ID   UBE2N_MACFA             Reviewed;         152 AA.
AC   Q4R4I1;
DT   11-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT   19-JUL-2005, sequence version 1.
DT   27-MAR-2024, entry version 84.
DE   RecName: Full=Ubiquitin-conjugating enzyme E2 N;
DE            EC=2.3.2.23;
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; ORFNames=QtrA-13863;
OS   Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC   Cercopithecidae; Cercopithecinae; Macaca.
OX   NCBI_TaxID=9541;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Temporal cortex;
RG   International consortium for macaque cDNA sequencing and analysis;
RT   "DNA sequences of macaque genes expressed in brain or testis and its
RT   evolutionary implications.";
RL   Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
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.
CC       {ECO:0000250|UniProtKB:P61088}.
CC   -!- PATHWAY: Protein modification; protein ubiquitination.
CC       {ECO:0000255|PROSITE-ProRule:PRU00388}.
CC   -!- SUBUNIT: Heterodimer with UBE2V2. Interacts (UBE2V2-UBE2N heterodimer)
CC       with the E3 ligase STUB1 (via the U-box domain); the complex has a
CC       specific 'Lys-63'-linked polyubiquitination activity. Interacts with
CC       RNF8 and RNF168. Interacts with RNF11. Interacts with the E3 ligases,
CC       HLTF and SHPRH; the interactions promote the 'Lys-63'-linked
CC       polyubiquitination of PCNA upon genotoxic stress and lead to DNA
CC       repair. Interacts with ARIH2 (via RING-type 2). Interacts with OTUB1;
CC       leading to inhibit E2-conjugating activity. Interacts with RIGI and
CC       RNF135; involved in RIGI ubiquitination and activation (By similarity).
CC       {ECO:0000250|UniProtKB:P61088}.
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; AB169913; BAE01994.1; -; mRNA.
DR   RefSeq; NP_001271807.1; NM_001284878.1.
DR   AlphaFoldDB; Q4R4I1; -.
DR   BMRB; Q4R4I1; -.
DR   SMR; Q4R4I1; -.
DR   STRING; 9541.ENSMFAP00000045311; -.
DR   eggNOG; KOG0417; Eukaryota.
DR   OrthoDB; 5478564at2759; -.
DR   UniPathway; UPA00143; -.
DR   Proteomes; UP000233100; Unplaced.
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:0061631; F:ubiquitin conjugating enzyme activity; IEA:UniProtKB-EC.
DR   GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:UniProtKB.
DR   GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR   GO; GO:0070534; P:protein K63-linked ubiquitination; ISS:UniProtKB.
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.
PE   2: Evidence at transcript level;
KW   Acetylation; ATP-binding; DNA damage; DNA repair; Isopeptide bond;
KW   Nucleotide-binding; Reference proteome; Transferase; Ubl conjugation;
KW   Ubl conjugation pathway.
FT   CHAIN           1..152
FT                   /note="Ubiquitin-conjugating enzyme E2 N"
FT                   /id="PRO_0000082503"
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   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;  17112 MW;  E27627D883C5F697 CRC64;
     MAGLPRRIIK ETQRLLAEPV PGIKAEPDES NARYFHVVIA GPQDSPFEGG TFKLELFLPE
     EYPMAAPKVR FMTKIYHPNV DKSGRICLDI LKDKWSPALQ IRTVLLSIQA LLSAPNPDDP
     LANDVAEQWK TNEAQAIETA RAWTRLYAMN NI
//