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   27-MAR-2024, entry version 172.
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       RIGI 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 RIGI and RNF135; involved in RIGI
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}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
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.ENSRNOP00000071283; -.
DR   iPTMnet; Q9EQX9; -.
DR   PhosphoSitePlus; Q9EQX9; -.
DR   SwissPalm; Q9EQX9; -.
DR   jPOST; Q9EQX9; -.
DR   PaxDb; 10116-ENSRNOP00000065259; -.
DR   Ensembl; ENSRNOT00000089874.2; ENSRNOP00000071283.1; ENSRNOG00000058053.2.
DR   Ensembl; ENSRNOT00055009893; ENSRNOP00055007651; ENSRNOG00055006099.
DR   Ensembl; ENSRNOT00060007715; ENSRNOP00060005780; ENSRNOG00060004628.
DR   Ensembl; ENSRNOT00065019543; ENSRNOP00065014979; ENSRNOG00065012014.
DR   GeneID; 116725; -.
DR   KEGG; rno:116725; -.
DR   UCSC; RGD:621096; rat.
DR   AGR; RGD:621096; -.
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; PDDYPME; -.
DR   OrthoDB; 5478564at2759; -.
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-445989; TAK1-dependent IKK and NF-kappa-B 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 cell types or tissues.
DR   GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR   GO; GO:0005829; C:cytosol; ISO:RGD.
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:0031371; C:ubiquitin conjugating enzyme complex; ISO:RGD.
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:0097027; F:ubiquitin-protein transferase activator activity; ISO:RGD.
DR   GO; GO:0004842; F:ubiquitin-protein transferase activity; IMP:RGD.
DR   GO; GO:0140374; P:antiviral innate immune response; ISO: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:1904262; P:negative regulation of TORC1 signaling; ISO:RGD.
DR   GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; 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:1902533; P:positive regulation of intracellular signal transduction; ISO:RGD.
DR   GO; GO:1902523; P:positive regulation of protein K63-linked ubiquitination; ISO:RGD.
DR   GO; GO:0006301; P:postreplication repair; ISO:RGD.
DR   GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISO:RGD.
DR   GO; GO:0070534; P:protein K63-linked ubiquitination; ISS:UniProtKB.
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; Ubiquitin Conjugating Enzyme; 1.
DR   InterPro; IPR000608; UBQ-conjugat_E2.
DR   InterPro; IPR023313; UBQ-conjugating_AS.
DR   InterPro; IPR016135; UBQ-conjugating_enzyme/RWD.
DR   PANTHER; PTHR24067:SF370; UBIQUITIN-CONJUGATING ENZYME; 1.
DR   PANTHER; PTHR24067; UBIQUITIN-CONJUGATING ENZYME E2; 1.
DR   Pfam; PF00179; UQ_con; 1.
DR   SMART; SM00212; UBCc; 1.
DR   SUPFAM; SSF54495; UBC-like; 1.
DR   PROSITE; PS00183; UBC_1; 1.
DR   PROSITE; PS50127; UBC_2; 1.
DR   Genevisible; Q9EQX9; RN.
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
//