SUMO2_HUMAN
ID SUMO2_HUMAN Reviewed; 95 AA.
AC P61956; B2R4I2; P55855; Q32Q42; Q6IPZ6; Q96HK1;
DT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT 22-FEB-2012, sequence version 3.
DT 03-AUG-2022, entry version 192.
DE RecName: Full=Small ubiquitin-related modifier 2 {ECO:0000305};
DE Short=SUMO-2 {ECO:0000305};
DE AltName: Full=HSMT3 {ECO:0000303|PubMed:8630065};
DE AltName: Full=SMT3 homolog 2 {ECO:0000312|HGNC:HGNC:11125};
DE AltName: Full=SUMO-3 {ECO:0000303|PubMed:10692421};
DE AltName: Full=Sentrin-2 {ECO:0000303|PubMed:9556629};
DE AltName: Full=Ubiquitin-like protein SMT3B {ECO:0000305};
DE Short=Smt3B {ECO:0000303|PubMed:10692421};
DE Flags: Precursor;
GN Name=SUMO2 {ECO:0000312|HGNC:HGNC:11125};
GN Synonyms=SMT3B {ECO:0000303|PubMed:10692421, ECO:0000312|HGNC:HGNC:11125},
GN SMT3H2;
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] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=8630065; DOI=10.1006/bbrc.1996.0717;
RA Mannen H., Tseng H.M., Cho C.L., Li S.S.-L.;
RT "Cloning and expression of human homolog HSMT3 to yeast SMT3 suppressor of
RT MIF2 mutations in a centromere protein gene.";
RL Biochem. Biophys. Res. Commun. 222:178-180(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=9119407; DOI=10.1006/geno.1996.4556;
RA Lapenta V., Chiurazzi P., van der Spek P.J., Pizzuti A., Hanaoka F.,
RA Brahe C.;
RT "SMT3A, a human homologue of the S. cerevisiae SMT3 gene, maps to
RT chromosome 21qter and defines a novel gene family.";
RL Genomics 40:362-367(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Cerebellum;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP ASN-16.
RC TISSUE=Blood vessel, Bone, Bone marrow, Brain, Lung, Skin, and Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP FUNCTION, PROTEOLYTIC CLEAVAGE, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=9556629; DOI=10.1074/jbc.273.18.11349;
RA Kamitani T., Kito K., Nguyen H.P., Fukuda-Kamitani T., Yeh E.T.H.;
RT "Characterization of a second member of the sentrin family of ubiquitin-
RT like proteins.";
RL J. Biol. Chem. 273:11349-11353(1998).
RN [8]
RP IDENTIFICATION, AND NOMENCLATURE.
RX PubMed=10692421; DOI=10.1074/jbc.275.9.6252;
RA Saitoh H., Hinchey J.;
RT "Functional heterogeneity of small ubiquitin-related protein modifiers
RT SUMO-1 versus SUMO-2/3.";
RL J. Biol. Chem. 275:6252-6258(2000).
RN [9]
RP SUMOYLATION AT LYS-11, AND MUTAGENESIS OF LYS-11.
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 substrates
RT by SAE1/SAE2 and Ubc9.";
RL J. Biol. Chem. 276:35368-35374(2001).
RN [10]
RP SUBCELLULAR LOCATION.
RX PubMed=12383504; DOI=10.1016/s0378-1119(02)00843-0;
RA Su H.-L., Li S.S.-L.;
RT "Molecular features of human ubiquitin-like SUMO genes and their encoded
RT proteins.";
RL Gene 296:65-73(2002).
RN [11]
RP INTERACTION WITH UBE2I.
RX PubMed=12924945; DOI=10.1021/bi0345283;
RA Tatham M.H., Kim S., Yu B., Jaffray E., Song J., Zheng J., Rodriguez M.S.,
RA 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 [12]
RP CLEAVAGE.
RX PubMed=15296745; DOI=10.1016/j.str.2004.05.023;
RA Reverter D., Lima C.D.;
RT "A basis for SUMO protease specificity provided by analysis of human Senp2
RT and a Senp2-SUMO complex.";
RL Structure 12:1519-1531(2004).
