Full text data of UBE2I
UBE2I
(UBC9, UBCE9)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
SUMO-conjugating enzyme UBC9; 6.3.2.- (SUMO-protein ligase; Ubiquitin carrier protein 9; Ubiquitin carrier protein I; Ubiquitin-conjugating enzyme E2 I; Ubiquitin-protein ligase I; p18)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
SUMO-conjugating enzyme UBC9; 6.3.2.- (SUMO-protein ligase; Ubiquitin carrier protein 9; Ubiquitin carrier protein I; Ubiquitin-conjugating enzyme E2 I; Ubiquitin-protein ligase I; p18)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00032957
IPI00032957 Ubiquitin-like protein SUMO-1 conjugati Ubiquitin-like protein SUMO-1 conjugati membrane n/a n/a n/a n/a n/a n/a n/a n/a 2 n/a n/a n/a n/a n/a n/a n/a n/a 2 n/a n/a intracellular n/a found at its expected molecular weight found at molecular weight
IPI00032957 Ubiquitin-like protein SUMO-1 conjugati Ubiquitin-like protein SUMO-1 conjugati membrane n/a n/a n/a n/a n/a n/a n/a n/a 2 n/a n/a n/a n/a n/a n/a n/a n/a 2 n/a n/a intracellular n/a found at its expected molecular weight found at molecular weight
UniProt
P63279
ID UBC9_HUMAN Reviewed; 158 AA.
AC P63279; D3DU69; P50550; Q15698; Q59GX1; Q86VB3;
DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 11-OCT-2004, sequence version 1.
DT 22-JAN-2014, entry version 119.
DE RecName: Full=SUMO-conjugating enzyme UBC9;
DE EC=6.3.2.-;
DE AltName: Full=SUMO-protein ligase;
DE AltName: Full=Ubiquitin carrier protein 9;
DE AltName: Full=Ubiquitin carrier protein I;
DE AltName: Full=Ubiquitin-conjugating enzyme E2 I;
DE AltName: Full=Ubiquitin-protein ligase I;
DE AltName: Full=p18;
GN Name=UBE2I; Synonyms=UBC9, UBCE9;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX PubMed=8668529; DOI=10.1093/nar/24.11.2005;
RA Yasugi T., Howley P.M.;
RT "Identification of the structural and functional human homolog of the
RT yeast ubiquitin conjugating enzyme UBC9.";
RL Nucleic Acids Res. 24:2005-2010(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9067428;
RA Tachibana M., Iwata N., Watanabe A., Nobukuni Y., Ploplis B.,
RA Kajigaya S.;
RT "Assignment of the gene for a ubiquitin-conjugating enzyme (UBE2I) to
RT human chromosome band 16p13.3 by in situ hybridization.";
RL Cytogenet. Cell Genet. 75:222-223(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Fetal brain;
RX PubMed=8565643;
RA Watanabe T.K., Fujiwara T., Kawai A., Shimizu F., Takami S.,
RA Hirano H., Okuno S., Ozaki K., Takeda S., Shimada Y., Nagata M.,
RA Takaichi A., Takahashi E., Nakamura Y., Shin S.;
RT "Cloning, expression, and mapping of UBE2I, a novel gene encoding a
RT human homologue of yeast ubiquitin-conjugating enzymes which are
RT critical for regulating the cell cycle.";
RL Cytogenet. Cell Genet. 72:86-89(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA], AND INTERACTION WITH PARP.
RX PubMed=9197546; DOI=10.1016/S0378-1119(97)00015-2;
RA Masson M., Menissier-de Murcia J., Mattei M.-G., de Murcia G.M.,
RA Niedergang C.P.;
RT "Poly(ADP-ribose) polymerase interacts with a novel human ubiquitin
RT conjugating enzyme: hUbc9.";
RL Gene 190:287-296(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=8610150; DOI=10.1073/pnas.93.7.2958;
RA Kovalenko O.V., Plug A.W., Haaf T., Gonda D.K., Ashley T., Ward D.C.,
RA Radding C.M., Golub E.I.;
RT "Mammalian ubiquitin-conjugating enzyme Ubc9 interacts with Rad51
RT recombination protein and localizes in synaptonemal complexes.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:2958-2963(1996).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8668125; DOI=10.1007/s004380050152;
RA Jiang W., Koltin Y.;
RT "Two-hybrid interaction of a human UBC9 homolog with centromere
RT proteins of Saccharomyces cerevisiae.";
RL Mol. Gen. Genet. 251:153-160(1996).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Placenta;
RX PubMed=8798754; DOI=10.1074/jbc.271.40.24418;
RA Wang Z.-Y., Qiu Q., Seufert W., Taguchi T., Testa J.R., Whitmore S.A.,
RA Callen D.F., Welsh D., Shenk T., Deuel T.F.;
RT "Molecular cloning of the cDNA and chromosome localization of the gene
RT for human ubiquitin-conjugating enzyme 9.";
RL J. Biol. Chem. 271:24811-24816(1996).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Shen Z.;
RL Submitted (OCT-1995) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9333025; DOI=10.1038/sj.onc.1201301;
RA Hahn S.L., Criqui-Filipe P., Wasylyk B.;
RT "Modulation of ETS-1 transcriptional activity by huUBC9, a ubiquitin-
RT conjugating enzyme.";
RL Oncogene 15:1489-1495(1997).
RN [10]
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
RT vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11157797; DOI=10.1093/hmg/10.4.339;
RA Daniels R.J., Peden J.F., Lloyd C., Horsley S.W., Clark K.,
RA Tufarelli C., Kearney L., Buckle V.J., Doggett N.A., Flint J.,
RA Higgs D.R.;
RT "Sequence, structure and pathology of the fully annotated terminal 2
RT Mb of the short arm of human chromosome 16.";
RL Hum. Mol. Genet. 10:339-352(2001).
RN [13]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [14]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X.,
RA Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A.,
RA Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.,
RA Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L.,
RA Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A.,
RA Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D.,
RA Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J.,
RA Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I.,
RA Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W.,
RA Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A.,
RA Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S.,
RA Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L.,
RA Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A.,
RA Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L.,
RA Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N.,
RA Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M.,
RA Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L.,
RA Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D.,
RA Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P.,
RA Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M.,
RA Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [15]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [16]
RP INTERACTION WITH ADENOVIRUS E1A.
RX PubMed=8824223; DOI=10.1074/jbc.271.42.25906;
RA Hateboer G., Hijmans E.M., Nooij J.B.D., Schlenker S., Jentsch S.,
RA Bernards R.;
RT "mUBC9, a novel adenovirus E1A-interacting protein that complements a
RT yeast cell cycle defect.";
RL J. Biol. Chem. 271:25906-25911(1996).
RN [17]
RP INTERACTION WITH SIAH1.
RX PubMed=9334332;
RA Hu G., Zhang S., Vidal M., Baer J.L., Xu T., Fearon E.R.;
RT "Mammalian homologs of seven in absentia regulate DCC via the
RT ubiquitin-proteasome pathway.";
RL Genes Dev. 11:2701-2714(1997).
RN [18]
RP INTERACTION WITH AR.
RX PubMed=10383460; DOI=10.1074/jbc.274.27.19441;
RA Poukka H., Aarnisalo P., Karvonen U., Palvimo J.J., Jaenne O.A.;
RT "Ubc9 interacts with the androgen receptor and activates receptor-
RT dependent transcription.";
RL J. Biol. Chem. 274:19441-19446(1999).
RN [19]
RP INTERACTION WITH FHIT.
RX PubMed=11085938; DOI=10.1042/0264-6021:3520443;
RA Shi Y., Zou M., Farid N.R., Paterson M.C.;
RT "Association of FHIT (fragile histidine triad), a candidate tumour
RT suppressor gene, with the ubiquitin-conjugating enzyme hUBC9.";
RL Biochem. J. 352:443-448(2000).
RN [20]
RP FUNCTION.
RX PubMed=11451954; DOI=10.1074/jbc.M104214200;
RA Tatham M.H., Jaffray E., Vaughan O.A., Desterro J.M.P., Botting C.H.,
RA Naismith J.H., Hay R.T.;
RT "Polymeric chains of SUMO-2 and SUMO-3 are conjugated to protein
RT substrates by SAE1/SAE2 and Ubc9.";
RL J. Biol. Chem. 276:35368-35374(2001).
RN [21]
RP INTERACTION WITH TFAP2A; TFAP2B AND TFAP2C.
RX PubMed=12072434; DOI=10.1074/jbc.M202780200;
RA Eloranta J.J., Hurst H.C.;
RT "Transcription factor AP-2 interacts with the SUMO-conjugating enzyme
RT UBC9 and is sumolated in vivo.";
RL J. Biol. Chem. 277:30798-30804(2002).
RN [22]
RP MUTAGENESIS OF 100-ASP-LYS-101.
RX PubMed=12641448; DOI=10.1021/bi026861x;
RA Tatham M.H., Chen Y., Hay R.T.;
RT "Role of two residues proximal to the active site of Ubc9 in substrate
RT recognition by the Ubc9.SUMO-1 thiolester complex.";
RL Biochemistry 42:3168-3179(2003).
RN [23]
RP INTERACTION WITH SUMO1; SUMO2; SUMO3 AND THE UBLE1A-UBLE1B E1 COMPLEX,
RP AND MUTAGENESIS OF 13-ARG-LYS-14 AND 17-ARG-LYS-18.
RX PubMed=12924945; DOI=10.1021/bi0345283;
RA Tatham M.H., Kim S., Yu B., Jaffray E., Song J., Zheng J.,
RA Rodriguez M.S., Hay R.T., Chen Y.;
RT "Role of an N-terminal site of Ubc9 in SUMO-1, -2, and -3 binding and
RT conjugation.";
RL Biochemistry 42:9959-9969(2003).
RN [24]
RP INTERACTION WITH RANBP2.
RX PubMed=15378033; DOI=10.1038/nsmb834;
RA Pichler A., Knipscheer P., Saitoh H., Sixma T.K., Melchior F.;
RT "The RanBP2 SUMO E3 ligase is neither HECT- nor RING-type.";
RL Nat. Struct. Mol. Biol. 11:984-991(2004).
RN [25]
RP INTERACTION WITH THE PML-RARALPHA ONCOPROTEIN, AND FUNCTION.
RX PubMed=15809060; DOI=10.1016/j.bbrc.2005.03.052;
RA Kim Y.E., Kim D.Y., Lee J.M., Kim S.T., Han T.H., Ahn J.H.;
RT "Requirement of the coiled-coil domain of PML-RARalpha oncoprotein for
RT localization, sumoylation, and inhibition of monocyte
RT differentiation.";
RL Biochem. Biophys. Res. Commun. 330:746-754(2005).
RN [26]
RP INTERACTION WITH RANBP2, AND MUTAGENESIS OF PHE-22; VAL-25; VAL-27;
RP GLU-42; LYS-48; GLU-54; LEU-57; LYS-59 AND ARG-61.
RX PubMed=15608651; DOI=10.1038/nsmb878;
RA Tatham M.H., Kim S., Jaffray E., Song J., Chen Y., Hay R.T.;
RT "Unique binding interactions among Ubc9, SUMO and RanBP2 reveal a
RT mechanism for SUMO paralog selection.";
RL Nat. Struct. Mol. Biol. 12:67-74(2005).
RN [27]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=16620772; DOI=10.1016/j.abb.2006.03.002;
RA Li T., Santockyte R., Shen R.-F., Tekle E., Wang G., Yang D.C.H.,
RA Chock P.B.;
RT "A general approach for investigating enzymatic pathways and
RT substrates for ubiquitin-like modifiers.";
RL Arch. Biochem. Biophys. 453:70-74(2006).
RN [28]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH SOX4.
RX PubMed=16631117; DOI=10.1016/j.bbrc.2006.03.194;
RA Pan X., Li H., Zhang P., Jin B., Man J., Tian L., Su G., Zhao J.,
RA Li W., Liu H., Gong W., Zhou T., Zhang X.;
RT "Ubc9 interacts with SOX4 and represses its transcriptional
RT activity.";
RL Biochem. Biophys. Res. Commun. 344:727-734(2006).
RN [29]
RP INTERACTION WITH HERPESVIRUS 6 IE2.
RX PubMed=17005699; DOI=10.1128/JVI.00375-06;
RA Tomoiu A., Gravel A., Tanguay R.M., Flamand L.;
RT "Functional interaction between human herpesvirus 6 immediate-early 2
RT protein and ubiquitin-conjugating enzyme 9 in the absence of
RT sumoylation.";
RL J. Virol. 80:10218-10228(2006).
