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Database: UniProt
Entry: P61088
LinkDB: P61088
Original site: P61088 
ID   UBE2N_HUMAN             Reviewed;         152 AA.
AC   P61088; Q16781; Q53Y81;
DT   26-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT   26-APR-2004, sequence version 1.
DT   07-APR-2021, entry version 196.
DE   RecName: Full=Ubiquitin-conjugating enzyme E2 N;
DE            EC=2.3.2.23 {ECO:0000269|PubMed:20061386};
DE   AltName: Full=Bendless-like ubiquitin-conjugating enzyme;
DE   AltName: Full=E2 ubiquitin-conjugating enzyme N;
DE   AltName: Full=Ubc13;
DE   AltName: Full=UbcH13;
DE   AltName: Full=Ubiquitin carrier protein N;
DE   AltName: Full=Ubiquitin-protein ligase N;
GN   Name=UBE2N; Synonyms=BLU;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=8902611; DOI=10.1093/oxfordjournals.jbchem.a021440;
RA   Yamaguchi T., Kim N.-S., Sekine S., Seino H., Osaka F., Yamao F., Kato S.;
RT   "Cloning and expression of cDNA encoding a human ubiquitin-conjugating
RT   enzyme similar to the Drosophila bendless gene product.";
RL   J. Biochem. 120:494-497(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA   Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA   Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA   Phelan M., Farmer A.;
RT   "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL   Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Lung, Placenta, and Uterus;
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   [4]
RP   PROTEIN SEQUENCE OF 15-24; 34-68; 86-92 AND 95-102, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY.
RC   TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA   Lubec G., Vishwanath V., Chen W.-Q., Sun Y.;
RL   Submitted (DEC-2008) to UniProtKB.
RN   [5]
RP   PROTEIN SEQUENCE OF 86-94, MUTAGENESIS OF LYS-92, ISGYLATION AT LYS-92, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY.
RX   PubMed=16122702; DOI=10.1016/j.bbrc.2005.08.038;
RA   Zou W., Papov V., Malakhova O., Kim K.I., Dao C., Li J., Zhang D.-E.;
RT   "ISG15 modification of ubiquitin E2 Ubc13 disrupts its ability to form
RT   thioester bond with ubiquitin.";
RL   Biochem. Biophys. Res. Commun. 336:61-68(2005).
RN   [6]
RP   FUNCTION, AND INTERACTION WITH UBE2V2.
RX   PubMed=10089880; DOI=10.1016/s0092-8674(00)80575-9;
RA   Hofmann R.M., Pickart C.M.;
RT   "Noncanonical MMS2-encoded ubiquitin-conjugating enzyme functions in
RT   assembly of novel polyubiquitin chains for DNA repair.";
RL   Cell 96:645-653(1999).
RN   [7]
RP   FUNCTION, AND INTERACTION WITH UBE2V2.
RX   PubMed=14562038; DOI=10.1038/sj.onc.1206831;
RA   Bothos J., Summers M.K., Venere M., Scolnick D.M., Halazonetis T.D.;
RT   "The Chfr mitotic checkpoint protein functions with Ubc13-Mms2 to form
RT   Lys63-linked polyubiquitin chains.";
RL   Oncogene 22:7101-7107(2003).
RN   [8]
RP   MUTAGENESIS OF LYS-92 AND LYS-94, AND ISGYLATION AT LYS-92.
RX   PubMed=16112642; DOI=10.1016/j.bbrc.2005.08.034;
RA   Takeuchi T., Yokosawa H.;
RT   "ISG15 modification of Ubc13 suppresses its ubiquitin-conjugating
RT   activity.";
RL   Biochem. Biophys. Res. Commun. 336:9-13(2005).
RN   [9]
RP   INTERACTION WITH SHPRH, AND MUTAGENESIS OF CYS-87.
RX   PubMed=17130289; DOI=10.1083/jcb.200606145;
RA   Motegi A., Sood R., Moinova H., Markowitz S.D., Liu P.P., Myung K.;
RT   "Human SHPRH suppresses genomic instability through proliferating cell
RT   nuclear antigen polyubiquitination.";
RL   J. Cell Biol. 175:703-708(2006).
RN   [10]
RP   INTERACTION WITH RNF8.
RX   PubMed=16215985; DOI=10.1002/jcb.20587;
RA   Plans V., Scheper J., Soler M., Loukili N., Okano Y., Thomson T.M.;
RT   "The RING finger protein RNF8 recruits UBC13 for lysine 63-based self
RT   polyubiquitylation.";
RL   J. Cell. Biochem. 97:572-582(2006).
RN   [11]
RP   INTERACTION WITH SHPRH.
RX   PubMed=17108083; DOI=10.1073/pnas.0608595103;
RA   Unk I., Hajdu I., Fatyol K., Szakal B., Blastyak A., Bermudez V.,
RA   Hurwitz J., Prakash L., Prakash S., Haracska L.;
RT   "Human SHPRH is a ubiquitin ligase for Mms2-Ubc13-dependent
RT   polyubiquitylation of proliferating cell nuclear antigen.";
RL   Proc. Natl. Acad. Sci. U.S.A. 103:18107-18112(2006).