RN [13]
RP CLEAVAGE.
RX PubMed=15487983; DOI=10.1042/bj20041210;
RA Xu Z., Au S.W.N.;
RT "Mapping residues of SUMO precursors essential in differential maturation
RT by SUMO-specific protease, SENP1.";
RL Biochem. J. 386:325-330(2005).
RN [14]
RP INTERACTION WITH PELP1.
RX PubMed=16567619; DOI=10.1073/pnas.0601066103;
RA Rosendorff A., Sakakibara S., Lu S., Kieff E., Xuan Y., DiBacco A., Shi Y.,
RA Shi Y., Gill G.;
RT "NXP-2 association with SUMO-2 depends on lysines required for
RT transcriptional repression.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:5308-5313(2006).
RN [15]
RP FUNCTION IN SUMOYLATION OF USP25, AND INTERACTION WITH USP25.
RX PubMed=18538659; DOI=10.1016/j.molcel.2008.03.021;
RA Meulmeester E., Kunze M., Hsiao H.H., Urlaub H., Melchior F.;
RT "Mechanism and consequences for paralog-specific sumoylation of ubiquitin-
RT specific protease 25.";
RL Mol. Cell 30:610-619(2008).
RN [16]
RP FUNCTION, AND POLYUBIQUITINATION AT LYS-11 BY RNF4.
RX PubMed=18408734; DOI=10.1038/ncb1716;
RA Tatham M.H., Geoffroy M.C., Shen L., Plechanovova A., Hattersley N.,
RA Jaffray E.G., Palvimo J.J., Hay R.T.;
RT "RNF4 is a poly-SUMO-specific E3 ubiquitin ligase required for arsenic-
RT induced PML degradation.";
RL Nat. Cell Biol. 10:538-546(2008).
RN [17]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-11, 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 [18]
RP SUMOYLATION AT LYS-11.
RC TISSUE=Cervix carcinoma;
RX PubMed=20388717; DOI=10.1074/jbc.m110.106955;
RA Blomster H.A., Imanishi S.Y., Siimes J., Kastu J., Morrice N.A.,
RA Eriksson J.E., Sistonen L.;
RT "In vivo identification of sumoylation sites by a signature tag and
RT cysteine-targeted affinity purification.";
RL J. Biol. Chem. 285:19324-19329(2010).
RN [19]
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 [20]
RP FUNCTION, INTERACTION WITH MTA1, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP LYS-33; LYS-35 AND LYS-42.
RX PubMed=21965678; DOI=10.1074/jbc.m111.267237;
RA Cong L., Pakala S.B., Ohshiro K., Li D.Q., Kumar R.;
RT "SUMOylation and SUMO-interacting motif (SIM) of metastasis tumor antigen 1
RT (MTA1) synergistically regulate its transcriptional repressor function.";
RL J. Biol. Chem. 286:43793-43808(2011).
RN [21]
RP SUBCELLULAR LOCATION.
RX PubMed=22406621; DOI=10.1158/0008-5472.can-11-3159;
RA Rabellino A., Carter B., Konstantinidou G., Wu S.Y., Rimessi A.,
RA Byers L.A., Heymach J.V., Girard L., Chiang C.M., Teruya-Feldstein J.,
RA Scaglioni P.P.;
RT "The SUMO E3-ligase PIAS1 regulates the tumor suppressor PML and its
RT oncogenic counterpart PML-RARA.";
RL Cancer Res. 72:2275-2284(2012).
RN [22]
RP IDENTIFICATION OF REPEAT SUMO-INTERACTING MOTIF, AND INTERACTION WITH
RP SIMC1; CASP8AP2; RNF111 AND SOBP.
RX PubMed=23086935; DOI=10.1074/jbc.m112.410985;
RA Sun H., Hunter T.;
RT "PolySUMO-binding proteins identified through a string search.";
RL J. Biol. Chem. 287:42071-42083(2012).
