UBE3A_HUMAN
ID UBE3A_HUMAN Reviewed; 875 AA.
AC Q05086; A8K8Z9; P78355; Q93066; Q9UEP4; Q9UEP5; Q9UEP6; Q9UEP7; Q9UEP8;
AC Q9UEP9;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2008, sequence version 4.
DT 03-AUG-2022, entry version 218.
DE RecName: Full=Ubiquitin-protein ligase E3A;
DE EC=2.3.2.26 {ECO:0000269|PubMed:24273172};
DE AltName: Full=E6AP ubiquitin-protein ligase {ECO:0000303|PubMed:17108031};
DE AltName: Full=HECT-type ubiquitin transferase E3A;
DE AltName: Full=Human papillomavirus E6-associated protein {ECO:0000303|PubMed:8380895};
DE AltName: Full=Oncogenic protein-associated protein E6-AP {ECO:0000303|PubMed:8380895};
DE AltName: Full=Renal carcinoma antigen NY-REN-54;
GN Name=UBE3A {ECO:0000312|HGNC:HGNC:12496};
GN Synonyms=E6AP {ECO:0000303|PubMed:17108031},
GN EPVE6AP {ECO:0000303|PubMed:8380895}, HPVE6A {ECO:0000303|PubMed:8380895};
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 [GENOMIC DNA / MRNA] (ISOFORMS I; II AND III), AND
RP VARIANT GLY-290.
RC TISSUE=Keratinocyte;
RX PubMed=9143503; DOI=10.1006/geno.1997.4617;
RA Yamamoto Y., Huibregtse J.M., Howley P.M.;
RT "The human E6-AP gene (UBE3A) encodes three potential protein isoforms
RT generated by differential splicing.";
RL Genomics 41:263-266(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM I).
RC TISSUE=Fetal brain;
RX PubMed=8988171; DOI=10.1038/ng0197-70;
RA Kishino T., Lalande M., Wagstaff J.;
RT "UBE3A/E6-AP mutations cause Angelman syndrome.";
RL Nat. Genet. 15:70-73(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM I), AND VARIANTS TYR-44 AND
RP THR-201.
RX PubMed=8988172; DOI=10.1038/ng0197-74;
RA Matsuura T., Sutcliffe J.S., Fang P., Galjaard R.-J., Jiang Y.-H.,
RA Benton C.S., Rommens J.M., Beaudet A.L.;
RT "De novo truncating mutations in E6-AP ubiquitin-protein ligase gene
RT (UBE3A) in Angelman syndrome.";
RL Nat. Genet. 15:74-77(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM III).
RC TISSUE=Testis;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 11-875, PARTIAL PROTEIN SEQUENCE, FUNCTION
RP (MICROBIAL INFECTION), AND VARIANT GLY-290.
RC TISSUE=Keratinocyte;
RX PubMed=8380895; DOI=10.1128/mcb.13.2.775-784.1993;
RA Huibregtse J.M., Scheffner M., Howley P.M.;
RT "Cloning and expression of the cDNA for E6-AP, a protein that mediates the
RT interaction of the human papillomavirus E6 oncoprotein with p53.";
RL Mol. Cell. Biol. 13:775-784(1993).
RN [8]
RP CHARACTERIZATION.
RX PubMed=9688277; DOI=10.1046/j.1432-1327.1998.2540643.x;
RA Nuber U., Schwarz S.E., Scheffner M.;
RT "The ubiquitin-protein ligase E6-associated protein (E6-AP) serves as its
RT own substrate.";
RL Eur. J. Biochem. 254:643-649(1998).
RN [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 25-787, AND VARIANT GLY-290.
RA Hennies H.C., Buerger J., Sperling K., Reis A.;
RT "Mutations in the E6-AP gene (UBE3A) in patients with Angelman syndrome.";
RL Submitted (AUG-1997) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP IDENTIFICATION AS A RENAL CANCER ANTIGEN.
RC TISSUE=Renal cell carcinoma;
RX PubMed=10508479;
RX DOI=10.1002/(sici)1097-0215(19991112)83:4<456::aid-ijc4>3.0.co;2-5;
RA Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H.,
RA Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T.,
RA Old L.J.;
RT "Antigens recognized by autologous antibody in patients with renal-cell
RT carcinoma.";
RL Int. J. Cancer 83:456-464(1999).
RN [11]
RP FUNCTION.
RX PubMed=10373495; DOI=10.1074/jbc.274.26.18785;
RA Kumar S., Talis A.L., Howley P.M.;
RT "Identification of HHR23A as a substrate for E6-associated protein-mediated
RT ubiquitination.";
RL J. Biol. Chem. 274:18785-18792(1999).