RN   [12]
RP   MUTAGENESIS OF CYS-87.
RX   PubMed=17135271; DOI=10.1074/jbc.m609503200;
RA   Lamothe B., Besse A., Campos A.D., Webster W.K., Wu H., Darnay B.G.;
RT   "Site-specific Lys-63-linked tumor necrosis factor receptor-associated
RT   factor 6 auto-ubiquitination is a critical determinant of I kappa B kinase
RT   activation.";
RL   J. Biol. Chem. 282:4102-4112(2007).
RN   [13]
RP   INTERACTION WITH HLTF.
RX   PubMed=18316726; DOI=10.1073/pnas.0800563105;
RA   Unk I., Hajdu I., Fatyol K., Hurwitz J., Yoon J.-H., Prakash L.,
RA   Prakash S., Haracska L.;
RT   "Human HLTF functions as a ubiquitin ligase for proliferating cell nuclear
RT   antigen polyubiquitination.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:3768-3773(2008).
RN   [14]
RP   INTERACTION WITH HLTF.
RX   PubMed=18719106; DOI=10.1073/pnas.0805685105;
RA   Motegi A., Liaw H.-J., Lee K.-Y., Roest H.P., Maas A., Wu X., Moinova H.,
RA   Markowitz S.D., Ding H., Hoeijmakers J.H.J., Myung K.;
RT   "Polyubiquitination of proliferating cell nuclear antigen by HLTF and SHPRH
RT   prevents genomic instability from stalled replication forks.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:12411-12416(2008).
RN   [15]
RP   INTERACTION WITH RNF168.
RX   PubMed=19203578; DOI=10.1016/j.cell.2008.12.042;
RA   Stewart G.S., Panier S., Townsend K., Al-Hakim A.K., Kolas N.K.,
RA   Miller E.S., Nakada S., Ylanko J., Olivarius S., Mendez M., Oldreive C.,
RA   Wildenhain J., Tagliaferro A., Pelletier L., Taubenheim N., Durandy A.,
RA   Byrd P.J., Stankovic T., Taylor A.M.R., Durocher D.;
RT   "The RIDDLE syndrome protein mediates a ubiquitin-dependent signaling
RT   cascade at sites of DNA damage.";
RL   Cell 136:420-434(2009).
RN   [16]
RP   FUNCTION IN UBIQUITINATION OF JKAMP.
RX   PubMed=19269966; DOI=10.1074/jbc.m808222200;
RA   Tcherpakov M., Delaunay A., Toth J., Kadoya T., Petroski M.D., Ronai Z.A.;
RT   "Regulation of endoplasmic reticulum-associated degradation by RNF5-
RT   dependent ubiquitination of JNK-associated membrane protein (JAMP).";
RL   J. Biol. Chem. 284:12099-12109(2009).
RN   [17]
RP   INTERACTION WITH ARIH2, AND SUBCELLULAR LOCATION.
RX   PubMed=19340006; DOI=10.1038/leu.2009.57;
RA   Marteijn J.A., van der Meer L.T., Smit J.J., Noordermeer S.M., Wissink W.,
RA   Jansen P., Swarts H.G., Hibbert R.G., de Witte T., Sixma T.K., Jansen J.H.,
RA   van der Reijden B.A.;
RT   "The ubiquitin ligase Triad1 inhibits myelopoiesis through UbcH7 and Ubc13
RT   interacting domains.";
RL   Leukemia 23:1480-1489(2009).
RN   [18]
RP   INTERACTION WITH RNF11.
RX   PubMed=18615712; DOI=10.1002/prot.22120;
RA   Scheper J., Oliva B., Villa-Freixa J., Thomson T.M.;
RT   "Analysis of electrostatic contributions to the selectivity of interactions
RT   between RING-finger domains and ubiquitin-conjugating enzymes.";
RL   Proteins 74:92-103(2009).
RN   [19]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-82, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19608861; DOI=10.1126/science.1175371;
RA   Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA   Olsen J.V., Mann M.;
RT   "Lysine acetylation targets protein complexes and co-regulates major
RT   cellular functions.";
RL   Science 325:834-840(2009).
RN   [20]
RP   FUNCTION.
RX   PubMed=19825828; DOI=10.1126/scisignal.2000382;
RA   Liu C., Qian W., Qian Y., Giltiay N.V., Lu Y., Swaidani S., Misra S.,
RA   Deng L., Chen Z.J., Li X.;
RT   "Act1, a U-box E3 ubiquitin ligase for IL-17 signaling.";
RL   Sci. Signal. 2:ra63-ra63(2009).
RN   [21]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=20061386; DOI=10.1074/jbc.m109.089003;
RA   David Y., Ziv T., Admon A., Navon A.;
RT   "The E2 ubiquitin-conjugating enzymes direct polyubiquitination to
RT   preferred lysines.";
RL   J. Biol. Chem. 285:8595-8604(2010).
RN   [22]
RP   ACTIVITY REGULATION, AND INTERACTION WITH OTUB1.