RN [23]
RP INTERACTION WITH EPSTEIN-BARR VIRUS BGLF4.
RX PubMed=22398289; DOI=10.1128/jvi.00314-12;
RA Li R., Wang L., Liao G., Guzzo C.M., Matunis M.J., Zhu H., Hayward S.D.;
RT "SUMO binding by the Epstein-Barr virus protein kinase BGLF4 is crucial for
RT BGLF4 function.";
RL J. Virol. 86:5412-5421(2012).
RN [24]
RP UBIQUITINATION AT MET-1.
RX PubMed=23560854; DOI=10.1042/bj20130244;
RA Tatham M.H., Plechanovova A., Jaffray E.G., Salmen H., Hay R.T.;
RT "Ube2W conjugates ubiquitin to alpha-amino groups of protein N-termini.";
RL Biochem. J. 453:137-145(2013).
RN [25]
RP FUNCTION IN SUMOYLATION OF SETX.
RX PubMed=24105744; DOI=10.1101/gad.224923.113;
RA Richard P., Feng S., Manley J.L.;
RT "A SUMO-dependent interaction between Senataxin and the exosome, disrupted
RT in the neurodegenerative disease AOA2, targets the exosome to sites of
RT transcription-induced DNA damage.";
RL Genes Dev. 27:2227-2232(2013).
RN [26]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-7 AND LYS-11, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25218447; DOI=10.1038/nsmb.2890;
RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M.,
RA Vertegaal A.C.;
RT "Uncovering global SUMOylation signaling networks in a site-specific
RT manner.";
RL Nat. Struct. Mol. Biol. 21:927-936(2014).
RN [27]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-11, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25114211; DOI=10.1073/pnas.1413825111;
RA Impens F., Radoshevich L., Cossart P., Ribet D.;
RT "Mapping of SUMO sites and analysis of SUMOylation changes induced by
RT external stimuli.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:12432-12437(2014).
RN [28]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-7 AND LYS-11, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25772364; DOI=10.1016/j.celrep.2015.02.033;
RA Hendriks I.A., Treffers L.W., Verlaan-de Vries M., Olsen J.V.,
RA Vertegaal A.C.;
RT "SUMO-2 orchestrates chromatin modifiers in response to DNA damage.";
RL Cell Rep. 10:1778-1791(2015).
RN [29]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-5; LYS-7 AND LYS-11, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25755297; DOI=10.1074/mcp.o114.044792;
RA Xiao Z., Chang J.G., Hendriks I.A., Sigurdsson J.O., Olsen J.V.,
RA Vertegaal A.C.;
RT "System-wide analysis of SUMOylation dynamics in response to replication
RT stress reveals novel small ubiquitin-like modified target proteins and
RT acceptor lysines relevant for genome stability.";
RL Mol. Cell. Proteomics 14:1419-1434(2015).
RN [30]
RP INTERACTION WITH GCNA.
RX PubMed=30914427; DOI=10.15252/embj.2019101496;
RA Borgermann N., Ackermann L., Schwertman P., Hendriks I.A., Thijssen K.,
RA Liu J.C., Lans H., Nielsen M.L., Mailand N.;
RT "SUMOylation promotes protective responses to DNA-protein cross-links.";
RL EMBO J. 38:0-0(2019).
RN [31]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-5; LYS-7; LYS-11 AND LYS-21, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [32]
RP X-RAY CRYSTALLOGRAPHY (1.2 ANGSTROMS) OF 9-93, AND SUBUNIT.
RX PubMed=15479240; DOI=10.1111/j.1432-1033.2004.04349.x;
RA Huang W.-C., Ko T.-P., Li S.S.-L., Wang A.H.-J.;
RT "Crystal structures of the human SUMO-2 protein at 1.6 A and 1.2 A
RT resolution: implication on the functional differences of SUMO proteins.";
RL Eur. J. Biochem. 271:4114-4122(2004).
RN [33]
RP STRUCTURE BY NMR OF 1-93.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of human SUMO-2 (SMT3B), a ubiquitin-like protein.";
RL Submitted (AUG-2005) to the PDB data bank.