RN [30]
RP INTERACTION WITH RWDD3.
RX PubMed=17956732; DOI=10.1016/j.cell.2007.07.044;
RA Carbia-Nagashima A., Gerez J., Perez-Castro C., Paez-Pereda M.,
RA Silberstein S., Stalla G.K., Holsboer F., Arzt E.;
RT "RSUME, a small RWD-containing protein, enhances SUMO conjugation and
RT stabilizes HIF-1alpha during hypoxia.";
RL Cell 131:309-323(2007).
RN [31]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION OF
RP KAT5-UBE2I-SENP6 COMPLEX.
RX PubMed=17704809; DOI=10.1038/sj.onc.1210710;
RA Cheng Z., Ke Y., Ding X., Wang F., Wang H., Wang W., Ahmed K., Liu Z.,
RA Xu Y., Aikhionbare F., Yan H., Liu J., Xue Y., Yu J., Powell M.,
RA Liang S., Wu Q., Reddy S.E., Hu R., Huang H., Jin C., Yao X.;
RT "Functional characterization of TIP60 sumoylation in UV-irradiated DNA
RT damage response.";
RL Oncogene 27:931-941(2008).
RN [32]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [33]
RP INTERACTION WITH DNMT1.
RX PubMed=19450230; DOI=10.1042/BJ20090142;
RA Lee B., Muller M.T.;
RT "SUMOylation enhances DNA methyltransferase 1 activity.";
RL Biochem. J. 421:449-461(2009).
RN [34]
RP INTERACTION WITH FOXL2, ROLE IN FOXL2 SUMOYLATION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=19744555; DOI=10.1016/j.cellsig.2009.09.001;
RA Kuo F.T., Bentsi-Barnes I.K., Barlow G.M., Bae J., Pisarska M.D.;
RT "Sumoylation of forkhead L2 by Ubc9 is required for its activity as a
RT transcriptional repressor of the Steroidogenic Acute Regulatory
RT gene.";
RL Cell. Signal. 21:1935-1944(2009).
RN [35]
RP INTERACTION WITH DNM1L, AND FUNCTION IN DNM1L SUMOYLATION.
RX PubMed=19638400; DOI=10.1096/fj.09-136630;
RA Figueroa-Romero C., Iniguez-Lluhi J.A., Stadler J., Chang C.R.,
RA Arnoult D., Keller P.J., Hong Y., Blackstone C., Feldman E.L.;
RT "SUMOylation of the mitochondrial fission protein Drp1 occurs at
RT multiple nonconsensus sites within the B domain and is linked to its
RT activity cycle.";
RL FASEB J. 23:3917-3927(2009).
RN [36]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-65, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., 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 [37]
RP INTERACTION WITH HUMAN ADENOVIRUS EARLY E1A PROTEIN.
RX PubMed=20543865; DOI=10.1038/onc.2010.226;
RA Yousef A.F., Fonseca G.J., Pelka P., Ablack J.N., Walsh C., Dick F.A.,
RA Bazett-Jones D.P., Shaw G.S., Mymryk J.S.;
RT "Identification of a molecular recognition feature in the E1A
RT oncoprotein that binds the SUMO conjugase UBC9 and likely interferes
RT with polySUMOylation.";
RL Oncogene 29:4693-4704(2010).
RN [38]
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.,
RA Buerckstuemmer T., 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 [39]
RP SUBCELLULAR LOCATION.
RX PubMed=22214662; DOI=10.4161/cc.11.2.18999;
RA Bennett R.L., Pan Y., Christian J., Hui T., May W.S. Jr.;
RT "The RAX/PACT-PKR stress response pathway promotes p53 sumoylation and
RT activation, leading to G(1) arrest.";
RL Cell Cycle 11:407-417(2012).
RN [40]
RP PHOSPHORYLATION AT SER-71.
RX PubMed=22509284; DOI=10.1371/journal.pone.0034250;
RA Su Y.F., Yang T., Huang H., Liu L.F., Hwang J.;
RT "Phosphorylation of Ubc9 by Cdk1 enhances SUMOylation activity.";
RL PLoS ONE 7:E34250-E34250(2012).
RN [41]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [42]
RP INTERACTION WITH UHRF2.
RX PubMed=23404503; DOI=10.1074/jbc.M112.438234;
RA Oh Y., Chung K.C.;
RT "UHRF2, a ubiquitin E3 ligase, acts as a small ubiquitin-like modifier
RT E3 ligase for zinc finger protein 131.";
RL J. Biol. Chem. 288:9102-9111(2013).
RN [43]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
RX PubMed=9261152; DOI=10.1074/jbc.272.34.21381;
RA Tong H., Hateboer G., Perrakis A., Bernards R., Sixma T.K.;
RT "Crystal structure of murine/human Ubc9 provides insight into the
RT variability of the ubiquitin-conjugating system.";
RL J. Biol. Chem. 272:21381-21387(1997).
RN [44]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH RANGAP1.
RX PubMed=11853669; DOI=10.1016/S0092-8674(02)00630-X;
RA Bernier-Villamor V., Sampson D.A., Matunis M.J., Lima C.D.;
RT "Structural basis for E2-mediated SUMO conjugation revealed by a
RT complex between ubiquitin-conjugating enzyme Ubc9 and RanGAP1.";
RL Cell 108:345-356(2002).
RN [45]
RP X-RAY CRYSTALLOGRAPHY (3.01 ANGSTROMS) IN COMPLEX WITH SUMO1; RANGAP1
RP AND RANBP2.
RX PubMed=15931224; DOI=10.1038/nature03588;
RA Reverter D., Lima C.D.;
RT "Insights into E3 ligase activity revealed by a SUMO-RanGAP1-Ubc9-
RT Nup358 complex.";
RL Nature 435:687-692(2005).
RN [46]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) IN COMPLEX WITH RANGAP1, AND
RP MUTAGENESIS OF ASN-85; TYR-87 AND ASP-127.
RX PubMed=16732283; DOI=10.1038/nsmb1104;
RA Yunus A.A., Lima C.D.;
RT "Lysine activation and functional analysis of E2-mediated conjugation
RT in the SUMO pathway.";
RL Nat. Struct. Mol. Biol. 13:491-499(2006).
RN [47]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEX WITH SUMO1,
RP INTERACTION WITH SUMO1; SUMO2 AND SUMO3, AND FUNCTION.
RX PubMed=17466333; DOI=10.1016/j.jmb.2007.04.006;
RA Capili A.D., Lima C.D.;
RT "Structure and analysis of a complex between SUMO and Ubc9 illustrates
RT features of a conserved E2-Ubl interaction.";
RL J. Mol. Biol. 369:608-618(2007).
RN [48]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) IN COMPLEX WITH NFATC2IP/NIP45,
RP INTERACTION WITH NFATC2IP, AND FUNCTION.
RX PubMed=20077568; DOI=10.1002/prot.22667;
RA Sekiyama N., Arita K., Ikeda Y., Hashiguchi K., Ariyoshi M.,
RA Tochio H., Saitoh H., Shirakawa M.;
RT "Structural basis for regulation of poly-SUMO chain by a SUMO-like
RT domain of Nip45.";
RL Proteins 78:1491-1502(2010).
RN [49]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) IN COMPLEX WITH IPO13.
RX PubMed=21139563; DOI=10.1038/emboj.2010.320;
RA Grunwald M., Bono F.;
RT "Structure of Importin13-Ubc9 complex: nuclear import and release of a
RT key regulator of sumoylation.";
RL EMBO J. 30:427-438(2011).
CC -!- FUNCTION: Accepts the ubiquitin-like proteins SUMO1, SUMO2, SUMO3
CC and SUMO4 from the UBLE1A-UBLE1B E1 complex and catalyzes their
CC covalent attachment to other proteins with the help of an E3
CC ligase such as RANBP2 or CBX4. Can catalyze the formation of poly-
CC SUMO chains. Necessary for sumoylation of FOXL2 and KAT5.
CC Essential for nuclear architecture and chromosome segregation.
CC Sumoylates p53/TP53 at 'Lys-386'.
CC -!- CATALYTIC ACTIVITY: ATP + SUMO + protein lysine = AMP +
CC diphosphate + protein N-SUMOyllysine.
CC -!- PATHWAY: Protein modification; protein sumoylation.
CC -!- SUBUNIT: Interacts with HIPK1, HIPK2, PPM1J, RASD2 and TCF3
CC Interacts with NR2C1; the interaction promotes its sumoylation (By
CC similarity). Forms a tight complex with RANGAP1 and RANBP2.
CC Interacts with SIAH1 and PARP. Interacts with various
CC transcription factors such as TFAP2A, TFAP2B, TFAP2C, AR, ETS1 and
CC SOX4. Interacts with RWDD3; the interaction enhances the
CC sumoylation of a number of proteins such as HIF1A and I-kappa-B.
CC Interacts with DNMT1. Interacts with FOXL2. Forms a complex with
CC SENP6 and UBE2I in response to UV irradiation. Interacts with
CC human herpesvirus 6 IE2. Interacts with human adenovirus early E1A
CC protein; this interaction interferes with polysumoylation
CC (Probable). Interacts with DNM1l (via its GTPase and B domains);
CC the interaction promotes sumoylation of DNM1L, mainly in its B
CC domain. Interacts with PML-RARA oncoprotein (via the coiled-colied
CC domain); the interaction is required for sumoylation of the PML-
CC RARA oncoprotein. Interacts with IPO13. Interacts with NFATC2IP;
CC this inhibits formation of poly-SUMO chains. Interacts with FHIT.
CC Interacts with PRKRA and p53/TP53 (By similarity). Interacts with
CC UHRF2.
CC -!- INTERACTION:
CC O14503:BHLHE40; NbExp=3; IntAct=EBI-80168, EBI-711810;
CC Q9UBC3:DNMT3B; NbExp=3; IntAct=EBI-80168, EBI-80125;
CC P03116:E1 (xeno); NbExp=2; IntAct=EBI-80168, EBI-7015985;
CC P19419:ELK1; NbExp=5; IntAct=EBI-80168, EBI-726632;
CC P56524:HDAC4; NbExp=3; IntAct=EBI-80168, EBI-308629;
CC Q9H2X6:HIPK2; NbExp=3; IntAct=EBI-80168, EBI-348345;
CC O94829:IPO13; NbExp=4; IntAct=EBI-80168, EBI-747310;
CC O75928:PIAS2; NbExp=5; IntAct=EBI-80168, EBI-348555;
CC P46060:RANGAP1; NbExp=4; IntAct=EBI-80168, EBI-396091;
CC Q9Y3V2:RWDD3; NbExp=5; IntAct=EBI-80168, EBI-1549885;
CC Q13485:SMAD4; NbExp=4; IntAct=EBI-80168, EBI-347263;
CC P56693:SOX10; NbExp=2; IntAct=EBI-80168, EBI-1167533;
CC P63165:SUMO1; NbExp=5; IntAct=EBI-80168, EBI-80140;
CC P61956:SUMO2; NbExp=6; IntAct=EBI-80168, EBI-473220;
CC Q92754:TFAP2C; NbExp=3; IntAct=EBI-80168, EBI-937309;
CC P22314:UBA1; NbExp=2; IntAct=EBI-80168, EBI-709688;
CC Q9Y4E5:ZNF451; NbExp=3; IntAct=EBI-80168, EBI-747230;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Mainly nuclear. In
CC spermatocytes, localizes in synaptonemal complexes. Recruited by
CC BCL11A into the nuclear body (By similarity).
CC -!- TISSUE SPECIFICITY: Expressed in heart, skeletal muscle, pancreas,
CC kidney, liver, lung, placenta and brain. Also expressed in testis
CC and thymus.
CC -!- PTM: Phosphorylation at Ser-71 significantly enhances SUMOylation
CC activity.
CC -!- SIMILARITY: Belongs to the ubiquitin-conjugating enzyme family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH51289.3; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC Sequence=BAD92225.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
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DR EMBL; X96427; CAA65287.1; -; mRNA.
DR EMBL; U45328; AAA86662.1; -; mRNA.
DR EMBL; D45050; BAA08091.1; -; mRNA.
DR EMBL; U29092; AAC51361.1; -; mRNA.
DR EMBL; U31933; AAB02181.1; -; mRNA.
DR EMBL; U31882; AAC50603.1; -; mRNA.
DR EMBL; U66867; AAC50716.1; -; mRNA.
DR EMBL; U66818; AAC50715.1; -; mRNA.