RN [12]
RP INTERACTION WITH UBQLN1 AND UBQLN2.
RX PubMed=10983987; DOI=10.1016/s1097-2765(00)00040-x;
RA Kleijnen M.F., Shih A.H., Zhou P., Kumar S., Soccio R.E., Kedersha N.L.,
RA Gill G., Howley P.M.;
RT "The hPLIC proteins may provide a link between the ubiquitination machinery
RT and the proteasome.";
RL Mol. Cell 6:409-419(2000).
RN [13]
RP INTERACTION WITH BPY2.
RX PubMed=12207887; DOI=10.1016/s0006-291x(02)02040-5;
RA Wong E.Y., Tse J.Y., Yao K.M., Tam P.C., Yeung W.S.;
RT "VCY2 protein interacts with the HECT domain of ubiquitin-protein ligase
RT E3A.";
RL Biochem. Biophys. Res. Commun. 296:1104-1111(2002).
RN [14]
RP FUNCTION, AND INTERACTION WITH ESR1 AND WBP2.
RX PubMed=16772533; DOI=10.1210/me.2005-0533;
RA Dhananjayan S.C., Ramamoorthy S., Khan O.Y., Ismail A., Sun J.,
RA Slingerland J., O'Malley B.W., Nawaz Z.;
RT "WW domain binding protein-2, an E6-associated protein interacting protein,
RT acts as a coactivator of estrogen and progesterone receptors.";
RL Mol. Endocrinol. 20:2343-2354(2006).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17323924; DOI=10.1021/bi061994u;
RA Wang X., Chen C.-F., Baker P.R., Chen P.-L., Kaiser P., Huang L.;
RT "Mass spectrometric characterization of the affinity-purified human 26S
RT proteasome complex.";
RL Biochemistry 46:3553-3565(2007).
RN [16]
RP INTERACTION WITH HCV CORE PROTEIN.
RX PubMed=17108031; DOI=10.1128/jvi.01684-06;
RA Shirakura M., Murakami K., Ichimura T., Suzuki R., Shimoji T., Fukuda K.,
RA Abe K., Sato S., Fukasawa M., Yamakawa Y., Nishijima M., Moriishi K.,
RA Matsuura Y., Wakita T., Suzuki T., Howley P.M., Miyamura T., Shoji I.;
RT "E6AP ubiquitin ligase mediates ubiquitylation and degradation of hepatitis
RT C virus core protein.";
RL J. Virol. 81:1174-1185(2007).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-218, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [18]
RP FUNCTION.
RX PubMed=19325566; DOI=10.1038/cdd.2009.31;
RA Louria-Hayon I., Alsheich-Bartok O., Levav-Cohen Y., Silberman I.,
RA Berger M., Grossman T., Matentzoglu K., Jiang Y.H., Muller S.,
RA Scheffner M., Haupt S., Haupt Y.;
RT "E6AP promotes the degradation of the PML tumor suppressor.";
RL Cell Death Differ. 16:1156-1166(2009).
RN [19]
RP FUNCTION.
RX PubMed=19233847; DOI=10.1074/jbc.m806804200;
RA Mishra A., Godavarthi S.K., Maheshwari M., Goswami A., Jana N.R.;
RT "The ubiquitin ligase E6-AP is induced and recruited to aggresomes in
RT response to proteasome inhibition and may be involved in the ubiquitination
RT of Hsp70-bound misfolded proteins.";
RL J. Biol. Chem. 284:10537-10545(2009).
RN [20]
RP FUNCTION.
RX PubMed=19204938; DOI=10.1002/jcb.22096;
RA Shimoji T., Murakami K., Sugiyama Y., Matsuda M., Inubushi S., Nasu J.,
RA Shirakura M., Suzuki T., Wakita T., Kishino T., Hotta H., Miyamura T.,
RA Shoji I.;
RT "Identification of annexin A1 as a novel substrate for E6AP-mediated
RT ubiquitylation.";
RL J. Cell. Biochem. 106:1123-1135(2009).
RN [21]
RP FUNCTION.
RX PubMed=19591933; DOI=10.1016/j.nbd.2009.06.010;
RA Mishra A., Godavarthi S.K., Jana N.R.;
RT "UBE3A/E6-AP regulates cell proliferation by promoting proteasomal
RT degrADation of p27.";
RL Neurobiol. Dis. 36:26-34(2009).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-218, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [24]
RP INTERACTION WITH WBP2.