RN [34]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 1-93 CONJUGATED TO TDG.
RX PubMed=16626738; DOI=10.1016/j.jmb.2006.03.036;
RA Baba D., Maita N., Jee J.-G., Uchimura Y., Saitoh H., Sugasawa K.,
RA Hanaoka F., Tochio H., Hiroaki H., Shirakawa M.;
RT "Crystal structure of SUMO-3-modified thymine-DNA glycosylase.";
RL J. Mol. Biol. 359:137-147(2006).
RN [35]
RP STRUCTURE BY NMR OF 1-95.
RA Chang C.K., Wang Y.H., Chung T.L., Chang C.F., Li S.S.L., Huang T.H.;
RT "Solution structure of human small ubiquitin-like modifier protein isoform
RT 2 (SUMO-2).";
RL Submitted (OCT-2006) to the PDB data bank.
RN [36]
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) IN COMPLEX WITH ZNF451 AND UBC9,
RP FUNCTION, PATHWAY, AND INTERACTION WITH ZNF451 AND UBC9.
RX PubMed=26524494; DOI=10.1038/nsmb.3116;
RA Cappadocia L., Pichler A., Lima C.D.;
RT "Structural basis for catalytic activation by the human ZNF451 SUMO E3
RT ligase.";
RL Nat. Struct. Mol. Biol. 22:968-975(2015).
CC -!- FUNCTION: Ubiquitin-like protein that can be covalently attached to
CC proteins as a monomer or as a lysine-linked polymer. Covalent
CC attachment via an isopeptide bond to its substrates requires prior
CC activation by the E1 complex SAE1-SAE2 and linkage to the E2 enzyme
CC UBE2I, and can be promoted by an E3 ligase such as PIAS1-4, RANBP2,
CC CBX4 or ZNF451 (PubMed:26524494). This post-translational modification
CC on lysine residues of proteins plays a crucial role in a number of
CC cellular processes such as nuclear transport, DNA replication and
CC repair, mitosis and signal transduction. Polymeric SUMO2 chains are
CC also susceptible to polyubiquitination which functions as a signal for
CC proteasomal degradation of modified proteins (PubMed:18408734,
CC PubMed:18538659, PubMed:21965678, PubMed:9556629). Plays a role in the
CC regulation of sumoylation status of SETX (PubMed:24105744).
CC {ECO:0000269|PubMed:18408734, ECO:0000269|PubMed:18538659,
CC ECO:0000269|PubMed:21965678, ECO:0000269|PubMed:24105744,
CC ECO:0000269|PubMed:26524494, ECO:0000269|PubMed:9556629}.
CC -!- SUBUNIT: Interacts with SAE2 and UBE2I. Interacts with ZNF451.
CC Identified in a complex with ZNF451 and UBE2I/UBC9, where one ZNF451
CC interacts with one UBE2I/UBC9 and two SUMO2 chains, one bound to the
CC UBE2I/UBC9 active site and the other to another region of the same
CC UBE2I/UBC9 molecule. Covalently attached to a number of proteins.
CC Interacts with PELP1. Interacts with USP25; the interaction sumoylates
CC USP25. Interacts with SIMC1, CASP8AP2, RNF111 AND SOBP (via SIM
CC domains). Interacts with MTA1 (PubMed:21965678). Interacts with HINT1
CC (By similarity). Interacts with GCNA (via SIM domains); this
CC interaction allows the GCNA recruitment to DPCs sites
CC (PubMed:30914427). {ECO:0000250|UniProtKB:P61957,
CC ECO:0000269|PubMed:12924945, ECO:0000269|PubMed:15479240,
CC ECO:0000269|PubMed:16567619, ECO:0000269|PubMed:18538659,
CC ECO:0000269|PubMed:21965678, ECO:0000269|PubMed:23086935,
CC ECO:0000269|PubMed:26524494, ECO:0000269|PubMed:30914427, ECO:0000305}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Epstein-barr virus BGLF4.
CC {ECO:0000269|PubMed:22398289}.