RX   PubMed=20725033; DOI=10.1038/nature09297;
RA   Nakada S., Tai I., Panier S., Al-Hakim A., Iemura S., Juang Y.C.,
RA   O'Donnell L., Kumakubo A., Munro M., Sicheri F., Gingras A.C., Natsume T.,
RA   Suda T., Durocher D.;
RT   "Non-canonical inhibition of DNA damage-dependent ubiquitination by
RT   OTUB1.";
RL   Nature 466:941-946(2010).
RN   [23]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [24]
RP   FUNCTION.
RX   PubMed=21512573; DOI=10.1038/nature09976;
RA   Pertel T., Hausmann S., Morger D., Zueger S., Guerra J., Lascano J.,
RA   Reinhard C., Santoni F.A., Uchil P.D., Chatel L., Bisiaux A., Albert M.L.,
RA   Strambio-De-Castillia C., Mothes W., Pizzato M., Gruetter M.G., Luban J.;
RT   "TRIM5 is an innate immune sensor for the retrovirus capsid lattice.";
RL   Nature 472:361-365(2011).
RN   [25]
RP   IDENTIFICATION BY MASS SPECTROMETRY.
RX   PubMed=21659603; DOI=10.1126/science.1203430;
RA   Cotta-Ramusino C., McDonald E.R. III, Hurov K., Sowa M.E., Harper J.W.,
RA   Elledge S.J.;
RT   "A DNA damage response screen identifies RHINO, a 9-1-1 and TopBP1
RT   interacting protein required for ATR signaling.";
RL   Science 332:1313-1317(2011).
RN   [26]
RP   ISGYLATION, AND DISULFIDE BOND.
RX   PubMed=22693631; DOI=10.1371/journal.pone.0038294;
RA   Bade V.N., Nickels J., Keusekotten K., Praefcke G.J.;
RT   "Covalent protein modification with ISG15 via a conserved cysteine in the
RT   hinge region.";
RL   PLoS ONE 7:E38294-E38294(2012).
RN   [27]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=25944712; DOI=10.1002/pmic.201400617;
RA   Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA   Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT   "N-terminome analysis of the human mitochondrial proteome.";
RL   Proteomics 15:2519-2524(2015).
RN   [28]
RP   FUNCTION, AND INTERACTION WITH DDX58 AND RNF135.
RX   PubMed=28469175; DOI=10.1038/ncomms15138;
RA   Shi Y., Yuan B., Zhu W., Zhang R., Li L., Hao X., Chen S., Hou F.;
RT   "Ube2D3 and Ube2N are essential for RIG-I-mediated MAVS aggregation in
RT   antiviral innate immunity.";
RL   Nat. Commun. 8:15138-15138(2017).
RN   [29]
RP   FUNCTION.
RX   PubMed=31006531; DOI=10.1016/j.cell.2019.03.017;
RA   Cadena C., Ahmad S., Xavier A., Willemsen J., Park S., Park J.W., Oh S.W.,
RA   Fujita T., Hou F., Binder M., Hur S.;
RT   "Ubiquitin-Dependent and -Independent Roles of E3 Ligase RIPLET in Innate
RT   Immunity.";
RL   Cell 177:1187-1200(2019).
RN   [30]
RP   X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) IN COMPLEX WITH UBE2V2.
RX   PubMed=11473255; DOI=10.1038/90373;
RA   Moraes T.F., Edwards R.A., McKenna S., Pastushok L., Xiao W.,
RA   Glover J.N.M., Ellison M.J.;
RT   "Crystal structure of the human ubiquitin conjugating enzyme complex,
RT   hMms2-hUbc13.";
RL   Nat. Struct. Biol. 8:669-673(2001).
RN   [31]
RP   X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 2-152 IN COMPLEX WITH STUB1 AND
RP   UBE2V1.
RX   PubMed=16307917; DOI=10.1016/j.molcel.2005.09.023;
RA   Zhang M., Windheim M., Roe S.M., Peggie M., Cohen P., Prodromou C.,
RA   Pearl L.H.;
RT   "Chaperoned ubiquitylation -- crystal structures of the CHIP U box E3
RT   ubiquitin ligase and a CHIP-Ubc13-Uev1a complex.";
RL   Mol. Cell 20:525-538(2005).
RN   [32]
RP   X-RAY CRYSTALLOGRAPHY (4.8 ANGSTROMS) OF 1-150 IN COMPLEX WITH RNF8 AND
RP   UBE2V2.
RX   PubMed=22589545; DOI=10.1074/jbc.m112.359653;
RA   Campbell S.J., Edwards R.A., Leung C.C., Neculai D., Hodge C.D.,
RA   Dhe-Paganon S., Glover J.N.;
RT   "Molecular insights into the function of RING Finger (RNF)-containing
RT   proteins hRNF8 and hRNF168 in Ubc13/Mms2-dependent ubiquitylation.";
RL   J. Biol. Chem. 287:23900-23910(2012).