RX PubMed=21642474; DOI=10.1096/fj.10-169136;
RA Lim S.K., Orhant-Prioux M., Toy W., Tan K.Y., Lim Y.P.;
RT "Tyrosine phosphorylation of transcriptional coactivator WW-domain binding
RT protein 2 regulates estrogen receptor alpha function in breast cancer via
RT the Wnt pathway.";
RL FASEB J. 25:3004-3018(2011).
RN [25]
RP FUNCTION, AND INTERACTION WITH HIF1AN; MAPK6; NEURL4 AND PSMD4.
RX PubMed=22645313; DOI=10.1128/mcb.00201-12;
RA Martinez-Noel G., Galligan J.T., Sowa M.E., Arndt V., Overton T.M.,
RA Harper J.W., Howley P.M.;
RT "Identification and proteomic analysis of distinct UBE3A/E6AP protein
RT complexes.";
RL Mol. Cell. Biol. 32:3095-3106(2012).
RN [26]
RP PHOSPHORYLATION AT TYR-659.
RX PubMed=23581475; DOI=10.1021/bi301710c;
RA Chan A.L., Grossman T., Zuckerman V., Campigli Di Giammartino D.,
RA Moshel O., Scheffner M., Monahan B., Pilling P., Jiang Y.H., Haupt S.,
RA Schueler-Furman O., Haupt Y.;
RT "c-Abl phosphorylates E6AP and regulates its E3 ubiquitin ligase
RT activity.";
RL Biochemistry 52:3119-3129(2013).
RN [27]
RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AND MUTAGENESIS OF PHE-750.
RX PubMed=24273172; DOI=10.1074/jbc.m113.517805;
RA Ronchi V.P., Klein J.M., Edwards D.J., Haas A.L.;
RT "The active form of E6-associated protein (E6AP)/UBE3A ubiquitin ligase is
RT an oligomer.";
RL J. Biol. Chem. 289:1033-1048(2014).
RN [28]
RP FUNCTION, AND INTERACTION WITH ARNTL.
RX PubMed=24728990; DOI=10.1093/nar/gku225;
RA Gossan N.C., Zhang F., Guo B., Jin D., Yoshitane H., Yao A., Glossop N.,
RA Zhang Y.Q., Fukada Y., Meng Q.J.;
RT "The E3 ubiquitin ligase UBE3A is an integral component of the molecular
RT circadian clock through regulating the BMAL1 transcription factor.";
RL Nucleic Acids Res. 42:5765-5775(2014).
RN [29]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 495-852 IN COMPLEX WITH UBE2L3.
RX PubMed=10558980; DOI=10.1126/science.286.5443.1321;
RA Huang L., Kinnucan E., Wang G., Beaudenon S., Howley P.M., Huibregtse J.M.,
RA Pavletich N.P.;
RT "Structure of an E6AP-UbcH7 complex: insights into ubiquitination by the
RT E2-E3 enzyme cascade.";
RL Science 286:1321-1326(1999).
RN [30]
RP STRUCTURE BY NMR OF 401-418.
RX PubMed=11170455; DOI=10.1021/bi0019592;
RA Be X., Hong Y., Wei J., Androphy E.J., Chen J.J., Baleja J.D.;
RT "Solution structure determination and mutational analysis of the
RT papillomavirus E6 interacting peptide of E6AP.";
RL Biochemistry 40:1293-1299(2001).
RN [31]
RP STRUCTURE BY NMR OF 24-87, AND ZINC-FINGER.
RX PubMed=21947926; DOI=10.1007/s10858-011-9552-y;
RA Lemak A., Yee A., Bezsonova I., Dhe-Paganon S., Arrowsmith C.H.;
RT "Zn-binding AZUL domain of human ubiquitin protein ligase Ube3A.";
RL J. Biomol. NMR 51:185-190(2011).
RN [32]
RP VARIANT AS ILE-826 INS, VARIANTS HIS-62; THR-201 AND PRO-372, AND
RP INVOLVEMENT IN AS.
RX PubMed=9585605; DOI=10.1086/301877;
RA Malzac P., Webber H., Moncla A., Graham J.M. Jr., Kukolich M., Williams C.,
RA Pagon R.A., Ramsdell L.A., Kishino T., Wagstaff J.;
RT "Mutation analysis of UBE3A in Angelman syndrome patients.";
RL Am. J. Hum. Genet. 62:1353-1360(1998).