DR EMBL; U38785; AAB09410.1; -; mRNA.
DR EMBL; AJ002385; CAA05359.1; -; mRNA.
DR EMBL; BT006932; AAP35578.1; -; mRNA.
DR EMBL; AB208988; BAD92225.1; ALT_INIT; mRNA.
DR EMBL; AE006466; AAK61274.1; -; Genomic_DNA.
DR EMBL; AL031714; CAB45853.1; -; Genomic_DNA.
DR EMBL; CH471112; EAW85673.1; -; Genomic_DNA.
DR EMBL; CH471112; EAW85676.1; -; Genomic_DNA.
DR EMBL; CH471112; EAW85677.1; -; Genomic_DNA.
DR EMBL; CH471112; EAW85678.1; -; Genomic_DNA.
DR EMBL; CH471112; EAW85679.1; -; Genomic_DNA.
DR EMBL; BC000427; AAH00427.1; -; mRNA.
DR EMBL; BC004429; AAH04429.1; -; mRNA.
DR EMBL; BC051289; AAH51289.3; ALT_INIT; mRNA.
DR PIR; JC6056; JC6056.
DR RefSeq; NP_003336.1; NM_003345.4.
DR RefSeq; NP_919235.1; NM_194259.2.
DR RefSeq; NP_919236.1; NM_194260.2.
DR RefSeq; NP_919237.1; NM_194261.2.
DR RefSeq; XP_005255601.1; XM_005255544.1.
DR UniGene; Hs.302903; -.
DR PDB; 1A3S; X-ray; 2.80 A; A=1-158.
DR PDB; 1KPS; X-ray; 2.50 A; A/C=1-158.
DR PDB; 1Z5Q; Model; -; A=1-158.
DR PDB; 1Z5S; X-ray; 3.01 A; A=1-158.
DR PDB; 2GRN; X-ray; 1.80 A; A=1-158.
DR PDB; 2GRO; X-ray; 1.70 A; A=1-158.
DR PDB; 2GRP; X-ray; 2.05 A; A=1-158.
DR PDB; 2GRQ; X-ray; 1.70 A; A=1-158.
DR PDB; 2GRR; X-ray; 1.30 A; A=1-158.
DR PDB; 2O25; X-ray; 2.60 A; C/D=1-158.
DR PDB; 2PE6; X-ray; 2.40 A; A=1-158.
DR PDB; 2PX9; NMR; -; B=1-158.
DR PDB; 2XWU; X-ray; 2.80 A; A=1-158.
DR PDB; 3A4S; X-ray; 2.70 A; A/B=1-158.
DR PDB; 3UIN; X-ray; 2.60 A; A=1-158.
DR PDB; 3UIO; X-ray; 2.60 A; A=1-158.
DR PDB; 3UIP; X-ray; 2.29 A; A=1-158.
DR PDBsum; 1A3S; -.
DR PDBsum; 1KPS; -.
DR PDBsum; 1Z5Q; -.
DR PDBsum; 1Z5S; -.
DR PDBsum; 2GRN; -.
DR PDBsum; 2GRO; -.
DR PDBsum; 2GRP; -.
DR PDBsum; 2GRQ; -.
DR PDBsum; 2GRR; -.
DR PDBsum; 2O25; -.
DR PDBsum; 2PE6; -.
DR PDBsum; 2PX9; -.
DR PDBsum; 2XWU; -.
DR PDBsum; 3A4S; -.
DR PDBsum; 3UIN; -.
DR PDBsum; 3UIO; -.
DR PDBsum; 3UIP; -.
DR ProteinModelPortal; P63279; -.
DR SMR; P63279; 1-157.
DR DIP; DIP-29078N; -.
DR IntAct; P63279; 138.
DR MINT; MINT-137807; -.
DR STRING; 9606.ENSP00000324897; -.
DR BindingDB; P63279; -.
DR TCDB; 3.A.20.1.1; the peroxisomal protein importer (ppi) family.
DR PhosphoSite; P63279; -.
DR DMDM; 54039791; -.
DR PaxDb; P63279; -.
DR PeptideAtlas; P63279; -.
DR PRIDE; P63279; -.
DR DNASU; 7329; -.
DR Ensembl; ENST00000325437; ENSP00000324897; ENSG00000103275.
DR Ensembl; ENST00000355803; ENSP00000348056; ENSG00000103275.
DR Ensembl; ENST00000397514; ENSP00000380649; ENSG00000103275.
DR Ensembl; ENST00000397515; ENSP00000380650; ENSG00000103275.
DR Ensembl; ENST00000403747; ENSP00000385009; ENSG00000103275.
DR Ensembl; ENST00000406620; ENSP00000384568; ENSG00000103275.
DR Ensembl; ENST00000566587; ENSP00000457064; ENSG00000103275.
DR GeneID; 7329; -.
DR KEGG; hsa:7329; -.
DR UCSC; uc002clc.2; human.
DR CTD; 7329; -.
DR GeneCards; GC16P001359; -.
DR HGNC; HGNC:12485; UBE2I.
DR HPA; CAB009021; -.
DR HPA; HPA003909; -.
DR MIM; 601661; gene.
DR neXtProt; NX_P63279; -.
DR PharmGKB; PA37134; -.
DR eggNOG; COG5078; -.
DR HOGENOM; HOG000233454; -.
DR HOVERGEN; HBG063308; -.
DR KO; K10577; -.
DR OMA; WEGGVYK; -.
DR OrthoDB; EOG7B8S5F; -.
DR Reactome; REACT_111183; Meiosis.
DR Reactome; REACT_115566; Cell Cycle.
DR Reactome; REACT_17015; Metabolism of proteins.
DR SignaLink; P63279; -.
DR UniPathway; UPA00886; -.
DR ChiTaRS; UBE2I; human.
DR EvolutionaryTrace; P63279; -.
DR GeneWiki; UBE2I; -.
DR GenomeRNAi; 7329; -.
DR NextBio; 28682; -.
DR PRO; PR:P63279; -.
DR ArrayExpress; P63279; -.
DR Bgee; P63279; -.
DR CleanEx; HS_UBE2I; -.
DR Genevestigator; P63279; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0030425; C:dendrite; IEA:Ensembl.
DR GO; GO:0001650; C:fibrillar center; IEA:Ensembl.
DR GO; GO:0016605; C:PML body; IDA:UniProtKB.
DR GO; GO:0045202; C:synapse; IEA:Ensembl.
DR GO; GO:0000795; C:synaptonemal complex; TAS:ProtInc.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019789; F:SUMO ligase activity; IEA:Ensembl.
DR GO; GO:0004842; F:ubiquitin-protein ligase activity; TAS:BHF-UCL.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0007059; P:chromosome segregation; IEA:UniProtKB-KW.
DR GO; GO:0007067; P:mitosis; IEA:UniProtKB-KW.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IMP:BHF-UCL.
DR GO; GO:0033145; P:positive regulation of intracellular steroid hormone receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0051091; P:positive regulation of sequence-specific DNA binding transcription factor activity; IEA:Ensembl.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IEA:Ensembl.
DR GO; GO:0016925; P:protein sumoylation; IDA:BHF-UCL.
DR GO; GO:0010469; P:regulation of receptor activity; IEA:Ensembl.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; TAS:ProtInc.
DR Gene3D; 3.10.110.10; -; 1.
DR InterPro; IPR027230; Ubc9.
DR InterPro; IPR000608; UBQ-conjugat_E2.
DR InterPro; IPR023313; UBQ-conjugating_AS.
DR InterPro; IPR016135; UBQ-conjugating_enzyme/RWD.
DR PANTHER; PTHR24067:SF51; PTHR24067:SF51; 1.
DR Pfam; PF00179; UQ_con; 1.
DR SUPFAM; SSF54495; SSF54495; 1.
DR PROSITE; PS00183; UBIQUITIN_CONJUGAT_1; 1.
DR PROSITE; PS50127; UBIQUITIN_CONJUGAT_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; ATP-binding; Cell cycle; Cell division;
KW Chromosome partition; Complete proteome; Cytoplasm;
KW Host-virus interaction; Isopeptide bond; Ligase; Mitosis;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Ubl conjugation; Ubl conjugation pathway.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 158 SUMO-conjugating enzyme UBC9.
FT /FTId=PRO_0000082454.
FT REGION 13 18 Interaction with SUMO1.
FT ACT_SITE 93 93 Glycyl thioester intermediate.
FT SITE 4 4 Interaction with RANBP2.
FT SITE 25 25 Interaction with RANBP2.
FT SITE 57 57 Interaction with RANBP2.
FT SITE 100 101 Substrate binding.
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 65 65 N6-acetyllysine.
FT MOD_RES 71 71 Phosphoserine; by CDK1.
FT CROSSLNK 18 18 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ubiquitin).
FT MUTAGEN 13 14 RK->AA: Impairs binding to SUMO1 and
FT catalytic activity.
FT MUTAGEN 17 18 RK->AA: Impairs binding to SUMO1 and
FT catalytic activity.
FT MUTAGEN 22 22 F->A: Impairs binding to RANBP2.
FT MUTAGEN 25 25 V->A: Impairs binding to RANBP2.
FT MUTAGEN 27 27 V->A: Impairs binding to RANBP2.
FT MUTAGEN 42 42 E->A: Slightly impairs binding to RANBP2.
FT MUTAGEN 48 48 K->A: Slightly impairs binding to RANBP2.
FT MUTAGEN 54 54 E->A: Slightly impairs binding to RANBP2.
FT MUTAGEN 57 57 L->A: Impairs binding to RANBP2.
FT MUTAGEN 59 59 K->A: Impairs binding to RANBP2.
FT MUTAGEN 61 61 R->A: Slightly impairs binding to RANBP2.
FT MUTAGEN 85 85 N->Q: Impairs catalytic activity.
FT MUTAGEN 87 87 Y->A: Impairs catalytic activity.
FT MUTAGEN 93 93 C->S: Loss of enhancement of sumoylation
FT by RWDD3. No effect on RWDD3 protein
FT levels.
FT MUTAGEN 100 101 DK->AA: Impairs catalytic activity.
FT MUTAGEN 127 127 D->A: Impairs catalytic activity.
FT MUTAGEN 127 127 D->S: No effect on catalytic activity.
FT CONFLICT 18 18 K -> P (in Ref. 6; AAC50603).
FT CONFLICT 86 89 VYPS -> GVPF (in Ref. 6; AAC50603).
FT HELIX 3 18
FT STRAND 25 30
FT STRAND 32 34
FT STRAND 36 46
FT TURN 52 55
FT STRAND 57 63
FT TURN 66 69
FT STRAND 74 79
FT STRAND 90 92
FT HELIX 95 97
FT TURN 99 102
FT HELIX 109 121
FT HELIX 131 139
FT HELIX 141 154
SQ SEQUENCE 158 AA; 18007 MW; E2C826E9C8D0683D CRC64;
MSGIALSRLA QERKAWRKDH PFGFVAVPTK NPDGTMNLMN WECAIPGKKG TPWEGGLFKL
RMLFKDDYPS SPPKCKFEPP LFHPNVYPSG TVCLSILEED KDWRPAITIK QILLGIQELL
NEPNIQDPAQ AEAYTIYCQN RVEYEKRVRA QAKKFAPS
//
ID UBC9_HUMAN Reviewed; 158 AA.
AC P63279; D3DU69; P50550; Q15698; Q59GX1; Q86VB3;
DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 11-OCT-2004, sequence version 1.
DT 22-JAN-2014, entry version 119.
DE RecName: Full=SUMO-conjugating enzyme UBC9;
DE EC=6.3.2.-;
DE AltName: Full=SUMO-protein ligase;
DE AltName: Full=Ubiquitin carrier protein 9;
DE AltName: Full=Ubiquitin carrier protein I;
DE AltName: Full=Ubiquitin-conjugating enzyme E2 I;
DE AltName: Full=Ubiquitin-protein ligase I;
DE AltName: Full=p18;
GN Name=UBE2I; Synonyms=UBC9, UBCE9;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX PubMed=8668529; DOI=10.1093/nar/24.11.2005;
RA Yasugi T., Howley P.M.;
RT "Identification of the structural and functional human homolog of the
RT yeast ubiquitin conjugating enzyme UBC9.";
RL Nucleic Acids Res. 24:2005-2010(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9067428;
RA Tachibana M., Iwata N., Watanabe A., Nobukuni Y., Ploplis B.,
RA Kajigaya S.;
RT "Assignment of the gene for a ubiquitin-conjugating enzyme (UBE2I) to
RT human chromosome band 16p13.3 by in situ hybridization.";
RL Cytogenet. Cell Genet. 75:222-223(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Fetal brain;
RX PubMed=8565643;
RA Watanabe T.K., Fujiwara T., Kawai A., Shimizu F., Takami S.,
RA Hirano H., Okuno S., Ozaki K., Takeda S., Shimada Y., Nagata M.,
RA Takaichi A., Takahashi E., Nakamura Y., Shin S.;
RT "Cloning, expression, and mapping of UBE2I, a novel gene encoding a
RT human homologue of yeast ubiquitin-conjugating enzymes which are
RT critical for regulating the cell cycle.";
RL Cytogenet. Cell Genet. 72:86-89(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA], AND INTERACTION WITH PARP.