RN   [33]
RP   X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS) OF 25-271 IN COMPLEX WITH UBE2V2 AND
RP   OTUB1, ACTIVITY REGULATION, AND INTERACTION WITH OTUB1.
RX   PubMed=22325355; DOI=10.1016/j.molcel.2012.01.011;
RA   Juang Y.C., Landry M.C., Sanches M., Vittal V., Leung C.C.,
RA   Ceccarelli D.F., Mateo A.R., Pruneda J.N., Mao D.Y., Szilard R.K.,
RA   Orlicky S., Munro M., Brzovic P.S., Klevit R.E., Sicheri F., Durocher D.;
RT   "OTUB1 co-opts Lys48-linked ubiquitin recognition to suppress E2 enzyme
RT   function.";
RL   Mol. Cell 45:384-397(2012).
RN   [34]
RP   X-RAY CRYSTALLOGRAPHY (3.11 ANGSTROMS) IN COMPLEX WITH OUTB1 AND UBIQUITIN,
RP   ACTIVITY REGULATION, AND INTERACTION WITH OTUB1.
RX   PubMed=22367539; DOI=10.1038/nature10911;
RA   Wiener R., Zhang X., Wang T., Wolberger C.;
RT   "The mechanism of OTUB1-mediated inhibition of ubiquitination.";
RL   Nature 483:618-622(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 (PubMed:28469175, PubMed:31006531). UBE2V1-
CC       UBE2N together with TRAF3IP2 E3 ubiquitin ligase mediate 'Lys-63'-
CC       linked polyubiquitination of TRAF6, a component of IL17A-mediated
CC       signaling pathway. {ECO:0000269|PubMed:10089880,
CC       ECO:0000269|PubMed:14562038, ECO:0000269|PubMed:19269966,
CC       ECO:0000269|PubMed:19825828, ECO:0000269|PubMed:20061386,
CC       ECO:0000269|PubMed:21512573, ECO:0000269|PubMed:28469175,
CC       ECO:0000269|PubMed:31006531}.
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, ECO:0000269|PubMed:20061386};
CC   -!- ACTIVITY REGULATION: Activity is inhibited by binding to OTUB1, which
CC       prevents 'Lys-63'-linked polyubiquitination (PubMed:20725033,
CC       PubMed:22325355, PubMed:22367539). Activity is inhibited by GPS2,
CC       leading to prevent 'Lys-63'-linked polyubiquitination (By similarity).
CC       {ECO:0000250|UniProtKB:P61089, ECO:0000269|PubMed:20725033,
CC       ECO:0000269|PubMed:22325355, ECO:0000269|PubMed:22367539}.
CC   -!- PATHWAY: Protein modification; protein ubiquitination.
CC       {ECO:0000255|PROSITE-ProRule:PRU00388}.
CC   -!- SUBUNIT: Heterodimer with UBE2V2 (PubMed:10089880, PubMed:11473255,
CC       PubMed:14562038, PubMed:16307917, PubMed:16307917). 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
CC       (PubMed:16307917). Interacts with RNF8 and RNF168 (PubMed:16215985,
CC       PubMed:19203578). Interacts with RNF11 (PubMed:18615712). Interacts
CC       with the E3 ligases, HLTF and SHPRH; the interactions promote the 'Lys-
CC       63'-linked polyubiquitination of PCNA upon genotoxic stress and lead to
CC       DNA repair (PubMed:17108083, PubMed:17130289, PubMed:18316726,
CC       PubMed:18719106). Interacts with ARIH2 (via RING-type 2)
CC       (PubMed:19340006). Interacts with OTUB1; leading to inhibit E2-
CC       conjugating activity (PubMed:20725033, PubMed:22325355,
CC       PubMed:22367539). Interacts with GPS2; leading to inhibit E2-
CC       conjugating activity (By similarity). Interacts with DDX58 and RNF135;
CC       involved in DDX58 ubiquitination and activation (PubMed:28469175).
CC       {ECO:0000250|UniProtKB:P61089, ECO:0000269|PubMed:10089880,
CC       ECO:0000269|PubMed:11473255, ECO:0000269|PubMed:14562038,
CC       ECO:0000269|PubMed:16215985, ECO:0000269|PubMed:16307917,
CC       ECO:0000269|PubMed:17108083, ECO:0000269|PubMed:17130289,
CC       ECO:0000269|PubMed:18316726, ECO:0000269|PubMed:18615712,
CC       ECO:0000269|PubMed:18719106, ECO:0000269|PubMed:19203578,
CC       ECO:0000269|PubMed:19340006, ECO:0000269|PubMed:20725033,
CC       ECO:0000269|PubMed:22325355, ECO:0000269|PubMed:22367539,
CC       ECO:0000269|PubMed:22589545, ECO:0000269|PubMed:28469175}.