RN [33]
RP VARIANTS AS LYS-129; VAL-235; GLN-260; HIS-260; TRP-286; PRO-458; LEU-481;
RP PRO-500; ARG-568; LYS-589; GLN-607; ILE-679; CYS-713 AND LEU-850, AND
RP VARIANTS ARG-140; GLY-156; THR-293; THR-358; ILE-501; GLU-611; PRO-611;
RP ARG-696 AND ILE-785.
RX PubMed=25212744; DOI=10.1002/humu.22687;
RA Sadikovic B., Fernandes P., Zhang V.W., Ward P.A., Miloslavskaya I.,
RA Rhead W., Rosenbaum R., Gin R., Roa B., Fang P.;
RT "Mutation update for UBE3A variants in Angelman syndrome.";
RL Hum. Mutat. 35:1407-1417(2014).
CC -!- FUNCTION: E3 ubiquitin-protein ligase which accepts ubiquitin from an
CC E2 ubiquitin-conjugating enzyme in the form of a thioester and
CC transfers it to its substrates (PubMed:10373495, PubMed:16772533,
CC PubMed:19204938, PubMed:19233847, PubMed:19325566, PubMed:19591933,
CC PubMed:22645313, PubMed:24273172, PubMed:24728990). Several substrates
CC have been identified including the ARNTL/BMAL1, ARC, RAD23A and RAD23B,
CC MCM7 (which is involved in DNA replication), annexin A1, the PML tumor
CC suppressor, and the cell cycle regulator CDKN1B (PubMed:10373495,
CC PubMed:19204938, PubMed:19325566, PubMed:19591933, PubMed:22645313,
CC PubMed:24728990). Additionally, may function as a cellular quality
CC control ubiquitin ligase by helping the degradation of the cytoplasmic
CC misfolded proteins (PubMed:19233847). Finally, UBE3A also promotes its
CC own degradation in vivo. Plays an important role in the regulation of
CC the circadian clock: involved in the ubiquitination of the core clock
CC component ARNTL/BMAL1, leading to its proteasomal degradation
CC (PubMed:24728990). Acts as transcriptional coactivator of progesterone
CC receptor PGR upon progesterone hormone activation (PubMed:16772533).
CC Acts as a regulator of synaptic development by mediating ubiquitination
CC and degradation of ARC (By similarity). Synergizes with WBP2 in
CC enhancing PGR activity (PubMed:16772533).
CC {ECO:0000250|UniProtKB:O08759, ECO:0000269|PubMed:10373495,
CC ECO:0000269|PubMed:16772533, ECO:0000269|PubMed:19204938,
CC ECO:0000269|PubMed:19233847, ECO:0000269|PubMed:19325566,
CC ECO:0000269|PubMed:19591933, ECO:0000269|PubMed:22645313,
CC ECO:0000269|PubMed:24273172, ECO:0000269|PubMed:24728990}.
CC -!- FUNCTION: (Microbial infection) Catalyzes the high-risk human papilloma
CC virus E6-mediated ubiquitination of p53/TP53, contributing to the
CC neoplastic progression of cells infected by these viruses.
CC {ECO:0000269|PubMed:8380895}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.26; Evidence={ECO:0000269|PubMed:24273172};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:24273172}.
CC -!- SUBUNIT: The active form is probably a homotrimer. Binds UBQLN1 and
CC UBQLN2. Interacts with the 26S proteasome. Interacts with BPY2.
CC Interacts with HIF1AN, MAPK6 AND NEURL4; interaction with MAPK6 may be
CC mediated by NEURL4. Interacts with the proteasomal subunit PSMD4.
CC Interacts with ESR1 and WBP2 (PubMed:16772533, PubMed:21642474).
CC Interacts with ARNTL/BMAL1 (PubMed:24728990). Interacts with ARC (By
CC similarity). {ECO:0000250|UniProtKB:O08759,
CC ECO:0000269|PubMed:10558980, ECO:0000269|PubMed:10983987,
CC ECO:0000269|PubMed:12207887, ECO:0000269|PubMed:16772533,
CC ECO:0000269|PubMed:17108031, ECO:0000269|PubMed:21642474,
CC ECO:0000269|PubMed:22645313, ECO:0000269|PubMed:24273172,
CC ECO:0000269|PubMed:24728990}.
CC -!- SUBUNIT: (Microbial infection) Interacts with HCV core protein and
CC targets it to degradation. {ECO:0000269|PubMed:17108031}.
CC -!- SUBUNIT: (Microbial infection) Interacts with the E6 protein of the
CC cancer-associated human papillomavirus types 16 and 18. The E6/E6-AP
CC complex binds to and targets the p53/TP53 tumor-suppressor protein for
CC ubiquitin-mediated proteolysis. {ECO:0000269|PubMed:17108031}.