RX PubMed=9197546; DOI=10.1016/S0378-1119(97)00015-2;
RA Masson M., Menissier-de Murcia J., Mattei M.-G., de Murcia G.M.,
RA Niedergang C.P.;
RT "Poly(ADP-ribose) polymerase interacts with a novel human ubiquitin
RT conjugating enzyme: hUbc9.";
RL Gene 190:287-296(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=8610150; DOI=10.1073/pnas.93.7.2958;
RA Kovalenko O.V., Plug A.W., Haaf T., Gonda D.K., Ashley T., Ward D.C.,
RA Radding C.M., Golub E.I.;
RT "Mammalian ubiquitin-conjugating enzyme Ubc9 interacts with Rad51
RT recombination protein and localizes in synaptonemal complexes.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:2958-2963(1996).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8668125; DOI=10.1007/s004380050152;
RA Jiang W., Koltin Y.;
RT "Two-hybrid interaction of a human UBC9 homolog with centromere
RT proteins of Saccharomyces cerevisiae.";
RL Mol. Gen. Genet. 251:153-160(1996).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Placenta;
RX PubMed=8798754; DOI=10.1074/jbc.271.40.24418;
RA Wang Z.-Y., Qiu Q., Seufert W., Taguchi T., Testa J.R., Whitmore S.A.,
RA Callen D.F., Welsh D., Shenk T., Deuel T.F.;
RT "Molecular cloning of the cDNA and chromosome localization of the gene
RT for human ubiquitin-conjugating enzyme 9.";
RL J. Biol. Chem. 271:24811-24816(1996).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Shen Z.;
RL Submitted (OCT-1995) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9333025; DOI=10.1038/sj.onc.1201301;
RA Hahn S.L., Criqui-Filipe P., Wasylyk B.;
RT "Modulation of ETS-1 transcriptional activity by huUBC9, a ubiquitin-
RT conjugating enzyme.";
RL Oncogene 15:1489-1495(1997).
RN [10]
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
RT vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11157797; DOI=10.1093/hmg/10.4.339;
RA Daniels R.J., Peden J.F., Lloyd C., Horsley S.W., Clark K.,
RA Tufarelli C., Kearney L., Buckle V.J., Doggett N.A., Flint J.,
RA Higgs D.R.;
RT "Sequence, structure and pathology of the fully annotated terminal 2
RT Mb of the short arm of human chromosome 16.";
RL Hum. Mol. Genet. 10:339-352(2001).
RN [13]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [14]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X.,
RA Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A.,
RA Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.,
RA Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L.,
RA Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A.,
RA Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D.,
RA Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J.,
RA Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I.,
RA Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W.,
RA Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A.,
RA Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S.,
RA Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L.,
RA Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A.,
RA Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L.,
RA Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N.,
RA Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M.,
RA Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L.,
RA Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D.,
RA Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P.,
RA Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M.,
RA Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [15]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [16]
RP INTERACTION WITH ADENOVIRUS E1A.
RX PubMed=8824223; DOI=10.1074/jbc.271.42.25906;
RA Hateboer G., Hijmans E.M., Nooij J.B.D., Schlenker S., Jentsch S.,
RA Bernards R.;
RT "mUBC9, a novel adenovirus E1A-interacting protein that complements a
RT yeast cell cycle defect.";
RL J. Biol. Chem. 271:25906-25911(1996).
RN [17]
RP INTERACTION WITH SIAH1.
RX PubMed=9334332;
RA Hu G., Zhang S., Vidal M., Baer J.L., Xu T., Fearon E.R.;
RT "Mammalian homologs of seven in absentia regulate DCC via the
RT ubiquitin-proteasome pathway.";
RL Genes Dev. 11:2701-2714(1997).
RN [18]
RP INTERACTION WITH AR.
RX PubMed=10383460; DOI=10.1074/jbc.274.27.19441;
RA Poukka H., Aarnisalo P., Karvonen U., Palvimo J.J., Jaenne O.A.;
RT "Ubc9 interacts with the androgen receptor and activates receptor-
RT dependent transcription.";
RL J. Biol. Chem. 274:19441-19446(1999).
RN [19]
RP INTERACTION WITH FHIT.
RX PubMed=11085938; DOI=10.1042/0264-6021:3520443;
RA Shi Y., Zou M., Farid N.R., Paterson M.C.;
RT "Association of FHIT (fragile histidine triad), a candidate tumour
RT suppressor gene, with the ubiquitin-conjugating enzyme hUBC9.";
RL Biochem. J. 352:443-448(2000).
RN [20]
RP FUNCTION.
RX PubMed=11451954; DOI=10.1074/jbc.M104214200;
RA Tatham M.H., Jaffray E., Vaughan O.A., Desterro J.M.P., Botting C.H.,
RA Naismith J.H., Hay R.T.;
RT "Polymeric chains of SUMO-2 and SUMO-3 are conjugated to protein
RT substrates by SAE1/SAE2 and Ubc9.";
RL J. Biol. Chem. 276:35368-35374(2001).
RN [21]
RP INTERACTION WITH TFAP2A; TFAP2B AND TFAP2C.
RX PubMed=12072434; DOI=10.1074/jbc.M202780200;
RA Eloranta J.J., Hurst H.C.;
RT "Transcription factor AP-2 interacts with the SUMO-conjugating enzyme
RT UBC9 and is sumolated in vivo.";
RL J. Biol. Chem. 277:30798-30804(2002).
RN [22]
RP MUTAGENESIS OF 100-ASP-LYS-101.
RX PubMed=12641448; DOI=10.1021/bi026861x;
RA Tatham M.H., Chen Y., Hay R.T.;
RT "Role of two residues proximal to the active site of Ubc9 in substrate
RT recognition by the Ubc9.SUMO-1 thiolester complex.";
RL Biochemistry 42:3168-3179(2003).
RN [23]
RP INTERACTION WITH SUMO1; SUMO2; SUMO3 AND THE UBLE1A-UBLE1B E1 COMPLEX,
RP AND MUTAGENESIS OF 13-ARG-LYS-14 AND 17-ARG-LYS-18.
RX PubMed=12924945; DOI=10.1021/bi0345283;
RA Tatham M.H., Kim S., Yu B., Jaffray E., Song J., Zheng J.,
RA Rodriguez M.S., Hay R.T., Chen Y.;
RT "Role of an N-terminal site of Ubc9 in SUMO-1, -2, and -3 binding and
RT conjugation.";
RL Biochemistry 42:9959-9969(2003).
RN [24]
RP INTERACTION WITH RANBP2.
RX PubMed=15378033; DOI=10.1038/nsmb834;
RA Pichler A., Knipscheer P., Saitoh H., Sixma T.K., Melchior F.;
RT "The RanBP2 SUMO E3 ligase is neither HECT- nor RING-type.";
RL Nat. Struct. Mol. Biol. 11:984-991(2004).
RN [25]
RP INTERACTION WITH THE PML-RARALPHA ONCOPROTEIN, AND FUNCTION.
RX PubMed=15809060; DOI=10.1016/j.bbrc.2005.03.052;
RA Kim Y.E., Kim D.Y., Lee J.M., Kim S.T., Han T.H., Ahn J.H.;
RT "Requirement of the coiled-coil domain of PML-RARalpha oncoprotein for
RT localization, sumoylation, and inhibition of monocyte
RT differentiation.";
RL Biochem. Biophys. Res. Commun. 330:746-754(2005).
RN [26]
RP INTERACTION WITH RANBP2, AND MUTAGENESIS OF PHE-22; VAL-25; VAL-27;
RP GLU-42; LYS-48; GLU-54; LEU-57; LYS-59 AND ARG-61.
RX PubMed=15608651; DOI=10.1038/nsmb878;
RA Tatham M.H., Kim S., Jaffray E., Song J., Chen Y., Hay R.T.;
RT "Unique binding interactions among Ubc9, SUMO and RanBP2 reveal a
RT mechanism for SUMO paralog selection.";
RL Nat. Struct. Mol. Biol. 12:67-74(2005).
RN [27]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=16620772; DOI=10.1016/j.abb.2006.03.002;
RA Li T., Santockyte R., Shen R.-F., Tekle E., Wang G., Yang D.C.H.,
RA Chock P.B.;
RT "A general approach for investigating enzymatic pathways and
RT substrates for ubiquitin-like modifiers.";
RL Arch. Biochem. Biophys. 453:70-74(2006).
RN [28]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH SOX4.
RX PubMed=16631117; DOI=10.1016/j.bbrc.2006.03.194;
RA Pan X., Li H., Zhang P., Jin B., Man J., Tian L., Su G., Zhao J.,
RA Li W., Liu H., Gong W., Zhou T., Zhang X.;
RT "Ubc9 interacts with SOX4 and represses its transcriptional
RT activity.";
RL Biochem. Biophys. Res. Commun. 344:727-734(2006).
RN [29]
RP INTERACTION WITH HERPESVIRUS 6 IE2.
RX PubMed=17005699; DOI=10.1128/JVI.00375-06;
RA Tomoiu A., Gravel A., Tanguay R.M., Flamand L.;
RT "Functional interaction between human herpesvirus 6 immediate-early 2
RT protein and ubiquitin-conjugating enzyme 9 in the absence of
RT sumoylation.";
RL J. Virol. 80:10218-10228(2006).
RN [30]
RP INTERACTION WITH RWDD3.
RX PubMed=17956732; DOI=10.1016/j.cell.2007.07.044;
RA Carbia-Nagashima A., Gerez J., Perez-Castro C., Paez-Pereda M.,
RA Silberstein S., Stalla G.K., Holsboer F., Arzt E.;
RT "RSUME, a small RWD-containing protein, enhances SUMO conjugation and
RT stabilizes HIF-1alpha during hypoxia.";
RL Cell 131:309-323(2007).
RN [31]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION OF
RP KAT5-UBE2I-SENP6 COMPLEX.
RX PubMed=17704809; DOI=10.1038/sj.onc.1210710;
RA Cheng Z., Ke Y., Ding X., Wang F., Wang H., Wang W., Ahmed K., Liu Z.,
RA Xu Y., Aikhionbare F., Yan H., Liu J., Xue Y., Yu J., Powell M.,
RA Liang S., Wu Q., Reddy S.E., Hu R., Huang H., Jin C., Yao X.;
RT "Functional characterization of TIP60 sumoylation in UV-irradiated DNA
RT damage response.";
RL Oncogene 27:931-941(2008).
RN [32]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [33]
RP INTERACTION WITH DNMT1.
RX PubMed=19450230; DOI=10.1042/BJ20090142;
RA Lee B., Muller M.T.;
RT "SUMOylation enhances DNA methyltransferase 1 activity.";
RL Biochem. J. 421:449-461(2009).
RN [34]
RP INTERACTION WITH FOXL2, ROLE IN FOXL2 SUMOYLATION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=19744555; DOI=10.1016/j.cellsig.2009.09.001;
RA Kuo F.T., Bentsi-Barnes I.K., Barlow G.M., Bae J., Pisarska M.D.;
RT "Sumoylation of forkhead L2 by Ubc9 is required for its activity as a
RT transcriptional repressor of the Steroidogenic Acute Regulatory
RT gene.";
RL Cell. Signal. 21:1935-1944(2009).
RN [35]
RP INTERACTION WITH DNM1L, AND FUNCTION IN DNM1L SUMOYLATION.
RX PubMed=19638400; DOI=10.1096/fj.09-136630;
RA Figueroa-Romero C., Iniguez-Lluhi J.A., Stadler J., Chang C.R.,
RA Arnoult D., Keller P.J., Hong Y., Blackstone C., Feldman E.L.;
RT "SUMOylation of the mitochondrial fission protein Drp1 occurs at
RT multiple nonconsensus sites within the B domain and is linked to its
RT activity cycle.";
RL FASEB J. 23:3917-3927(2009).