CC -!- INTERACTION:
CC P61956; P38398: BRCA1; NbExp=2; IntAct=EBI-473220, EBI-349905;
CC P61956; Q12873: CHD3; NbExp=3; IntAct=EBI-473220, EBI-523590;
CC P61956; Q8IX15-3: HOMEZ; NbExp=3; IntAct=EBI-473220, EBI-10172004;
CC P61956; P10242: MYB; NbExp=3; IntAct=EBI-473220, EBI-298355;
CC P61956; Q8IZL8: PELP1; NbExp=4; IntAct=EBI-473220, EBI-716449;
CC P61956; Q8N2W9: PIAS4; NbExp=3; IntAct=EBI-473220, EBI-473160;
CC P61956; Q9P0U3: SENP1; NbExp=6; IntAct=EBI-473220, EBI-2822935;
CC P61956; Q9HC62: SENP2; NbExp=5; IntAct=EBI-473220, EBI-714881;
CC P61956; P23497-2: SP100; NbExp=3; IntAct=EBI-473220, EBI-6589365;
CC P61956; Q92844: TANK; NbExp=3; IntAct=EBI-473220, EBI-356349;
CC P61956; Q13569: TDG; NbExp=2; IntAct=EBI-473220, EBI-348333;
CC P61956; P63279: UBE2I; NbExp=7; IntAct=EBI-473220, EBI-80168;
CC P61956; Q9UHP3: USP25; NbExp=6; IntAct=EBI-473220, EBI-2513462;
CC P61956; Q5W0Q7: USPL1; NbExp=2; IntAct=EBI-473220, EBI-2513899;
CC P61956; Q86T24: ZBTB33; NbExp=3; IntAct=EBI-473220, EBI-2515625;
CC P61956; O15060: ZBTB39; NbExp=3; IntAct=EBI-473220, EBI-9995672;
CC P61956; Q96IT1: ZNF496; NbExp=3; IntAct=EBI-473220, EBI-743906;
CC P61956; O88846: Rnf4; Xeno; NbExp=2; IntAct=EBI-473220, EBI-7258907;
CC P61956; Q6DRC5: uspl1; Xeno; NbExp=2; IntAct=EBI-473220, EBI-8018150;
CC -!- SUBCELLULAR LOCATION: Nucleus. Nucleus, PML body.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P61956-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P61956-2; Sequence=VSP_042351;
CC -!- TISSUE SPECIFICITY: Broadly expressed. {ECO:0000269|PubMed:9556629}.
CC -!- PTM: Polymeric chains can be formed through Lys-11 cross-linking.
CC Polymeric SUMO2 chains undergo 'Lys-6'-, 'Lys-11'-, 'Lys-48'- and 'Lys-
CC 63'-linked polyubiquitination by RNF4. {ECO:0000269|PubMed:18408734,
CC ECO:0000269|PubMed:23560854}.
CC -!- PTM: Cleavage of precursor form by SENP1 or SENP2 is necessary for
CC function. {ECO:0000269|PubMed:15487983}.
CC -!- PTM: Monoubiquitinated N-terminally by UBE2W, which primes it for RNF4-
CC dependent polyubiquitination by the UBE2V1-UBE2N heterodimer.
CC {ECO:0000269|PubMed:18408734, ECO:0000269|PubMed:23560854}.
CC -!- SIMILARITY: Belongs to the ubiquitin family. SUMO subfamily.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=SUMO protein entry;
CC URL="https://en.wikipedia.org/wiki/SUMO_protein";
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DR EMBL; L76416; AAD45399.1; -; mRNA.
DR EMBL; X99585; CAA67897.1; -; mRNA.
DR EMBL; AK311837; BAG34779.1; -; mRNA.
DR EMBL; AC022211; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471099; EAW89249.1; -; Genomic_DNA.
DR EMBL; BC008450; AAH08450.1; -; mRNA.
DR EMBL; BC016775; AAH16775.1; -; mRNA.
DR EMBL; BC022340; AAH22340.1; -; mRNA.
DR EMBL; BC062713; AAH62713.1; -; mRNA.