CC -!- INTERACTION:
CC Q05086; Q14566: MCM6; NbExp=6; IntAct=EBI-954357, EBI-374900;
CC Q05086; Q06413: MEF2C; NbExp=3; IntAct=EBI-954357, EBI-2684075;
CC Q05086; P55036: PSMD4; NbExp=3; IntAct=EBI-954357, EBI-359318;
CC Q05086; P17735: TAT; NbExp=3; IntAct=EBI-954357, EBI-12046643;
CC Q05086; P04637: TP53; NbExp=6; IntAct=EBI-954357, EBI-366083;
CC Q05086; P03126: E6; Xeno; NbExp=10; IntAct=EBI-954357, EBI-1177242;
CC Q05086; P04019: E6; Xeno; NbExp=5; IntAct=EBI-954357, EBI-1177232;
CC Q05086; P06462: E6; Xeno; NbExp=2; IntAct=EBI-954357, EBI-7069993;
CC Q05086; P06463: E6; Xeno; NbExp=7; IntAct=EBI-954357, EBI-1186926;
CC Q05086; P06931: E6; Xeno; NbExp=2; IntAct=EBI-954357, EBI-7281937;
CC Q05086; P36799: E6; Xeno; NbExp=2; IntAct=EBI-954357, EBI-7363822;
CC Q05086; Q77E16: E6; Xeno; NbExp=3; IntAct=EBI-954357, EBI-7011359;
CC Q05086-2; Q9NZD4: AHSP; NbExp=3; IntAct=EBI-10175863, EBI-720250;
CC Q05086-2; Q8TDY4: ASAP3; NbExp=3; IntAct=EBI-10175863, EBI-2609717;
CC Q05086-2; Q7Z3C6: ATG9A; NbExp=3; IntAct=EBI-10175863, EBI-727146;
CC Q05086-2; Q99613: EIF3C; NbExp=2; IntAct=EBI-10175863, EBI-353741;
CC Q05086-2; O95714: HERC2; NbExp=5; IntAct=EBI-10175863, EBI-1058922;
CC Q05086-2; Q2WGJ6: KLHL38; NbExp=3; IntAct=EBI-10175863, EBI-6426443;
CC Q05086-2; Q14566: MCM6; NbExp=3; IntAct=EBI-10175863, EBI-374900;
CC Q05086-2; P55036: PSMD4; NbExp=3; IntAct=EBI-10175863, EBI-359318;
CC Q05086-2; A1L4G7: TAT; NbExp=3; IntAct=EBI-10175863, EBI-10223561;
CC Q05086-2; Q5U5U6: UBB; NbExp=3; IntAct=EBI-10175863, EBI-1642104;
CC Q05086-2; B3KPL7; NbExp=3; IntAct=EBI-10175863, EBI-10175860;
CC Q05086-3; O75874: IDH1; NbExp=3; IntAct=EBI-11026619, EBI-715695;
CC Q05086-3; Q9Y4F3: MARF1; NbExp=3; IntAct=EBI-11026619, EBI-5235902;
CC Q05086-3; Q92570: NR4A3; NbExp=3; IntAct=EBI-11026619, EBI-13644623;
CC Q05086-3; Q6NTF9-3: RHBDD2; NbExp=3; IntAct=EBI-11026619, EBI-17589229;
CC Q05086-3; Q92966: SNAPC3; NbExp=3; IntAct=EBI-11026619, EBI-1760638;
CC Q05086-3; P17735: TAT; NbExp=11; IntAct=EBI-11026619, EBI-12046643;
CC Q05086-3; Q9NUH8: TMEM14B; NbExp=3; IntAct=EBI-11026619, EBI-8638294;
CC Q05086-3; P0CG48: UBC; NbExp=3; IntAct=EBI-11026619, EBI-3390054;
CC Q05086-3; A0A2K7P776; NbExp=3; IntAct=EBI-11026619, EBI-18894179;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O08759}. Nucleus
CC {ECO:0000250|UniProtKB:O08759}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=II;
CC IsoId=Q05086-1; Sequence=Displayed;
CC Name=I;
CC IsoId=Q05086-2; Sequence=VSP_006705;
CC Name=III;
CC IsoId=Q05086-3; Sequence=VSP_006706;
CC -!- PTM: Phosphorylation at Tyr-659 by ABL1 impairs E3 ligase activity and
CC protects p53/TP53 from degradation in (HPV)-infected cells.
CC {ECO:0000269|PubMed:23581475}.