RN [36]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-65, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., 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 [37]
RP INTERACTION WITH HUMAN ADENOVIRUS EARLY E1A PROTEIN.
RX PubMed=20543865; DOI=10.1038/onc.2010.226;
RA Yousef A.F., Fonseca G.J., Pelka P., Ablack J.N., Walsh C., Dick F.A.,
RA Bazett-Jones D.P., Shaw G.S., Mymryk J.S.;
RT "Identification of a molecular recognition feature in the E1A
RT oncoprotein that binds the SUMO conjugase UBC9 and likely interferes
RT with polySUMOylation.";
RL Oncogene 29:4693-4704(2010).
RN [38]
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.,
RA Buerckstuemmer T., 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 [39]
RP SUBCELLULAR LOCATION.
RX PubMed=22214662; DOI=10.4161/cc.11.2.18999;
RA Bennett R.L., Pan Y., Christian J., Hui T., May W.S. Jr.;
RT "The RAX/PACT-PKR stress response pathway promotes p53 sumoylation and
RT activation, leading to G(1) arrest.";
RL Cell Cycle 11:407-417(2012).
RN [40]
RP PHOSPHORYLATION AT SER-71.
RX PubMed=22509284; DOI=10.1371/journal.pone.0034250;
RA Su Y.F., Yang T., Huang H., Liu L.F., Hwang J.;
RT "Phosphorylation of Ubc9 by Cdk1 enhances SUMOylation activity.";
RL PLoS ONE 7:E34250-E34250(2012).
RN [41]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [42]
RP INTERACTION WITH UHRF2.
RX PubMed=23404503; DOI=10.1074/jbc.M112.438234;
RA Oh Y., Chung K.C.;
RT "UHRF2, a ubiquitin E3 ligase, acts as a small ubiquitin-like modifier
RT E3 ligase for zinc finger protein 131.";
RL J. Biol. Chem. 288:9102-9111(2013).
RN [43]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
RX PubMed=9261152; DOI=10.1074/jbc.272.34.21381;
RA Tong H., Hateboer G., Perrakis A., Bernards R., Sixma T.K.;
RT "Crystal structure of murine/human Ubc9 provides insight into the
RT variability of the ubiquitin-conjugating system.";
RL J. Biol. Chem. 272:21381-21387(1997).
RN [44]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH RANGAP1.
RX PubMed=11853669; DOI=10.1016/S0092-8674(02)00630-X;
RA Bernier-Villamor V., Sampson D.A., Matunis M.J., Lima C.D.;
RT "Structural basis for E2-mediated SUMO conjugation revealed by a
RT complex between ubiquitin-conjugating enzyme Ubc9 and RanGAP1.";
RL Cell 108:345-356(2002).
RN [45]
RP X-RAY CRYSTALLOGRAPHY (3.01 ANGSTROMS) IN COMPLEX WITH SUMO1; RANGAP1
RP AND RANBP2.
RX PubMed=15931224; DOI=10.1038/nature03588;
RA Reverter D., Lima C.D.;
RT "Insights into E3 ligase activity revealed by a SUMO-RanGAP1-Ubc9-
RT Nup358 complex.";
RL Nature 435:687-692(2005).
RN [46]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) IN COMPLEX WITH RANGAP1, AND
RP MUTAGENESIS OF ASN-85; TYR-87 AND ASP-127.
RX PubMed=16732283; DOI=10.1038/nsmb1104;
RA Yunus A.A., Lima C.D.;
RT "Lysine activation and functional analysis of E2-mediated conjugation
RT in the SUMO pathway.";
RL Nat. Struct. Mol. Biol. 13:491-499(2006).
RN [47]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEX WITH SUMO1,
RP INTERACTION WITH SUMO1; SUMO2 AND SUMO3, AND FUNCTION.
RX PubMed=17466333; DOI=10.1016/j.jmb.2007.04.006;
RA Capili A.D., Lima C.D.;
RT "Structure and analysis of a complex between SUMO and Ubc9 illustrates
RT features of a conserved E2-Ubl interaction.";
RL J. Mol. Biol. 369:608-618(2007).
RN [48]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) IN COMPLEX WITH NFATC2IP/NIP45,
RP INTERACTION WITH NFATC2IP, AND FUNCTION.
RX PubMed=20077568; DOI=10.1002/prot.22667;
RA Sekiyama N., Arita K., Ikeda Y., Hashiguchi K., Ariyoshi M.,
RA Tochio H., Saitoh H., Shirakawa M.;
RT "Structural basis for regulation of poly-SUMO chain by a SUMO-like
RT domain of Nip45.";
RL Proteins 78:1491-1502(2010).
RN [49]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) IN COMPLEX WITH IPO13.
RX PubMed=21139563; DOI=10.1038/emboj.2010.320;
RA Grunwald M., Bono F.;
RT "Structure of Importin13-Ubc9 complex: nuclear import and release of a
RT key regulator of sumoylation.";
RL EMBO J. 30:427-438(2011).
CC -!- FUNCTION: Accepts the ubiquitin-like proteins SUMO1, SUMO2, SUMO3
CC and SUMO4 from the UBLE1A-UBLE1B E1 complex and catalyzes their
CC covalent attachment to other proteins with the help of an E3
CC ligase such as RANBP2 or CBX4. Can catalyze the formation of poly-
CC SUMO chains. Necessary for sumoylation of FOXL2 and KAT5.
CC Essential for nuclear architecture and chromosome segregation.
CC Sumoylates p53/TP53 at 'Lys-386'.
CC -!- CATALYTIC ACTIVITY: ATP + SUMO + protein lysine = AMP +
CC diphosphate + protein N-SUMOyllysine.
CC -!- PATHWAY: Protein modification; protein sumoylation.
CC -!- SUBUNIT: Interacts with HIPK1, HIPK2, PPM1J, RASD2 and TCF3
CC Interacts with NR2C1; the interaction promotes its sumoylation (By
CC similarity). Forms a tight complex with RANGAP1 and RANBP2.
CC Interacts with SIAH1 and PARP. Interacts with various
CC transcription factors such as TFAP2A, TFAP2B, TFAP2C, AR, ETS1 and
CC SOX4. Interacts with RWDD3; the interaction enhances the
CC sumoylation of a number of proteins such as HIF1A and I-kappa-B.
CC Interacts with DNMT1. Interacts with FOXL2. Forms a complex with
CC SENP6 and UBE2I in response to UV irradiation. Interacts with
CC human herpesvirus 6 IE2. Interacts with human adenovirus early E1A
CC protein; this interaction interferes with polysumoylation
CC (Probable). Interacts with DNM1l (via its GTPase and B domains);
CC the interaction promotes sumoylation of DNM1L, mainly in its B
CC domain. Interacts with PML-RARA oncoprotein (via the coiled-colied
CC domain); the interaction is required for sumoylation of the PML-
CC RARA oncoprotein. Interacts with IPO13. Interacts with NFATC2IP;
CC this inhibits formation of poly-SUMO chains. Interacts with FHIT.
CC Interacts with PRKRA and p53/TP53 (By similarity). Interacts with
CC UHRF2.
CC -!- INTERACTION:
CC O14503:BHLHE40; NbExp=3; IntAct=EBI-80168, EBI-711810;
CC Q9UBC3:DNMT3B; NbExp=3; IntAct=EBI-80168, EBI-80125;
CC P03116:E1 (xeno); NbExp=2; IntAct=EBI-80168, EBI-7015985;
CC P19419:ELK1; NbExp=5; IntAct=EBI-80168, EBI-726632;
CC P56524:HDAC4; NbExp=3; IntAct=EBI-80168, EBI-308629;
CC Q9H2X6:HIPK2; NbExp=3; IntAct=EBI-80168, EBI-348345;
CC O94829:IPO13; NbExp=4; IntAct=EBI-80168, EBI-747310;
CC O75928:PIAS2; NbExp=5; IntAct=EBI-80168, EBI-348555;
CC P46060:RANGAP1; NbExp=4; IntAct=EBI-80168, EBI-396091;
CC Q9Y3V2:RWDD3; NbExp=5; IntAct=EBI-80168, EBI-1549885;
CC Q13485:SMAD4; NbExp=4; IntAct=EBI-80168, EBI-347263;
CC P56693:SOX10; NbExp=2; IntAct=EBI-80168, EBI-1167533;
CC P63165:SUMO1; NbExp=5; IntAct=EBI-80168, EBI-80140;
CC P61956:SUMO2; NbExp=6; IntAct=EBI-80168, EBI-473220;
CC Q92754:TFAP2C; NbExp=3; IntAct=EBI-80168, EBI-937309;
CC P22314:UBA1; NbExp=2; IntAct=EBI-80168, EBI-709688;
CC Q9Y4E5:ZNF451; NbExp=3; IntAct=EBI-80168, EBI-747230;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Mainly nuclear. In
CC spermatocytes, localizes in synaptonemal complexes. Recruited by
CC BCL11A into the nuclear body (By similarity).
CC -!- TISSUE SPECIFICITY: Expressed in heart, skeletal muscle, pancreas,
CC kidney, liver, lung, placenta and brain. Also expressed in testis
CC and thymus.
CC -!- PTM: Phosphorylation at Ser-71 significantly enhances SUMOylation
CC activity.
CC -!- SIMILARITY: Belongs to the ubiquitin-conjugating enzyme family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH51289.3; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC Sequence=BAD92225.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
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DR EMBL; X96427; CAA65287.1; -; mRNA.
DR EMBL; U45328; AAA86662.1; -; mRNA.
DR EMBL; D45050; BAA08091.1; -; mRNA.
DR EMBL; U29092; AAC51361.1; -; mRNA.
DR EMBL; U31933; AAB02181.1; -; mRNA.
DR EMBL; U31882; AAC50603.1; -; mRNA.
DR EMBL; U66867; AAC50716.1; -; mRNA.
DR EMBL; U66818; AAC50715.1; -; mRNA.
DR EMBL; U38785; AAB09410.1; -; mRNA.
DR EMBL; AJ002385; CAA05359.1; -; mRNA.
DR EMBL; BT006932; AAP35578.1; -; mRNA.
DR EMBL; AB208988; BAD92225.1; ALT_INIT; mRNA.
DR EMBL; AE006466; AAK61274.1; -; Genomic_DNA.
DR EMBL; AL031714; CAB45853.1; -; Genomic_DNA.
DR EMBL; CH471112; EAW85673.1; -; Genomic_DNA.
DR EMBL; CH471112; EAW85676.1; -; Genomic_DNA.
DR EMBL; CH471112; EAW85677.1; -; Genomic_DNA.
DR EMBL; CH471112; EAW85678.1; -; Genomic_DNA.
DR EMBL; CH471112; EAW85679.1; -; Genomic_DNA.
DR EMBL; BC000427; AAH00427.1; -; mRNA.
DR EMBL; BC004429; AAH04429.1; -; mRNA.
DR EMBL; BC051289; AAH51289.3; ALT_INIT; mRNA.
DR PIR; JC6056; JC6056.
DR RefSeq; NP_003336.1; NM_003345.4.
DR RefSeq; NP_919235.1; NM_194259.2.
DR RefSeq; NP_919236.1; NM_194260.2.
DR RefSeq; NP_919237.1; NM_194261.2.
DR RefSeq; XP_005255601.1; XM_005255544.1.
DR UniGene; Hs.302903; -.
DR PDB; 1A3S; X-ray; 2.80 A; A=1-158.
DR PDB; 1KPS; X-ray; 2.50 A; A/C=1-158.
DR PDB; 1Z5Q; Model; -; A=1-158.
DR PDB; 1Z5S; X-ray; 3.01 A; A=1-158.
DR PDB; 2GRN; X-ray; 1.80 A; A=1-158.
DR PDB; 2GRO; X-ray; 1.70 A; A=1-158.
DR PDB; 2GRP; X-ray; 2.05 A; A=1-158.
DR PDB; 2GRQ; X-ray; 1.70 A; A=1-158.
DR PDB; 2GRR; X-ray; 1.30 A; A=1-158.
DR PDB; 2O25; X-ray; 2.60 A; C/D=1-158.
DR PDB; 2PE6; X-ray; 2.40 A; A=1-158.
DR PDB; 2PX9; NMR; -; B=1-158.
DR PDB; 2XWU; X-ray; 2.80 A; A=1-158.
DR PDB; 3A4S; X-ray; 2.70 A; A/B=1-158.