CC   -!- INTERACTION:
CC       P61088; Q13489: BIRC3; NbExp=2; IntAct=EBI-1052908, EBI-517709;
CC       P61088; Q14527: HLTF; NbExp=4; IntAct=EBI-1052908, EBI-1045161;
CC       P61088; Q6UWE0: LRSAM1; NbExp=3; IntAct=EBI-1052908, EBI-720984;
CC       P61088; Q96FW1-1: OTUB1; NbExp=5; IntAct=EBI-1052908, EBI-15972141;
CC       P61088; Q9BYM8: RBCK1; NbExp=2; IntAct=EBI-1052908, EBI-2340624;
CC       P61088; Q6PCD5: RFWD3; NbExp=2; IntAct=EBI-1052908, EBI-2129159;
CC       P61088; Q9Y3C5: RNF11; NbExp=4; IntAct=EBI-1052908, EBI-396669;
CC       P61088; O43567: RNF13; NbExp=2; IntAct=EBI-1052908, EBI-2129183;
CC       P61088; Q8IYW5: RNF168; NbExp=2; IntAct=EBI-1052908, EBI-914207;
CC       P61088; Q8N6D2: RNF182; NbExp=2; IntAct=EBI-1052908, EBI-2130099;
CC       P61088; Q149N8-1: SHPRH; NbExp=2; IntAct=EBI-1052908, EBI-15612386;
CC       P61088; Q9UNE7: STUB1; NbExp=5; IntAct=EBI-1052908, EBI-357085;
CC       P61088; Q9Y4K3: TRAF6; NbExp=8; IntAct=EBI-1052908, EBI-359276;
CC       P61088; Q13049: TRIM32; NbExp=3; IntAct=EBI-1052908, EBI-742790;
CC       P61088; Q13404: UBE2V1; NbExp=18; IntAct=EBI-1052908, EBI-1050671;
CC       P61088; Q13404-2: UBE2V1; NbExp=2; IntAct=EBI-1052908, EBI-15972179;
CC       P61088; Q15819: UBE2V2; NbExp=4; IntAct=EBI-1052908, EBI-714329;
CC       P61088; P98170: XIAP; NbExp=2; IntAct=EBI-1052908, EBI-517127;
CC       P61088; Q8ND25: ZNRF1; NbExp=4; IntAct=EBI-1052908, EBI-2129250;
CC       P61088; Q62925: Map3k1; Xeno; NbExp=46; IntAct=EBI-1052908, EBI-636664;
CC       P61088; Q8VSD5: ORF169b; Xeno; NbExp=2; IntAct=EBI-1052908, EBI-15974371;
CC       P61088; Q9XVR6: otub-1; Xeno; NbExp=2; IntAct=EBI-1052908, EBI-316044;
CC       P61088; Q9WUD1: Stub1; Xeno; NbExp=2; IntAct=EBI-1052908, EBI-773027;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:19340006}. Cytoplasm
CC       {ECO:0000269|PubMed:19340006}.
CC   -!- PTM: Conjugation to ISG15 impairs formation of the thioester bond with
CC       ubiquitin but not interaction with UBE2V2.
CC       {ECO:0000269|PubMed:16112642}.
CC   -!- SIMILARITY: Belongs to the ubiquitin-conjugating enzyme family.
CC       {ECO:0000255|PROSITE-ProRule:PRU00388}.
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DR   EMBL; D83004; BAA11675.1; -; mRNA.
DR   EMBL; BT006873; AAP35519.1; -; mRNA.
DR   EMBL; BC000396; AAH00396.1; -; mRNA.
DR   EMBL; BC003365; AAH03365.1; -; mRNA.
DR   EMBL; BC108704; AAI08705.1; -; mRNA.
DR   CCDS; CCDS31875.1; -.
DR   PIR; JC4894; JC4894.
DR   RefSeq; NP_003339.1; NM_003348.3.
DR   PDB; 1J7D; X-ray; 1.85 A; B=1-152.
DR   PDB; 2C2V; X-ray; 2.90 A; B/E/H/K=2-152.
DR   PDB; 3HCT; X-ray; 2.10 A; B=1-152.
DR   PDB; 3HCU; X-ray; 2.60 A; B/D=1-152.
DR   PDB; 3VON; X-ray; 3.15 A; C/E/G/J/L/N/Q/S/U/X/Z/b/e/g/i/l/n/p=3-150.
DR   PDB; 3W31; X-ray; 2.96 A; B=1-152.
DR   PDB; 4DHI; X-ray; 1.80 A; D=1-152.
DR   PDB; 4DHJ; X-ray; 2.35 A; C/G/K/N=1-152.
DR   PDB; 4DHZ; X-ray; 3.11 A; F=1-152.
DR   PDB; 4IP3; X-ray; 2.30 A; B=1-152.
DR   PDB; 4NR3; X-ray; 1.80 A; B=2-150.
DR   PDB; 4NRG; X-ray; 1.95 A; B=1-152.
DR   PDB; 4NRI; X-ray; 2.30 A; B=3-150.
DR   PDB; 4ONL; X-ray; 1.35 A; B=1-152.
DR   PDB; 4ONM; X-ray; 1.35 A; B=1-152.
DR   PDB; 4ONN; X-ray; 1.50 A; B=1-152.
DR   PDB; 4ORH; X-ray; 4.80 A; B/F/J=1-152.