CC -!- DISEASE: Angelman syndrome (AS) [MIM:105830]: A neurodevelopmental
CC disorder characterized by severe motor and intellectual retardation,
CC ataxia, frequent jerky limb movements and flapping of the arms and
CC hands, hypotonia, seizures, absence of speech, frequent smiling and
CC episodes of paroxysmal laughter, open-mouthed expression revealing the
CC tongue. {ECO:0000269|PubMed:25212744, ECO:0000269|PubMed:9585605}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- MISCELLANEOUS: A cysteine residue is required for ubiquitin-thioester
CC formation.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/UBE3AID42756ch15q11.html";
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DR EMBL; X98021; CAA66653.1; -; Genomic_DNA.
DR EMBL; X98027; CAA66653.1; JOINED; Genomic_DNA.
DR EMBL; X98022; CAA66653.1; JOINED; Genomic_DNA.
DR EMBL; X98023; CAA66653.1; JOINED; Genomic_DNA.
DR EMBL; X98024; CAA66653.1; JOINED; Genomic_DNA.
DR EMBL; X98025; CAA66653.1; JOINED; Genomic_DNA.
DR EMBL; X98026; CAA66653.1; JOINED; Genomic_DNA.
DR EMBL; X98028; CAA66653.1; JOINED; Genomic_DNA.
DR EMBL; X98029; CAA66653.1; JOINED; Genomic_DNA.
DR EMBL; X98030; CAA66653.1; JOINED; Genomic_DNA.
DR EMBL; X98031; CAA66654.1; -; mRNA.
DR EMBL; X98032; CAA66655.1; -; mRNA.
DR EMBL; X98033; CAA66656.1; -; mRNA.
DR EMBL; AC100774; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AK292514; BAF85203.1; -; mRNA.
DR EMBL; AC124997; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471151; EAW57645.1; -; Genomic_DNA.
DR EMBL; L07557; AAA35542.1; -; mRNA.
DR EMBL; AF016708; AAB69154.1; -; Genomic_DNA.
DR EMBL; AF016703; AAB69154.1; JOINED; Genomic_DNA.
DR EMBL; AF016704; AAB69154.1; JOINED; Genomic_DNA.
DR EMBL; AF016705; AAB69154.1; JOINED; Genomic_DNA.
DR EMBL; AF016706; AAB69154.1; JOINED; Genomic_DNA.
DR EMBL; AF016707; AAB69154.1; JOINED; Genomic_DNA.
DR EMBL; U84404; AAB49301.1; -; mRNA.
DR EMBL; AJ001107; CAA04534.1; -; Genomic_DNA.
DR EMBL; AJ001108; CAA04535.1; -; Genomic_DNA.
DR EMBL; AJ001109; CAA04536.1; -; Genomic_DNA.
DR EMBL; AJ001110; CAA04537.1; -; Genomic_DNA.
DR EMBL; AJ001111; CAA04538.1; -; Genomic_DNA.
DR EMBL; AJ001112; CAA04539.1; -; Genomic_DNA.
DR CCDS; CCDS32177.1; -. [Q05086-2]
DR CCDS; CCDS45191.1; -. [Q05086-3]
DR CCDS; CCDS45192.1; -. [Q05086-1]
DR CCDS; CCDS86436.1; -. [Q05086-2]
DR RefSeq; NP_000453.2; NM_000462.3. [Q05086-1]
DR RefSeq; NP_570853.1; NM_130838.1. [Q05086-2]
DR RefSeq; NP_570854.1; NM_130839.2. [Q05086-3]
DR RefSeq; XP_005268324.1; XM_005268267.4.
DR RefSeq; XP_005268325.1; XM_005268268.4.
DR RefSeq; XP_005268326.1; XM_005268269.4.
DR RefSeq; XP_005268327.1; XM_005268270.4.
DR RefSeq; XP_005268328.1; XM_005268271.4.
DR RefSeq; XP_006720738.1; XM_006720675.3.
DR RefSeq; XP_006720739.1; XM_006720676.3.
DR RefSeq; XP_011520296.1; XM_011521994.2.
DR RefSeq; XP_011520297.1; XM_011521995.2. [Q05086-1]
DR RefSeq; XP_016878033.1; XM_017022544.1.
DR RefSeq; XP_016878034.1; XM_017022545.1.
DR RefSeq; XP_016878035.1; XM_017022546.1.
DR RefSeq; XP_016878036.1; XM_017022547.1. [Q05086-3]
DR RefSeq; XP_016878037.1; XM_017022548.1. [Q05086-3]
DR RefSeq; XP_016878038.1; XM_017022549.1.