DR EMBL; BC068465; AAH68465.1; -; mRNA.
DR EMBL; BC070159; AAH70159.1; -; mRNA.
DR EMBL; BC071645; AAH71645.1; -; mRNA.
DR EMBL; BC071646; AAH71646.1; -; mRNA.
DR EMBL; BC107853; AAI07854.1; -; mRNA.
DR EMBL; BF978876; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS45773.1; -. [P61956-2]
DR CCDS; CCDS45774.1; -. [P61956-1]
DR PIR; JC4760; JC4760.
DR RefSeq; NP_001005849.1; NM_001005849.1. [P61956-2]
DR RefSeq; NP_008868.3; NM_006937.3. [P61956-1]
DR PDB; 1WM2; X-ray; 1.60 A; A=12-89.
DR PDB; 1WM3; X-ray; 1.20 A; A=17-88.
DR PDB; 1WZ0; NMR; -; A=1-91.
DR PDB; 2AWT; NMR; -; A=1-95.
DR PDB; 2CKH; X-ray; 3.20 A; B=15-93.
DR PDB; 2D07; X-ray; 2.10 A; B=1-93.
DR PDB; 2IO0; X-ray; 2.30 A; B=15-95.
DR PDB; 2IO3; X-ray; 3.20 A; B=15-93.
DR PDB; 2IYD; X-ray; 3.20 A; B=15-95.
DR PDB; 2N1W; NMR; -; A=1-93.
DR PDB; 2N9E; NMR; -; B=1-95.
DR PDB; 2RPQ; NMR; -; A=1-93.
DR PDB; 3UIN; X-ray; 2.60 A; B=14-93.
DR PDB; 3UIO; X-ray; 2.60 A; B=14-93.
DR PDB; 3ZO5; X-ray; 2.15 A; B=16-95.
DR PDB; 4BKG; X-ray; 2.11 A; A=12-93.
DR PDB; 4NPN; X-ray; 1.63 A; A=12-93.
DR PDB; 5D2M; X-ray; 2.40 A; B/E=15-93.
DR PDB; 5ELU; X-ray; 2.35 A; B=14-89.
DR PDB; 5EQL; X-ray; 2.49 A; B=14-89.
DR PDB; 5GHB; NMR; -; A=1-93.
DR PDB; 5GHC; NMR; -; A=1-93.
DR PDB; 6JXW; NMR; -; A=1-95.
DR PDB; 6JXX; NMR; -; A=1-95.
DR PDBsum; 1WM2; -.
DR PDBsum; 1WM3; -.
DR PDBsum; 1WZ0; -.
DR PDBsum; 2AWT; -.
DR PDBsum; 2CKH; -.
DR PDBsum; 2D07; -.
DR PDBsum; 2IO0; -.
DR PDBsum; 2IO3; -.
DR PDBsum; 2IYD; -.
DR PDBsum; 2N1W; -.
DR PDBsum; 2N9E; -.
DR PDBsum; 2RPQ; -.
DR PDBsum; 3UIN; -.
DR PDBsum; 3UIO; -.
DR PDBsum; 3ZO5; -.
DR PDBsum; 4BKG; -.
DR PDBsum; 4NPN; -.
DR PDBsum; 5D2M; -.
DR PDBsum; 5ELU; -.
DR PDBsum; 5EQL; -.
DR PDBsum; 5GHB; -.
DR PDBsum; 5GHC; -.
DR PDBsum; 6JXW; -.
DR PDBsum; 6JXX; -.
DR AlphaFoldDB; P61956; -.
DR BMRB; P61956; -.
DR SMR; P61956; -.
DR BioGRID; 112497; 581.
DR DIP; DIP-29253N; -.
DR ELM; P61956; -.
DR IntAct; P61956; 98.
DR MINT; P61956; -.
DR STRING; 9606.ENSP00000405965; -.
DR BindingDB; P61956; -.
DR ChEMBL; CHEMBL2146301; -.
DR iPTMnet; P61956; -.
DR PhosphoSitePlus; P61956; -.