DR   PDB; 4TKP; X-ray; 2.08 A; A=2-152.
DR   PDB; 4WHV; X-ray; 8.30 A; B/E/H/K=1-152.
DR   PDB; 5AIT; X-ray; 3.40 A; B/E=1-152.
DR   PDB; 5AIU; X-ray; 2.21 A; B/E=1-152.
DR   PDB; 5EYA; X-ray; 2.40 A; A/B=1-152.
DR   PDB; 5H7S; X-ray; 3.49 A; A/C=1-152.
DR   PDB; 5VNZ; X-ray; 3.41 A; B/E=1-152.
DR   PDB; 5VO0; X-ray; 3.90 A; B/E=1-152.
DR   PDB; 5YWR; X-ray; 1.47 A; A=1-152.
DR   PDB; 6D6I; X-ray; 2.55 A; B/E=3-152.
DR   PDB; 6JKY; X-ray; 2.45 A; B/E=1-152.
DR   PDB; 6KFP; X-ray; 2.92 A; B=1-152.
DR   PDB; 6KG6; X-ray; 2.39 A; G=1-152.
DR   PDB; 6KL4; X-ray; 2.85 A; B=1-152.
DR   PDB; 6LP2; X-ray; 2.48 A; D=1-152.
DR   PDB; 6P5B; X-ray; 2.10 A; C=1-152.
DR   PDB; 6S53; X-ray; 2.80 A; C/E/I/K=1-152.
DR   PDB; 6ULH; X-ray; 1.97 A; C=1-152.
DR   PDB; 6UMP; X-ray; 2.80 A; C=1-152.
DR   PDB; 6UMS; X-ray; 2.34 A; C=1-152.
DR   PDB; 7BXG; X-ray; 2.71 A; B=1-152.
DR   PDBsum; 1J7D; -.
DR   PDBsum; 2C2V; -.
DR   PDBsum; 3HCT; -.
DR   PDBsum; 3HCU; -.
DR   PDBsum; 3VON; -.
DR   PDBsum; 3W31; -.
DR   PDBsum; 4DHI; -.
DR   PDBsum; 4DHJ; -.
DR   PDBsum; 4DHZ; -.
DR   PDBsum; 4IP3; -.
DR   PDBsum; 4NR3; -.
DR   PDBsum; 4NRG; -.
DR   PDBsum; 4NRI; -.
DR   PDBsum; 4ONL; -.
DR   PDBsum; 4ONM; -.
DR   PDBsum; 4ONN; -.
DR   PDBsum; 4ORH; -.
DR   PDBsum; 4TKP; -.
DR   PDBsum; 4WHV; -.
DR   PDBsum; 5AIT; -.
DR   PDBsum; 5AIU; -.
DR   PDBsum; 5EYA; -.
DR   PDBsum; 5H7S; -.
DR   PDBsum; 5VNZ; -.
DR   PDBsum; 5VO0; -.
DR   PDBsum; 5YWR; -.
DR   PDBsum; 6D6I; -.
DR   PDBsum; 6JKY; -.
DR   PDBsum; 6KFP; -.
DR   PDBsum; 6KG6; -.
DR   PDBsum; 6KL4; -.
DR   PDBsum; 6LP2; -.
DR   PDBsum; 6P5B; -.
DR   PDBsum; 6S53; -.
DR   PDBsum; 6ULH; -.
DR   PDBsum; 6UMP; -.
DR   PDBsum; 6UMS; -.
DR   PDBsum; 7BXG; -.
DR   BMRB; P61088; -.
DR   SASBDB; P61088; -.
DR   SMR; P61088; -.
DR   BioGRID; 113182; 259.
DR   ComplexPortal; CPX-485; UBC13-UEV1A ubiquitin-conjugating enzyme E2 complex.
DR   ComplexPortal; CPX-530; UBC13-MMS2 ubiquitin-conjugating enzyme E2 complex.
DR   CORUM; P61088; -.
DR   DIP; DIP-29829N; -.
DR   IntAct; P61088; 143.
DR   MINT; P61088; -.
DR   STRING; 9606.ENSP00000316176; -.
DR   BindingDB; P61088; -.
DR   ChEMBL; CHEMBL6089; -.
DR   MoonDB; P61088; Predicted.
DR   iPTMnet; P61088; -.
DR   MetOSite; P61088; -.
DR   PhosphoSitePlus; P61088; -.
DR   SwissPalm; P61088; -.
DR   BioMuta; UBE2N; -.
DR   DMDM; 46577660; -.
DR   OGP; Q16781; -.
DR   REPRODUCTION-2DPAGE; IPI00003949; -.
DR   EPD; P61088; -.
DR   jPOST; P61088; -.
DR   MassIVE; P61088; -.
DR   PaxDb; P61088; -.
DR   PeptideAtlas; P61088; -.
DR   PRIDE; P61088; -.
DR   ProteomicsDB; 57264; -.
DR   TopDownProteomics; P61088; -.
DR   Antibodypedia; 1151; 368 antibodies.
DR   DNASU; 7334; -.