DR RefSeq; XP_016878039.1; XM_017022550.1. [Q05086-3]
DR RefSeq; XP_016878040.1; XM_017022551.1.
DR RefSeq; XP_016878041.1; XM_017022552.1.
DR RefSeq; XP_016878042.1; XM_017022553.1.
DR RefSeq; XP_016878043.1; XM_017022554.1.
DR RefSeq; XP_016878044.1; XM_017022555.1.
DR PDB; 1C4Z; X-ray; 2.60 A; A/B/C=518-875.
DR PDB; 1D5F; X-ray; 2.80 A; A/B/C=518-875.
DR PDB; 1EQX; NMR; -; A=401-418.
DR PDB; 2KR1; NMR; -; A=24-87.
DR PDB; 4GIZ; X-ray; 2.55 A; A/B=403-414.
DR PDB; 4XR8; X-ray; 2.25 A; A/B=406-417.
DR PDB; 6SJV; X-ray; 2.03 A; A=403-417.
DR PDB; 6SLM; X-ray; 2.80 A; A=403-417.
DR PDB; 6TGK; X-ray; 1.30 A; C=765-869.
DR PDB; 6U19; NMR; -; B=24-87.
DR PDBsum; 1C4Z; -.
DR PDBsum; 1D5F; -.
DR PDBsum; 1EQX; -.
DR PDBsum; 2KR1; -.
DR PDBsum; 4GIZ; -.
DR PDBsum; 4XR8; -.
DR PDBsum; 6SJV; -.
DR PDBsum; 6SLM; -.
DR PDBsum; 6TGK; -.
DR PDBsum; 6U19; -.
DR AlphaFoldDB; Q05086; -.
DR BMRB; Q05086; -.
DR SMR; Q05086; -.
DR BioGRID; 113185; 398.
DR CORUM; Q05086; -.
DR DIP; DIP-6002N; -.
DR IntAct; Q05086; 159.
DR MINT; Q05086; -.
DR STRING; 9606.ENSP00000232165; -.
DR MoonDB; Q05086; Predicted.
DR GlyGen; Q05086; 1 site, 2 O-linked glycans (1 site).
DR iPTMnet; Q05086; -.
DR MetOSite; Q05086; -.
DR PhosphoSitePlus; Q05086; -.
DR SwissPalm; Q05086; -.
DR BioMuta; UBE3A; -.
DR DMDM; 215274240; -.
DR EPD; Q05086; -.
DR jPOST; Q05086; -.
DR MassIVE; Q05086; -.
DR MaxQB; Q05086; -.
DR PaxDb; Q05086; -.
DR PeptideAtlas; Q05086; -.
DR PRIDE; Q05086; -.
DR ProteomicsDB; 58306; -. [Q05086-1]
DR ProteomicsDB; 58307; -. [Q05086-2]
DR ProteomicsDB; 58308; -. [Q05086-3]
DR Antibodypedia; 9118; 435 antibodies from 37 providers.
DR DNASU; 7337; -.
DR Ensembl; ENST00000428984.6; ENSP00000401265.2; ENSG00000114062.22. [Q05086-2]
DR Ensembl; ENST00000438097.6; ENSP00000411258.1; ENSG00000114062.22. [Q05086-2]
DR Ensembl; ENST00000566215.5; ENSP00000457771.1; ENSG00000114062.22. [Q05086-2]
DR Ensembl; ENST00000630424.2; ENSP00000486349.1; ENSG00000114062.22. [Q05086-2]
DR Ensembl; ENST00000637886.1; ENSP00000490258.1; ENSG00000114062.22. [Q05086-3]
DR Ensembl; ENST00000638011.1; ENSP00000490111.1; ENSG00000114062.22. [Q05086-2]
DR Ensembl; ENST00000638155.1; ENSP00000490557.1; ENSG00000114062.22. [Q05086-2]
DR Ensembl; ENST00000648336.2; ENSP00000497572.2; ENSG00000114062.22. [Q05086-3]
DR Ensembl; ENST00000649550.1; ENSP00000497549.1; ENSG00000114062.22. [Q05086-2]
DR Ensembl; ENST00000650110.1; ENSP00000497594.1; ENSG00000114062.22. [Q05086-1]
DR GeneID; 7337; -.
DR KEGG; hsa:7337; -.
DR MANE-Select; ENST00000648336.2; ENSP00000497572.2; NM_130839.5; NP_570854.1. [Q05086-3]
DR UCSC; uc001zaq.4; human. [Q05086-1]
DR CTD; 7337; -.
DR DisGeNET; 7337; -.