DR BioMuta; SUMO2; -.
DR DMDM; 378405233; -.
DR EPD; P61956; -.
DR jPOST; P61956; -.
DR MassIVE; P61956; -.
DR MaxQB; P61956; -.
DR PaxDb; P61956; -.
DR PeptideAtlas; P61956; -.
DR PRIDE; P61956; -.
DR ProteomicsDB; 57342; -. [P61956-1]
DR ProteomicsDB; 57343; -. [P61956-2]
DR TopDownProteomics; P61956-1; -. [P61956-1]
DR TopDownProteomics; P61956-2; -. [P61956-2]
DR Antibodypedia; 32111; 1047 antibodies from 41 providers.
DR DNASU; 6613; -.
DR Ensembl; ENST00000314523.7; ENSP00000400886.2; ENSG00000188612.12. [P61956-2]
DR Ensembl; ENST00000420826.7; ENSP00000405965.2; ENSG00000188612.12. [P61956-1]
DR GeneID; 6613; -.
DR KEGG; hsa:6613; -.
DR MANE-Select; ENST00000420826.7; ENSP00000405965.2; NM_006937.4; NP_008868.3.
DR UCSC; uc002jne.4; human. [P61956-1]
DR CTD; 6613; -.
DR DisGeNET; 6613; -.
DR GeneCards; SUMO2; -.
DR HGNC; HGNC:11125; SUMO2.
DR HPA; ENSG00000188612; Low tissue specificity.
DR MIM; 603042; gene.
DR neXtProt; NX_P61956; -.
DR OpenTargets; ENSG00000188612; -.
DR PharmGKB; PA134914683; -.
DR VEuPathDB; HostDB:ENSG00000188612; -.
DR eggNOG; KOG1769; Eukaryota.
DR GeneTree; ENSGT00950000182895; -.
DR HOGENOM; CLU_148322_2_1_1; -.
DR InParanoid; P61956; -.
DR OMA; AYCDRVG; -.
DR PhylomeDB; P61956; -.
DR TreeFam; TF315116; -.
DR PathwayCommons; P61956; -.
DR Reactome; R-HSA-196791; Vitamin D (calciferol) metabolism.
DR Reactome; R-HSA-3065676; SUMO is conjugated to E1 (UBA2:SAE1).
DR Reactome; R-HSA-3065678; SUMO is transferred from E1 to E2 (UBE2I, UBC9).
DR Reactome; R-HSA-3065679; SUMO is proteolytically processed.
DR Reactome; R-HSA-3108214; SUMOylation of DNA damage response and repair proteins.
DR Reactome; R-HSA-3232118; SUMOylation of transcription factors.
DR Reactome; R-HSA-3899300; SUMOylation of transcription cofactors.
DR Reactome; R-HSA-4085377; SUMOylation of SUMOylation proteins.
DR Reactome; R-HSA-4090294; SUMOylation of intracellular receptors.
DR Reactome; R-HSA-4551638; SUMOylation of chromatin organization proteins.
DR Reactome; R-HSA-4570464; SUMOylation of RNA binding proteins.
DR Reactome; R-HSA-4615885; SUMOylation of DNA replication proteins.
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 SignaLink; P61956; -.
DR BioGRID-ORCS; 6613; 453 hits in 1014 CRISPR screens.
DR ChiTaRS; SUMO2; human.
DR EvolutionaryTrace; P61956; -.
DR GeneWiki; SUMO2; -.
DR GenomeRNAi; 6613; -.
DR Pharos; P61956; Tbio.
DR PRO; PR:P61956; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P61956; protein.
DR Bgee; ENSG00000188612; Expressed in ganglionic eminence and 208 other tissues.
DR ExpressionAtlas; P61956; baseline and differential.
DR Genevisible; P61956; HS.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0016605; C:PML body; IDA:UniProtKB.
DR GO; GO:0031386; F:protein tag; IBA:GO_Central.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0044389; F:ubiquitin-like protein ligase binding; IBA:GO_Central.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR GO; GO:0016925; P:protein sumoylation; IDA:UniProtKB.