DR   Ensembl; ENST00000318066; ENSP00000316176; ENSG00000177889.
DR   GeneID; 7334; -.
DR   KEGG; hsa:7334; -.
DR   CTD; 7334; -.
DR   DisGeNET; 7334; -.
DR   GeneCards; UBE2N; -.
DR   HGNC; HGNC:12492; UBE2N.
DR   HPA; ENSG00000177889; Low tissue specificity.
DR   MIM; 603679; gene.
DR   neXtProt; NX_P61088; -.
DR   OpenTargets; ENSG00000177889; -.
DR   PharmGKB; PA37141; -.
DR   VEuPathDB; HostDB:ENSG00000177889.9; -.
DR   eggNOG; KOG0417; Eukaryota.
DR   GeneTree; ENSGT00540000070023; -.
DR   HOGENOM; CLU_030988_13_2_1; -.
DR   InParanoid; P61088; -.
DR   OMA; QWKVNES; -.
DR   OrthoDB; 1345547at2759; -.
DR   PhylomeDB; P61088; -.
DR   TreeFam; TF101126; -.
DR   BRENDA; 2.3.2.B6; 2681.
DR   PathwayCommons; P61088; -.
DR   Reactome; R-HSA-1169408; ISG15 antiviral mechanism.
DR   Reactome; R-HSA-168638; NOD1/2 Signaling Pathway.
DR   Reactome; R-HSA-168927; TICAM1, RIP1-mediated IKK complex recruitment.
DR   Reactome; R-HSA-202424; Downstream TCR signaling.
DR   Reactome; R-HSA-2871837; FCERI mediated NF-kB activation.
DR   Reactome; R-HSA-445989; TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
DR   Reactome; R-HSA-450302; activated TAK1 mediates p38 MAPK activation.
DR   Reactome; R-HSA-450321; JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
DR   Reactome; R-HSA-5607764; CLEC7A (Dectin-1) signaling.
DR   Reactome; R-HSA-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
DR   Reactome; R-HSA-5693571; Nonhomologous End-Joining (NHEJ).
DR   Reactome; R-HSA-5693607; Processing of DNA double-strand break ends.
DR   Reactome; R-HSA-5696395; Formation of Incision Complex in GG-NER.
DR   Reactome; R-HSA-69473; G2/M DNA damage checkpoint.
DR   Reactome; R-HSA-8866654; E3 ubiquitin ligases ubiquitinate target proteins.
DR   Reactome; R-HSA-9020702; Interleukin-1 signaling.
DR   Reactome; R-HSA-937039; IRAK1 recruits IKK complex.
DR   Reactome; R-HSA-937041; IKK complex recruitment mediated by RIP1.
DR   Reactome; R-HSA-9646399; Aggrephagy.
DR   Reactome; R-HSA-975110; TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling.
DR   Reactome; R-HSA-975144; IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation.
DR   Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR   SignaLink; P61088; -.
DR   SIGNOR; P61088; -.
DR   UniPathway; UPA00143; -.
DR   BioGRID-ORCS; 7334; 549 hits in 992 CRISPR screens.
DR   ChiTaRS; UBE2N; human.
DR   EvolutionaryTrace; P61088; -.
DR   GeneWiki; UBE2N; -.
DR   GenomeRNAi; 7334; -.
DR   Pharos; P61088; Tbio.
DR   PRO; PR:P61088; -.
DR   Proteomes; UP000005640; Chromosome 12.
DR   RNAct; P61088; protein.
DR   Bgee; ENSG00000177889; Expressed in right testis and 255 other tissues.
DR   ExpressionAtlas; P61088; baseline and differential.
DR   Genevisible; P61088; HS.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0001650; C:fibrillar center; IDA:HPA.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR   GO; GO:0032991; C:protein-containing complex; IDA:MGI.
DR   GO; GO:0031372; C:UBC13-MMS2 complex; IDA:HGNC-UCL.
DR   GO; GO:0035370; C:UBC13-UEV1A complex; IDA:UniProtKB.
DR   GO; GO:0000151; C:ubiquitin ligase complex; IDA:UniProtKB.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR   GO; GO:0043130; F:ubiquitin binding; IDA:HGNC-UCL.
DR   GO; GO:0061631; F:ubiquitin conjugating enzyme activity; ISS:UniProtKB.
DR   GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR   GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB.
DR   GO; GO:0000187; P:activation of MAPK activity; TAS:Reactome.
DR   GO; GO:0035973; P:aggrephagy; TAS:Reactome.
DR   GO; GO:0000729; P:DNA double-strand break processing; IMP:HGNC-UCL.
DR   GO; GO:0006302; P:double-strand break repair; TAS:Reactome.
DR   GO; GO:0000724; P:double-strand break repair via homologous recombination; IMP:HGNC-UCL.
DR   GO; GO:0006303; P:double-strand break repair via nonhomologous end joining; TAS:Reactome.
DR   GO; GO:0016574; P:histone ubiquitination; IMP:HGNC-UCL.
DR   GO; GO:0070498; P:interleukin-1-mediated signaling pathway; TAS:Reactome.
