Q9EQX9; RN.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005829; C:cytosol; ISO:RGD.
DR GO; GO:0001650; C:fibrillar center; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0032991; C:protein-containing complex; ISO:RGD.
DR GO; GO:0031372; C:UBC13-MMS2 complex; ISO:RGD.
DR GO; GO:0035370; C:UBC13-UEV1A complex; ISS:UniProtKB.
DR GO; GO:0000151; C:ubiquitin ligase complex; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0043130; F:ubiquitin binding; ISO:RGD.
DR GO; GO:0061631; F:ubiquitin conjugating enzyme activity; ISS:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:RGD.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IMP:RGD.
DR GO; GO:0000729; P:DNA double-strand break processing; ISO:RGD.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; ISO:RGD.
DR GO; GO:0016574; P:histone ubiquitination; ISO:RGD.
DR GO; GO:0045739; P:positive regulation of DNA repair; ISO:RGD.
DR GO; GO:2000781; P:positive regulation of double-strand break repair; ISO:RGD.
DR GO; GO:0031058; P:positive regulation of histone modification; ISO:RGD.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISO:RGD.
DR GO; GO:1902533; P:positive regulation of intracellular signal transduction; ISO:RGD.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISO:RGD.
DR GO; GO:1902523; P:positive regulation of protein K63-linked ubiquitination; ISO:RGD.
DR GO; GO:0051443; P:positive regulation of ubiquitin-protein transferase activity; ISO:RGD.
DR GO; GO:0006301; P:postreplication repair; ISO:RGD.
DR GO; GO:0070534; P:protein K63-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; IBA:GO_Central.
DR GO; GO:0016567; P:protein ubiquitination; ISO:RGD.
DR GO; GO:0033182; P:regulation of histone ubiquitination; ISO:RGD.
DR GO; GO:0050852; P:T cell receptor signaling pathway; ISO:RGD.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; ISO:RGD.
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; Direct protein sequencing; DNA damage;
KW DNA repair; Isopeptide bond; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Transferase; Ubl conjugation; Ubl conjugation pathway.
FT CHAIN 1..152
FT /note="Ubiquitin-conjugating enzyme E2 N"
FT /id="PRO_0000082506"
FT DOMAIN 3..149
FT /note="UBC core"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00388"
FT ACT_SITE 87
FT /note="Glycyl thioester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00388"
FT MOD_RES 82
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P61088"
FT MOD_RES 131
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT CROSSLNK 92
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ISG15)"
FT /evidence="ECO:0000250|UniProtKB:P61088"
SQ SEQUENCE 152 AA; 17124 MW; FACD84D883D27457 CRC64;
MAGLPRRIIK ETQRLLAEPV PGIKAEPDES NARYFHVVIA GPQDSPFEGG TFKLELFLPE
EYPMAAPKVR FMTKIYHPNV DKLGRICLDI LKDKWSPALQ IRTVLLSIQA LLSAPNPDDP
LANDVAEQWK SNEAQAIETA RAWTRLYAMN NI