DR IDEAL; IID00376; -.
DR InterPro; IPR022617; Rad60/SUMO-like_dom.
DR InterPro; IPR000626; Ubiquitin-like_dom.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR Pfam; PF11976; Rad60-SLD; 1.
DR SMART; SM00213; UBQ; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR PROSITE; PS50053; UBIQUITIN_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Host-virus interaction;
KW Isopeptide bond; Nucleus; Reference proteome; Ubl conjugation;
KW Ubl conjugation pathway.
FT CHAIN 1..93
FT /note="Small ubiquitin-related modifier 2"
FT /id="PRO_0000035949"
FT PROPEP 94..95
FT /evidence="ECO:0000269|PubMed:15487983"
FT /id="PRO_0000035950"
FT DOMAIN 16..95
FT /note="Ubiquitin-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00214"
FT MOD_RES 11
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT CROSSLNK 1
FT /note="Peptide (Met-Gly) (interchain with G-Cter in
FT ubiquitin)"
FT /evidence="ECO:0000269|PubMed:23560854"
FT CROSSLNK 5
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25755297,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 7
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:25755297, ECO:0007744|PubMed:25772364,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 11
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT CROSSLNK 11
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1); alternate"
FT /evidence="ECO:0007744|PubMed:25114211"
FT CROSSLNK 11
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:25755297, ECO:0007744|PubMed:25772364,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 11
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000269|PubMed:18408734"
FT CROSSLNK 21
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 93
FT /note="Glycyl lysine isopeptide (Gly-Lys) (interchain with
FT K-? in acceptor proteins)"
FT VAR_SEQ 51..74
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_042351"
FT VARIANT 16
FT /note="D -> N (in dbSNP:rs17850328)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_047508"
FT MUTAGEN 11
FT /note="K->R: Abolishes the formation of poly(SUMO) chains."
FT /evidence="ECO:0000269|PubMed:11451954"
FT MUTAGEN 33
FT /note="K->E: Significantly impairs sumoylation of MTA1."
FT /evidence="ECO:0000269|PubMed:21965678"
FT MUTAGEN 35
FT /note="K->E: Significantly impairs sumoylation of MTA1."
FT /evidence="ECO:0000269|PubMed:21965678"
FT MUTAGEN 42
FT /note="K->E: Significantly impairs sumoylation of MTA1."
FT /evidence="ECO:0000269|PubMed:21965678"
FT STRAND 3..5
FT /evidence="ECO:0007829|PDB:2N1W"
FT STRAND 11..13
FT /evidence="ECO:0007829|PDB:2RPQ"
FT TURN 14..16
FT /evidence="ECO:0007829|PDB:2RPQ"
FT STRAND 18..23
FT /evidence="ECO:0007829|PDB:1WM3"
FT TURN 25..27
FT /evidence="ECO:0007829|PDB:2CKH"
FT STRAND 29..34
FT /evidence="ECO:0007829|PDB:1WM3"
FT STRAND 36..38
FT /evidence="ECO:0007829|PDB:6JXX"
FT HELIX 41..51
FT /evidence="ECO:0007829|PDB:1WM3"
FT TURN 55..57
FT /evidence="ECO:0007829|PDB:1WM3"
FT STRAND 59..62
FT /evidence="ECO:0007829|PDB:1WM3"
FT STRAND 65..67
FT /evidence="ECO:0007829|PDB:2RPQ"
FT TURN 73..77
FT /evidence="ECO:0007829|PDB:1WM3"
FT STRAND 82..87
FT /evidence="ECO:0007829|PDB:1WM3"
FT STRAND 90..93
FT /evidence="ECO:0007829|PDB:2AWT"
SQ SEQUENCE 95 AA; 10871 MW; F8F0426849BEF08B CRC64;
MADEKPKEGV KTENNDHINL KVAGQDGSVV QFKIKRHTPL SKLMKAYCER QGLSMRQIRF
RFDGQPINET DTPAQLEMED EDTIDVFQQQ TGGVY