DR PDB; 3UIN; X-ray; 2.60 A; A=1-158.
DR PDB; 3UIO; X-ray; 2.60 A; A=1-158.
DR PDB; 3UIP; X-ray; 2.29 A; A=1-158.
DR PDBsum; 1A3S; -.
DR PDBsum; 1KPS; -.
DR PDBsum; 1Z5Q; -.
DR PDBsum; 1Z5S; -.
DR PDBsum; 2GRN; -.
DR PDBsum; 2GRO; -.
DR PDBsum; 2GRP; -.
DR PDBsum; 2GRQ; -.
DR PDBsum; 2GRR; -.
DR PDBsum; 2O25; -.
DR PDBsum; 2PE6; -.
DR PDBsum; 2PX9; -.
DR PDBsum; 2XWU; -.
DR PDBsum; 3A4S; -.
DR PDBsum; 3UIN; -.
DR PDBsum; 3UIO; -.
DR PDBsum; 3UIP; -.
DR ProteinModelPortal; P63279; -.
DR SMR; P63279; 1-157.
DR DIP; DIP-29078N; -.
DR IntAct; P63279; 138.
DR MINT; MINT-137807; -.
DR STRING; 9606.ENSP00000324897; -.
DR BindingDB; P63279; -.
DR TCDB; 3.A.20.1.1; the peroxisomal protein importer (ppi) family.
DR PhosphoSite; P63279; -.
DR DMDM; 54039791; -.
DR PaxDb; P63279; -.
DR PeptideAtlas; P63279; -.
DR PRIDE; P63279; -.
DR DNASU; 7329; -.
DR Ensembl; ENST00000325437; ENSP00000324897; ENSG00000103275.
DR Ensembl; ENST00000355803; ENSP00000348056; ENSG00000103275.
DR Ensembl; ENST00000397514; ENSP00000380649; ENSG00000103275.
DR Ensembl; ENST00000397515; ENSP00000380650; ENSG00000103275.
DR Ensembl; ENST00000403747; ENSP00000385009; ENSG00000103275.
DR Ensembl; ENST00000406620; ENSP00000384568; ENSG00000103275.
DR Ensembl; ENST00000566587; ENSP00000457064; ENSG00000103275.
DR GeneID; 7329; -.
DR KEGG; hsa:7329; -.
DR UCSC; uc002clc.2; human.
DR CTD; 7329; -.
DR GeneCards; GC16P001359; -.
DR HGNC; HGNC:12485; UBE2I.
DR HPA; CAB009021; -.
DR HPA; HPA003909; -.
DR MIM; 601661; gene.
DR neXtProt; NX_P63279; -.
DR PharmGKB; PA37134; -.
DR eggNOG; COG5078; -.
DR HOGENOM; HOG000233454; -.
DR HOVERGEN; HBG063308; -.
DR KO; K10577; -.
DR OMA; WEGGVYK; -.
DR OrthoDB; EOG7B8S5F; -.
DR Reactome; REACT_111183; Meiosis.
DR Reactome; REACT_115566; Cell Cycle.
DR Reactome; REACT_17015; Metabolism of proteins.
DR SignaLink; P63279; -.
DR UniPathway; UPA00886; -.
DR ChiTaRS; UBE2I; human.
DR EvolutionaryTrace; P63279; -.
DR GeneWiki; UBE2I; -.
DR GenomeRNAi; 7329; -.
DR NextBio; 28682; -.
DR PRO; PR:P63279; -.
DR ArrayExpress; P63279; -.
DR Bgee; P63279; -.
DR CleanEx; HS_UBE2I; -.
DR Genevestigator; P63279; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0030425; C:dendrite; IEA:Ensembl.
DR GO; GO:0001650; C:fibrillar center; IEA:Ensembl.
DR GO; GO:0016605; C:PML body; IDA:UniProtKB.
DR GO; GO:0045202; C:synapse; IEA:Ensembl.
DR GO; GO:0000795; C:synaptonemal complex; TAS:ProtInc.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019789; F:SUMO ligase activity; IEA:Ensembl.
DR GO; GO:0004842; F:ubiquitin-protein ligase activity; TAS:BHF-UCL.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0007059; P:chromosome segregation; IEA:UniProtKB-KW.
DR GO; GO:0007067; P:mitosis; IEA:UniProtKB-KW.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IMP:BHF-UCL.
DR GO; GO:0033145; P:positive regulation of intracellular steroid hormone receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0051091; P:positive regulation of sequence-specific DNA binding transcription factor activity; IEA:Ensembl.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IEA:Ensembl.
DR GO; GO:0016925; P:protein sumoylation; IDA:BHF-UCL.
DR GO; GO:0010469; P:regulation of receptor activity; IEA:Ensembl.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; TAS:ProtInc.
DR Gene3D; 3.10.110.10; -; 1.
DR InterPro; IPR027230; Ubc9.
DR InterPro; IPR000608; UBQ-conjugat_E2.
DR InterPro; IPR023313; UBQ-conjugating_AS.
DR InterPro; IPR016135; UBQ-conjugating_enzyme/RWD.
DR PANTHER; PTHR24067:SF51; PTHR24067:SF51; 1.
DR Pfam; PF00179; UQ_con; 1.
DR SUPFAM; SSF54495; SSF54495; 1.
DR PROSITE; PS00183; UBIQUITIN_CONJUGAT_1; 1.
DR PROSITE; PS50127; UBIQUITIN_CONJUGAT_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; ATP-binding; Cell cycle; Cell division;
KW Chromosome partition; Complete proteome; Cytoplasm;
KW Host-virus interaction; Isopeptide bond; Ligase; Mitosis;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Ubl conjugation; Ubl conjugation pathway.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 158 SUMO-conjugating enzyme UBC9.
FT /FTId=PRO_0000082454.
FT REGION 13 18 Interaction with SUMO1.
FT ACT_SITE 93 93 Glycyl thioester intermediate.
FT SITE 4 4 Interaction with RANBP2.
FT SITE 25 25 Interaction with RANBP2.
FT SITE 57 57 Interaction with RANBP2.
FT SITE 100 101 Substrate binding.
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 65 65 N6-acetyllysine.
FT MOD_RES 71 71 Phosphoserine; by CDK1.
FT CROSSLNK 18 18 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ubiquitin).
FT MUTAGEN 13 14 RK->AA: Impairs binding to SUMO1 and
FT catalytic activity.
FT MUTAGEN 17 18 RK->AA: Impairs binding to SUMO1 and
FT catalytic activity.
FT MUTAGEN 22 22 F->A: Impairs binding to RANBP2.
FT MUTAGEN 25 25 V->A: Impairs binding to RANBP2.
FT MUTAGEN 27 27 V->A: Impairs binding to RANBP2.
FT MUTAGEN 42 42 E->A: Slightly impairs binding to RANBP2.
FT MUTAGEN 48 48 K->A: Slightly impairs binding to RANBP2.
FT MUTAGEN 54 54 E->A: Slightly impairs binding to RANBP2.
FT MUTAGEN 57 57 L->A: Impairs binding to RANBP2.
FT MUTAGEN 59 59 K->A: Impairs binding to RANBP2.
FT MUTAGEN 61 61 R->A: Slightly impairs binding to RANBP2.
FT MUTAGEN 85 85 N->Q: Impairs catalytic activity.
FT MUTAGEN 87 87 Y->A: Impairs catalytic activity.
FT MUTAGEN 93 93 C->S: Loss of enhancement of sumoylation
FT by RWDD3. No effect on RWDD3 protein
FT levels.
FT MUTAGEN 100 101 DK->AA: Impairs catalytic activity.
FT MUTAGEN 127 127 D->A: Impairs catalytic activity.
FT MUTAGEN 127 127 D->S: No effect on catalytic activity.
FT CONFLICT 18 18 K -> P (in Ref. 6; AAC50603).
FT CONFLICT 86 89 VYPS -> GVPF (in Ref. 6; AAC50603).
FT HELIX 3 18
FT STRAND 25 30
FT STRAND 32 34
FT STRAND 36 46
FT TURN 52 55
FT STRAND 57 63
FT TURN 66 69
FT STRAND 74 79
FT STRAND 90 92
FT HELIX 95 97
FT TURN 99 102
FT HELIX 109 121
FT HELIX 131 139
FT HELIX 141 154
SQ SEQUENCE 158 AA; 18007 MW; E2C826E9C8D0683D CRC64;
MSGIALSRLA QERKAWRKDH PFGFVAVPTK NPDGTMNLMN WECAIPGKKG TPWEGGLFKL
RMLFKDDYPS SPPKCKFEPP LFHPNVYPSG TVCLSILEED KDWRPAITIK QILLGIQELL
NEPNIQDPAQ AEAYTIYCQN RVEYEKRVRA QAKKFAPS
//
MIM
601661
*RECORD*
*FIELD* NO
601661
*FIELD* TI
*601661 UBIQUITIN-CONJUGATING ENZYME E2I; UBE2I
;;UBIQUITIN-CONJUGATING ENZYME UBC9, YEAST, HOMOLOG OF; UBC9
read more*FIELD* TX
CLONING
The ubiquitin-conjugating enzymes (E2s) are a family of proteins
involved in the ubiquitin-dependent protein degradation system. In
yeast, at least 10 different E2s have been identified; they are involved
in essential cellular processes such as DNA repair, cell cycle control,
and stress responses. Using the yeast 2-hybrid system with the repressor
domain of the Wilms tumor gene product (WT1; 607102) as bait, Wang et
al. (1996) isolated a cDNA encoding a human homolog of the yeast
ubiquitin-conjugating enzyme-9 (UBC9). Human UBC9 has 56% identity with
yeast ubc9 and contains the active site cysteine necessary for the
ubiquitin-conjugating activity of all E2 enzymes. Northern blot analysis
revealed human UBC9 transcripts of 4.4, 2.4, and 1.3 kb in all of the
tissues examined.
Watanabe et al. (1996) likewise cloned UBE2I, a human homolog of yeast
ubc9. The deduced protein contains 158 amino acids.
Yasugi and Howley (1996) independently isolated the human UBC9 gene.
Nacerddine et al. (2005) stated that the human and mouse UBC9 proteins
are 100% identical. Rajan et al. (2005) stated that the human and
Xenopus UBC9 proteins are identical.
GENE FUNCTION
Wang et al. (1996) found that human UBC9 could fully complement the
mutant phenotype of a yeast ubc9 mutant strain. In yeast, ubc9 is
involved in cell cycle progression via degradation of cyclins (see
123835). Wang et al. (1996) suggested that human UBC9 may play a similar
role via interaction with WT1, which is able to impose a block to cell
cycle progression in eukaryotic cells.
Yasugi and Howley (1996) found that human UBC9 could support the growth
of yeast ubc9 temperature-sensitive mutants at nonpermissive
temperatures, indicating that the gene is a functional homolog of yeast
ubc9.
A sumoylated form of RANGAP1 (602362) associates with the nuclear pore
complex and is required for import of proteins into the nucleus. Okuma
et al. (1999) showed that SUA1 (SAE1; 613294), UBA2 (613295), and UBC9
catalyzed in vitro sumoylation of RANGAP1. Faint RANGAP1 modification
was observed in the absence of UBC9. Okuma et al. (1999) concluded that,
in contrast to the 3-step ubiquitination reaction, which requires an E1
ubiquitin-activating enzyme, an E2 ubiquitin-conjugating enzyme, and an
E3 ubiquitin ligase, sumoylation is a 2-step reaction in which the
SUA1/UBA2 dimer functions as an E1 enzyme and UBC9 functions as an E2
enzyme.
Fragile histidine triad (FHIT; 601153), a candidate tumor suppressor
gene located on 3p14.2, is deleted in many types of human cancer. Using
a yeast 2-hybrid screen to search for proteins that interact with the
FHIT protein in vivo, Shi et al. (2000) found that UBC9 is specifically
associated with FHIT. The last 21 amino acids at the C terminus of UBC9
appear to be unimportant for its biologic activity, since a UBC9 mutant
harboring a deletion of these amino acids could still restore normal
growth of yeast containing a temperature-sensitive mutation in the
homolog UBC9 gene. Mutational analysis indicated that UBC9 was
associated with the C-terminal portion of FHIT. The interaction between
FHIT and UBC9 appeared to be independent of the enzymatic activity of
FHIT. Given that yeast UBC9 is involved in the degradation of S- and
M-phase cyclins, Shi et al. (2000) concluded that FHIT may be involved
in cell cycle control through its interaction with UBC9.