DR   GO; GO:0007254; P:JNK cascade; TAS:Reactome.
DR   GO; GO:0070423; P:nucleotide-binding oligomerization domain containing signaling pathway; TAS:Reactome.
DR   GO; GO:0045739; P:positive regulation of DNA repair; IMP:HGNC-UCL.
DR   GO; GO:0031058; P:positive regulation of histone modification; IMP:HGNC-UCL.
DR   GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IMP:HGNC-UCL.
DR   GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IMP:UniProtKB.
DR   GO; GO:0051443; P:positive regulation of ubiquitin-protein transferase activity; IMP:HGNC-UCL.
DR   GO; GO:0006301; P:postreplication repair; IMP:HGNC-UCL.
DR   GO; GO:0070534; P:protein K63-linked ubiquitination; IDA:UniProtKB.
DR   GO; GO:0000209; P:protein polyubiquitination; IBA:GO_Central.
DR   GO; GO:0016567; P:protein ubiquitination; IMP:HGNC-UCL.
DR   GO; GO:0006282; P:regulation of DNA repair; TAS:ProtInc.
DR   GO; GO:0033182; P:regulation of histone ubiquitination; IMP:HGNC-UCL.
DR   GO; GO:0050852; P:T cell receptor signaling pathway; IMP:UniProtKB.
DR   GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:Ensembl.
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   3D-structure; Acetylation; ATP-binding; Cytoplasm;
KW   Direct protein sequencing; Disulfide bond; DNA damage; DNA repair;
KW   Isopeptide bond; Nucleotide-binding; Nucleus; Reference proteome;
KW   Transferase; Ubl conjugation; Ubl conjugation pathway.
FT   CHAIN           1..152
FT                   /note="Ubiquitin-conjugating enzyme E2 N"
FT                   /id="PRO_0000082502"
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:0007744|PubMed:19608861"
FT   DISULFID        87
FT                   /note="Interchain (with C-78 in ISG15)"
FT                   /evidence="ECO:0000269|PubMed:22693631"
FT   CROSSLNK        92
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ISG15)"
FT                   /evidence="ECO:0000269|PubMed:16112642,
FT                   ECO:0000269|PubMed:16122702"
FT   MUTAGEN         87
FT                   /note="C->A: Loss of polyubiquitination of PCNA. Impairs
FT                   interaction with SHPRH."
FT                   /evidence="ECO:0000269|PubMed:17130289,
FT                   ECO:0000269|PubMed:17135271"
FT   MUTAGEN         92
FT                   /note="K->R: No ISGylation."
FT                   /evidence="ECO:0000269|PubMed:16112642,
FT                   ECO:0000269|PubMed:16122702"
FT   MUTAGEN         94
FT                   /note="K->R: No effect on ISGylation."
FT                   /evidence="ECO:0000269|PubMed:16112642"
FT   HELIX           6..17
FT                   /evidence="ECO:0007744|PDB:4ONL"
FT   STRAND          23..27
FT                   /evidence="ECO:0007744|PDB:4ONL"
FT   STRAND          29..31
FT                   /evidence="ECO:0007744|PDB:6KFP"
FT   STRAND          34..40
FT                   /evidence="ECO:0007744|PDB:4ONL"
FT   STRAND          43..45
FT                   /evidence="ECO:0007744|PDB:6UMP"
FT   TURN            46..49
FT                   /evidence="ECO:0007744|PDB:4ONL"
FT   STRAND          51..57
FT                   /evidence="ECO:0007744|PDB:4ONL"
FT   TURN            60..64
FT                   /evidence="ECO:0007744|PDB:4ONL"
FT   STRAND          68..71
FT                   /evidence="ECO:0007744|PDB:4ONL"
FT   STRAND          78..80
FT                   /evidence="ECO:0007744|PDB:5AIT"
FT   STRAND          84..86
FT                   /evidence="ECO:0007744|PDB:6KL4"
FT   HELIX           89..91
FT                   /evidence="ECO:0007744|PDB:4ONL"
FT   TURN            92..94
FT                   /evidence="ECO:0007744|PDB:4ONM"
FT   HELIX           101..113
FT                   /evidence="ECO:0007744|PDB:4ONL"
FT   STRAND          121..123
FT                   /evidence="ECO:0007744|PDB:4ONL"
FT   HELIX           124..131
FT                   /evidence="ECO:0007744|PDB:4ONL"
FT   HELIX           133..147
FT                   /evidence="ECO:0007744|PDB:4ONL"
FT   STRAND          148..150
FT                   /evidence="ECO:0007744|PDB:5YWR"
SQ   SEQUENCE   152 AA;  17138 MW;  FACD84D883D77407 CRC64;
     MAGLPRRIIK ETQRLLAEPV PGIKAEPDES NARYFHVVIA GPQDSPFEGG TFKLELFLPE
     EYPMAAPKVR FMTKIYHPNV DKLGRICLDI LKDKWSPALQ IRTVLLSIQA LLSAPNPDDP
     LANDVAEQWK TNEAQAIETA RAWTRLYAMN NI
//
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