The RAD6 (179095) pathway is central to postreplicative DNA repair in
eukaryotic cells. Two principal elements of this pathway are the
ubiquitin-conjugating enzymes RAD6 and the MMS2 (603001)-UBC13 (603679)
heterodimer, which are recruited to chromatin by the RING finger
proteins RAD18 (605256) and RAD5 (608048), respectively. Hoege et al.
(2002) showed that UBC9, a small ubiquitin-related modifier
(SUMO)-conjugating enzyme, is also affiliated with this pathway and that
proliferating cell nuclear antigen (PCNA; 176740), a DNA polymerase
sliding clamp involved in DNA synthesis and repair, is a substrate. PCNA
is monoubiquitinated through RAD6 and RAD18, modified by lys63-linked
multiubiquitination, which additionally requires MMS2, UBC13, and RAD5,
and is conjugated to SUMO by UBC9. All 3 modifications affect the same
lysine residue of PCNA, K164, suggesting that they label PCNA for
alternative functions. Hoege et al. (2002) demonstrated that these
modifications differentially affect resistance to DNA damage, and that
damage-induced PCNA ubiquitination is elementary for DNA repair and
occurs at the same conserved residue in yeast and humans.
Rajan et al. (2005) found that the potassium channel K2P1 (KCNK1;
601745) was sumoylated on intracellular lys274 by Xenopus or human UBC9
at the cell surface, and that sumoylation rendered the channel inactive.
Mutation of lys274 or desumoylation of K2P1 by SENP1 (612157) activated
the pore, which functioned as a potassium leak channel.
Using immunoblot and proteomic analyses, Ribet et al. (2010) observed a
decrease in both SUMO1 (601912)- and SUMO2 (603042)/SUMO3
(602231)-conjugated proteins of high molecular mass in HeLa cells
infected with Listeria monocytogenes (Lm). The decrease was not observed
in cells infected with nonpathogenic L. inocula or with Lm defective for
listeriolysin (LLO) toxin, and LLO alone triggered a massive decrease in
sumoylated proteins in HeLa and Jeg3 cells. Treatment with LLO alone or
infection with wildtype Lm led to a dramatic decrease in the level of
UBC9, but not of SAE1 or SAE2 (UBA2). The decrease in UBC9 resulted from
degradation of the enzyme rather than altered translation and required
LLO binding to cellular membranes and pore formation. Perfringolysin O
and pneumolysin, LLO-like pore-forming toxins encoded by other bacterial
pathogens, also triggered degradation of UBC9. Overexpression of SUMO1
or SUMO2 in HeLa cells impaired Lm infection. Ribet et al. (2010)
concluded that Listeria, and probably other pathogens, dampen the host
response by decreasing the sumoylation level of proteins critical for
infection by targeting UBC9, an essential enzyme of the SUMO pathway.
BIOCHEMICAL FEATURES
- Crystal Structure
Bernier-Villamor et al. (2002) performed crystallographic analysis of a
complex between mammalian UBC9 and a C-terminal domain of RANGAP1
(602362) at 2.5 angstroms. These experiments revealed structural
determinants for recognition of consensus SUMO (SUMO1; 601912)
modification sequences found within SUMO-conjugated proteins.
Structure-based mutagenesis and biochemical analysis of UBC9 and RANGAP1
revealed distinct motifs required for substrate binding and SUMO
modification of p53 (191170), NFKBIA (164008), and RANGAP1.
Reverter and Lima (2005) described the 3.0-angstrom crystal structure of
a 4-protein complex of UBC9, a NUP358/RANBP2 (601181) E3 ligase domain
(IR1-M), and SUMO1 conjugated to the carboxy-terminal domain of RANGAP1.
Structural insights, combined with biochemical and kinetic data obtained
with additional substrates, supported a model in which NUP358/RANBP2
acts as an E3 by binding both SUMO and UBC9 to position the
SUMO-E2-thioester in an optimal orientation to enhance conjugation.
GENE STRUCTURE
Nacerddine et al. (2005) determined that the mouse Ubc9 gene contains 7
exons.
MAPPING
By fluorescence in situ hybridization (FISH), Wang et al. (1996) mapped
the human UBC9 gene to chromosome 16p13.3. Watanabe et al. (1996) mapped
UBE2I to 16p13.3 by FISH. Tachibana et al. (1996) also mapped UBE2I to
16p13.3 by FISH.
ANIMAL MODEL
To investigate the significance of the SUMO system in mammals,
Nacerddine et al. (2005) generated mice deficient for the Ubc9 protein.
They found that expression of a single Ubc9 allele was sufficient to
generate a normal pattern of Sumo1-conjugated proteins; however,
homozygous Ubc9 deficiency resulted in embryonic lethality. Ubc9-null
embryos died early in development, subsequent to the blastocyst stage
and prior to embryonic day 7.5. In culture, mutant blastocysts were
viable for up to 2 days, but thereafter showed apoptosis of the inner
cell mass. Mutant cells developed chromosome defects and gross
alterations in nuclear organization such as disassembled nucleoli, PML
(102578)-positive nuclear bodies, and misshapen nuclei, as well as
mislocalized Ran (601179) and RanGAP1 (602362). Nacerddine et al. (2005)
concluded that UBC9, and by implication, the SUMO pathway, are crucial
for proper nuclear architecture, accurate chromosome segregation, and
embryonic viability.
*FIELD* RF
1. Bernier-Villamor, V.; Sampson, D. A.; Matunis, M. J.; Lima, C.
D.: Structural basis for E2-mediated SUMO conjugation revealed by
a complex between ubiquitin-conjugating enzyme Ubc9 and RanGAP1. Cell 108:
345-356, 2002.
2. Hoege, C.; Pfander, B.; Moldovan, G.-L.; Pyrowolakis, G.; Jentsch,
S.: RAD6-dependent DNA repair is linked to modification of PCNA by
ubiquitin and SUMO. Nature 419: 135-141, 2002.
3. Nacerddine, K.; Lehembre, F.; Bhaumik, M.; Artus, J.; Cohen-Tannoudji,
M.; Babinet, C.; Pandolfi, P. P.; Dejean, A.: The SUMO pathway is
essential for nuclear integrity and chromosome segregation in mice. Dev.
Cell 9: 769-779, 2005.
4. Okuma, T.; Honda, R.; Ichikawa, G.; Tsumagari, N.; Yasuda, H.:
In vitro SUMO-1 modification requires two enzymatic steps, E1 and
E2. Biochem. Biophys. Res. Commun. 254: 693-698, 1999.
5. Rajan, S.; Plant, L. D.; Rabin, M. L.; Butler, M. H.; Goldstein,
S. A. N.: Sumoylation silences the plasma membrane leak K(+) channel
K2P1. Cell 121: 37-47, 2005. Note: Erratum: Cell 141: 368 only,
2010.
6. Reverter, D.; Lima, C. D.: Insights into E3 ligase activity revealed
by a SUMO-RanGAP1-Ubc9-Nup358 complex. (Letter) Nature 435: 687-692,
2005.
7. Ribet, D.; Hamon, M.; Gouin, E.; Nahori, M.-A.; Impens, F.; Neyret-Kahn,
H.; Gevaert, K.; Vandekerckhove, J.; Dejean, A.; Cossart, P.: Listeria
monocytogenes impairs SUMOylation for efficient infection. Nature 464:
1192-1195, 2010.
8. Shi, Y.; Zou, M.; Farid, N. R.; Paterson, M. C.: Association of
FHIT (fragile histidine triad), a candidate tumour suppressor gene,
with the ubiquitin-conjugating enzyme hUBC9. Biochem. J. 352: 443-448,
2000.
9. Tachibana, M.; Iwata, N.; Watanabe, A.; Nobukuni, Y.; Ploplis,
B.; Kajigaya, S.: Assignment of the gene for a ubiquitin-conjugating
enzyme (UBE2I) to human chromosome band 16p13.3 by in situ hybridization. Cytogenet.
Cell Genet. 75: 222-223, 1996.
10. Wang, Z.-Y.; Qiu, Q.-Q.; Seufert, W.; Taguchi, T.; Testa, J. R.;
Whitmore, S. A.; Callen, D. F.; Welsh, D.; Shenk, T.; Deuel, T. F.
: Molecular cloning of the cDNA and chromosome localization of the
gene for human ubiquitin-conjugating enzyme 9. J. Biol. Chem. 271:
24811-24816, 1996.
11. Watanabe, T. K.; Fujiwara, T.; Kawai, A.; Shimizu, F.; Takami,
S.; Hirano, H.; Okuno, S.; Ozaki, K.; Takeda, S.; Shimada, Y.; Nagata,
M.; Takaichi, A.; Takahashi, E.; Nakamura, Y.; Shin, S.: Cloning,
expression, and mapping of UBE2I, a novel gene encoding a human homologue
of yeast ubiquitin-conjugating enzymes which are critical for regulating
the cell cycle. Cytogenet. Cell Genet. 72: 86-89, 1996.
12. Yasugi, T.; Howley, P. M.: Identification of the structural and
functional human homolog of the yeast ubiquitin conjugating enzyme
UBC9. Nucleic Acids Res. 24: 2005-2010, 1996.
*FIELD* CN
Patricia A. Hartz - updated: 9/21/2010
Paul J. Converse - updated: 5/12/2010
Patricia A. Hartz - updated: 3/4/2010
Patricia A. Hartz - updated: 1/17/2006
Ada Hamosh - updated: 6/15/2005
Ada Hamosh - updated: 9/30/2002
Victor A. McKusick - updated: 8/23/2002
Stylianos E. Antonarakis - updated: 3/22/2002
Lori M. Kelman - updated: 5/12/1997
Victor A. McKusick - updated: 4/25/1997
Mark H. Paalman - updated: 2/12/1997
*FIELD* CD
Jennifer P. Macke: 2/4/1997
*FIELD* ED
terry: 09/17/2012
mgross: 9/21/2010
mgross: 5/12/2010
mgross: 3/4/2010
terry: 3/4/2010
carol: 2/3/2009
alopez: 1/29/2007
alopez: 2/16/2006
terry: 1/17/2006
alopez: 6/16/2005
terry: 6/15/2005
alopez: 10/1/2002
tkritzer: 9/30/2002
ckniffin: 9/11/2002
tkritzer: 9/9/2002
tkritzer: 8/28/2002
terry: 8/23/2002
mgross: 3/22/2002
carol: 7/8/1998
alopez: 6/4/1997
alopez: 5/30/1997
alopez: 5/12/1997
terry: 4/25/1997
mark: 2/25/1997
mark: 2/12/1997
terry: 2/12/1997
jamie: 2/4/1997
*RECORD*
*FIELD* NO
601661
*FIELD* TI
*601661 UBIQUITIN-CONJUGATING ENZYME E2I; UBE2I
;;UBIQUITIN-CONJUGATING ENZYME UBC9, YEAST, HOMOLOG OF; UBC9
read more*FIELD* TX
CLONING
The ubiquitin-conjugating enzymes (E2s) are a family of proteins
involved in the ubiquitin-dependent protein degradation system. In
yeast, at least 10 different E2s have been identified; they are involved
in essential cellular processes such as DNA repair, cell cycle control,
and stress responses. Using the yeast 2-hybrid system with the repressor
domain of the Wilms tumor gene product (WT1; 607102) as bait, Wang et
al. (1996) isolated a cDNA encoding a human homolog of the yeast
ubiquitin-conjugating enzyme-9 (UBC9). Human UBC9 has 56% identity with
yeast ubc9 and contains the active site cysteine necessary for the
ubiquitin-conjugating activity of all E2 enzymes. Northern blot analysis
revealed human UBC9 transcripts of 4.4, 2.4, and 1.3 kb in all of the
tissues examined.
Watanabe et al. (1996) likewise cloned UBE2I, a human homolog of yeast
ubc9. The deduced protein contains 158 amino acids.
Yasugi and Howley (1996) independently isolated the human UBC9 gene.
Nacerddine et al. (2005) stated that the human and mouse UBC9 proteins
are 100% identical. Rajan et al. (2005) stated that the human and
Xenopus UBC9 proteins are identical.
GENE FUNCTION
Wang et al. (1996) found that human UBC9 could fully complement the
mutant phenotype of a yeast ubc9 mutant strain. In yeast, ubc9 is
involved in cell cycle progression via degradation of cyclins (see
123835). Wang et al. (1996) suggested that human UBC9 may play a similar
role via interaction with WT1, which is able to impose a block to cell
cycle progression in eukaryotic cells.
Yasugi and Howley (1996) found that human UBC9 could support the growth
of yeast ubc9 temperature-sensitive mutants at nonpermissive
temperatures, indicating that the gene is a functional homolog of yeast
ubc9.
A sumoylated form of RANGAP1 (602362) associates with the nuclear pore
complex and is required for import of proteins into the nucleus. Okuma
et al. (1999) showed that SUA1 (SAE1; 613294), UBA2 (613295), and UBC9
catalyzed in vitro sumoylation of RANGAP1. Faint RANGAP1 modification
was observed in the absence of UBC9. Okuma et al. (1999) concluded that,
in contrast to the 3-step ubiquitination reaction, which requires an E1
ubiquitin-activating enzyme, an E2 ubiquitin-conjugating enzyme, and an
E3 ubiquitin ligase, sumoylation is a 2-step reaction in which the
SUA1/UBA2 dimer functions as an E1 enzyme and UBC9 functions as an E2
enzyme.
Fragile histidine triad (FHIT; 601153), a candidate tumor suppressor
gene located on 3p14.2, is deleted in many types of human cancer. Using
a yeast 2-hybrid screen to search for proteins that interact with the
FHIT protein in vivo, Shi et al. (2000) found that UBC9 is specifically
associated with FHIT. The last 21 amino acids at the C terminus of UBC9
appear to be unimportant for its biologic activity, since a UBC9 mutant
harboring a deletion of these amino acids could still restore normal
growth of yeast containing a temperature-sensitive mutation in the
homolog UBC9 gene. Mutational analysis indicated that UBC9 was
associated with the C-terminal portion of FHIT. The interaction between
FHIT and UBC9 appeared to be independent of the enzymatic activity of
FHIT. Given that yeast UBC9 is involved in the degradation of S- and
M-phase cyclins, Shi et al. (2000) concluded that FHIT may be involved
in cell cycle control through its interaction with UBC9.
The RAD6 (179095) pathway is central to postreplicative DNA repair in
eukaryotic cells. Two principal elements of this pathway are the
ubiquitin-conjugating enzymes RAD6 and the MMS2 (603001)-UBC13 (603679)
heterodimer, which are recruited to chromatin by the RING finger
proteins RAD18 (605256) and RAD5 (608048), respectively. Hoege et al.
(2002) showed that UBC9, a small ubiquitin-related modifier
(SUMO)-conjugating enzyme, is also affiliated with this pathway and that
proliferating cell nuclear antigen (PCNA; 176740), a DNA polymerase
sliding clamp involved in DNA synthesis and repair, is a substrate. PCNA
is monoubiquitinated through RAD6 and RAD18, modified by lys63-linked
multiubiquitination, which additionally requires MMS2, UBC13, and RAD5,
and is conjugated to SUMO by UBC9. All 3 modifications affect the same
lysine residue of PCNA, K164, suggesting that they label PCNA for
alternative functions. Hoege et al. (2002) demonstrated that these
modifications differentially affect resistance to DNA damage, and that
damage-induced PCNA ubiquitination is elementary for DNA repair and
occurs at the same conserved residue in yeast and humans.
Rajan et al. (2005) found that the potassium channel K2P1 (KCNK1;
601745) was sumoylated on intracellular lys274 by Xenopus or human UBC9
at the cell surface, and that sumoylation rendered the channel inactive.
Mutation of lys274 or desumoylation of K2P1 by SENP1 (612157) activated
the pore, which functioned as a potassium leak channel.
Using immunoblot and proteomic analyses, Ribet et al. (2010) observed a
decrease in both SUMO1 (601912)- and SUMO2 (603042)/SUMO3
(602231)-conjugated proteins of high molecular mass in HeLa cells
infected with Listeria monocytogenes (Lm). The decrease was not observed
in cells infected with nonpathogenic L. inocula or with Lm defective for
listeriolysin (LLO) toxin, and LLO alone triggered a massive decrease in
sumoylated proteins in HeLa and Jeg3 cells. Treatment with LLO alone or
infection with wildtype Lm led to a dramatic decrease in the level of
UBC9, but not of SAE1 or SAE2 (UBA2). The decrease in UBC9 resulted from
degradation of the enzyme rather than altered translation and required
LLO binding to cellular membranes and pore formation. Perfringolysin O
and pneumolysin, LLO-like pore-forming toxins encoded by other bacterial
pathogens, also triggered degradation of UBC9. Overexpression of SUMO1
or SUMO2 in HeLa cells impaired Lm infection. Ribet et al. (2010)
concluded that Listeria, and probably other pathogens, dampen the host
response by decreasing the sumoylation level of proteins critical for
infection by targeting UBC9, an essential enzyme of the SUMO pathway.
BIOCHEMICAL FEATURES
- Crystal Structure
Bernier-Villamor et al. (2002) performed crystallographic analysis of a
complex between mammalian UBC9 and a C-terminal domain of RANGAP1
(602362) at 2.5 angstroms. These experiments revealed structural
determinants for recognition of consensus SUMO (SUMO1; 601912)
modification sequences found within SUMO-conjugated proteins.
Structure-based mutagenesis and biochemical analysis of UBC9 and RANGAP1
revealed distinct motifs required for substrate binding and SUMO
modification of p53 (191170), NFKBIA (164008), and RANGAP1.
Reverter and Lima (2005) described the 3.0-angstrom crystal structure of
a 4-protein complex of UBC9, a NUP358/RANBP2 (601181) E3 ligase domain
(IR1-M), and SUMO1 conjugated to the carboxy-terminal domain of RANGAP1.
Structural insights, combined with biochemical and kinetic data obtained
with additional substrates, supported a model in which NUP358/RANBP2
acts as an E3 by binding both SUMO and UBC9 to position the
SUMO-E2-thioester in an optimal orientation to enhance conjugation.
GENE STRUCTURE
Nacerddine et al. (2005) determined that the mouse Ubc9 gene contains 7
exons.
MAPPING
By fluorescence in situ hybridization (FISH), Wang et al. (1996) mapped
the human UBC9 gene to chromosome 16p13.3. Watanabe et al. (1996) mapped
UBE2I to 16p13.3 by FISH. Tachibana et al. (1996) also mapped UBE2I to
16p13.3 by FISH.
ANIMAL MODEL
To investigate the significance of the SUMO system in mammals,
Nacerddine et al. (2005) generated mice deficient for the Ubc9 protein.
They found that expression of a single Ubc9 allele was sufficient to
generate a normal pattern of Sumo1-conjugated proteins; however,
homozygous Ubc9 deficiency resulted in embryonic lethality. Ubc9-null
embryos died early in development, subsequent to the blastocyst stage
and prior to embryonic day 7.5. In culture, mutant blastocysts were
viable for up to 2 days, but thereafter showed apoptosis of the inner
cell mass. Mutant cells developed chromosome defects and gross
alterations in nuclear organization such as disassembled nucleoli, PML
(102578)-positive nuclear bodies, and misshapen nuclei, as well as
mislocalized Ran (601179) and RanGAP1 (602362). Nacerddine et al. (2005)
concluded that UBC9, and by implication, the SUMO pathway, are crucial
for proper nuclear architecture, accurate chromosome segregation, and
embryonic viability.
*FIELD* RF
1. Bernier-Villamor, V.; Sampson, D. A.; Matunis, M. J.; Lima, C.
D.: Structural basis for E2-mediated SUMO conjugation revealed by
a complex between ubiquitin-conjugating enzyme Ubc9 and RanGAP1. Cell 108:
345-356, 2002.
2. Hoege, C.; Pfander, B.; Moldovan, G.-L.; Pyrowolakis, G.; Jentsch,
S.: RAD6-dependent DNA repair is linked to modification of PCNA by
ubiquitin and SUMO. Nature 419: 135-141, 2002.
3. Nacerddine, K.; Lehembre, F.; Bhaumik, M.; Artus, J.; Cohen-Tannoudji,
M.; Babinet, C.; Pandolfi, P. P.; Dejean, A.: The SUMO pathway is
essential for nuclear integrity and chromosome segregation in mice. Dev.
Cell 9: 769-779, 2005.
4. Okuma, T.; Honda, R.; Ichikawa, G.; Tsumagari, N.; Yasuda, H.:
In vitro SUMO-1 modification requires two enzymatic steps, E1 and
E2. Biochem. Biophys. Res. Commun. 254: 693-698, 1999.
5. Rajan, S.; Plant, L. D.; Rabin, M. L.; Butler, M. H.; Goldstein,
S. A. N.: Sumoylation silences the plasma membrane leak K(+) channel
K2P1. Cell 121: 37-47, 2005. Note: Erratum: Cell 141: 368 only,
2010.
6. Reverter, D.; Lima, C. D.: Insights into E3 ligase activity revealed
by a SUMO-RanGAP1-Ubc9-Nup358 complex. (Letter) Nature 435: 687-692,
2005.
7. Ribet, D.; Hamon, M.; Gouin, E.; Nahori, M.-A.; Impens, F.; Neyret-Kahn,
H.; Gevaert, K.; Vandekerckhove, J.; Dejean, A.; Cossart, P.: Listeria
monocytogenes impairs SUMOylation for efficient infection. Nature 464:
1192-1195, 2010.
8. Shi, Y.; Zou, M.; Farid, N. R.; Paterson, M. C.: Association of
FHIT (fragile histidine triad), a candidate tumour suppressor gene,
with the ubiquitin-conjugating enzyme hUBC9. Biochem. J. 352: 443-448,
2000.
9. Tachibana, M.; Iwata, N.; Watanabe, A.; Nobukuni, Y.; Ploplis,
B.; Kajigaya, S.: Assignment of the gene for a ubiquitin-conjugating
enzyme (UBE2I) to human chromosome band 16p13.3 by in situ hybridization. Cytogenet.
Cell Genet. 75: 222-223, 1996.
10. Wang, Z.-Y.; Qiu, Q.-Q.; Seufert, W.; Taguchi, T.; Testa, J. R.;
Whitmore, S. A.; Callen, D. F.; Welsh, D.; Shenk, T.; Deuel, T. F.
: Molecular cloning of the cDNA and chromosome localization of the
gene for human ubiquitin-conjugating enzyme 9. J. Biol. Chem. 271:
24811-24816, 1996.
11. Watanabe, T. K.; Fujiwara, T.; Kawai, A.; Shimizu, F.; Takami,
S.; Hirano, H.; Okuno, S.; Ozaki, K.; Takeda, S.; Shimada, Y.; Nagata,
M.; Takaichi, A.; Takahashi, E.; Nakamura, Y.; Shin, S.: Cloning,
expression, and mapping of UBE2I, a novel gene encoding a human homologue
of yeast ubiquitin-conjugating enzymes which are critical for regulating
the cell cycle. Cytogenet. Cell Genet. 72: 86-89, 1996.
12. Yasugi, T.; Howley, P. M.: Identification of the structural and
functional human homolog of the yeast ubiquitin conjugating enzyme
UBC9. Nucleic Acids Res. 24: 2005-2010, 1996.
*FIELD* CN
Patricia A. Hartz - updated: 9/21/2010
Paul J. Converse - updated: 5/12/2010
Patricia A. Hartz - updated: 3/4/2010
Patricia A. Hartz - updated: 1/17/2006
Ada Hamosh - updated: 6/15/2005
Ada Hamosh - updated: 9/30/2002
Victor A. McKusick - updated: 8/23/2002
Stylianos E. Antonarakis - updated: 3/22/2002
Lori M. Kelman - updated: 5/12/1997
Victor A. McKusick - updated: 4/25/1997
Mark H. Paalman - updated: 2/12/1997
*FIELD* CD
Jennifer P. Macke: 2/4/1997
*FIELD* ED
terry: 09/17/2012
mgross: 9/21/2010
mgross: 5/12/2010
mgross: 3/4/2010
terry: 3/4/2010
carol: 2/3/2009
alopez: 1/29/2007
alopez: 2/16/2006
terry: 1/17/2006
alopez: 6/16/2005
terry: 6/15/2005
alopez: 10/1/2002
tkritzer: 9/30/2002
ckniffin: 9/11/2002
tkritzer: 9/9/2002
tkritzer: 8/28/2002
terry: 8/23/2002
mgross: 3/22/2002
carol: 7/8/1998
alopez: 6/4/1997
alopez: 5/30/1997
alopez: 5/12/1997
terry: 4/25/1997
mark: 2/25/1997
mark: 2/12/1997
terry: 2/12/1997
jamie: 2/4/1997