DR GeneCards; UBE3A; -.
DR GeneReviews; UBE3A; -.
DR HGNC; HGNC:12496; UBE3A.
DR HPA; ENSG00000114062; Low tissue specificity.
DR MalaCards; UBE3A; -.
DR MIM; 105830; phenotype.
DR MIM; 601623; gene.
DR neXtProt; NX_Q05086; -.
DR OpenTargets; ENSG00000114062; -.
DR Orphanet; 238446; 15q11q13 microduplication syndrome.
DR Orphanet; 411511; Angelman syndrome due to a point mutation.
DR Orphanet; 411515; Angelman syndrome due to imprinting defect in 15q11-q13.
DR Orphanet; 98794; Angelman syndrome due to maternal 15q11q13 deletion.
DR Orphanet; 98795; Angelman syndrome due to paternal uniparental disomy of chromosome 15.
DR PharmGKB; PA37144; -.
DR VEuPathDB; HostDB:ENSG00000114062; -.
DR eggNOG; KOG0941; Eukaryota.
DR GeneTree; ENSGT00940000155050; -.
DR InParanoid; Q05086; -.
DR OMA; GNAHCTN; -.
DR OrthoDB; 339404at2759; -.
DR PhylomeDB; Q05086; -.
DR TreeFam; TF315189; -.
DR BRENDA; 2.3.2.26; 2681.
DR PathwayCommons; Q05086; -.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q05086; -.
DR SIGNOR; Q05086; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 7337; 17 hits in 1123 CRISPR screens.
DR ChiTaRS; UBE3A; human.
DR EvolutionaryTrace; Q05086; -.
DR GeneWiki; UBE3A; -.
DR GenomeRNAi; 7337; -.
DR Pharos; Q05086; Tbio.
DR PRO; PR:Q05086; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q05086; protein.
DR Bgee; ENSG00000114062; Expressed in sperm and 214 other tissues.
DR ExpressionAtlas; Q05086; baseline and differential.
DR Genevisible; Q05086; HS.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0000502; C:proteasome complex; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003713; F:transcription coactivator activity; IEA:Ensembl.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IMP:CACAO.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB.
DR GO; GO:0030521; P:androgen receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0007420; P:brain development; TAS:ProtInc.
DR GO; GO:1990416; P:cellular response to brain-derived neurotrophic factor stimulus; IEA:Ensembl.
DR GO; GO:0035641; P:locomotory exploration behavior; IEA:Ensembl.
DR GO; GO:0061743; P:motor learning; IEA:Ensembl.
DR GO; GO:0061002; P:negative regulation of dendritic spine morphogenesis; IEA:Ensembl.
DR GO; GO:0001541; P:ovarian follicle development; IEA:Ensembl.
DR GO; GO:1905528; P:positive regulation of Golgi lumen acidification; IEA:Ensembl.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IEA:Ensembl.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IDA:CACAO.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0050847; P:progesterone receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0060736; P:prostate gland growth; IEA:Ensembl.
DR GO; GO:0051865; P:protein autoubiquitination; IDA:FlyBase.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; IBA:GO_Central.
DR GO; GO:0006508; P:proteolysis; TAS:ProtInc.
DR GO; GO:0042752; P:regulation of circadian rhythm; IMP:UniProtKB.
DR GO; GO:2000058; P:regulation of ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:0042220; P:response to cocaine; IEA:Ensembl.
DR GO; GO:0042542; P:response to hydrogen peroxide; IEA:Ensembl.
DR GO; GO:0032570; P:response to progesterone; IDA:UniProtKB.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR GO; GO:0035037; P:sperm entry; IEA:Ensembl.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; TAS:ProtInc.
DR CDD; cd00078; HECTc; 1.
DR Gene3D; 6.10.130.10; -; 1.
DR IDEAL; IID00209; -.
DR InterPro; IPR032353; AZUL.
DR InterPro; IPR042556; AZUL_sf.
DR InterPro; IPR000569; HECT_dom.
DR InterPro; IPR035983; Hect_E3_ubiquitin_ligase.
DR InterPro; IPR017134; UBE3A.
DR Pfam; PF16558; AZUL; 1.
DR Pfam; PF00632; HECT; 1.
DR PIRSF; PIRSF037201; Ubiquitin-protein_ligase_E6-AP; 1.
DR SMART; SM00119; HECTc; 1.
DR SUPFAM; SSF56204; SSF56204; 1.
DR PROSITE; PS50237; HECT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Biological rhythms; Cytoplasm;
KW Direct protein sequencing; Disease variant; Host-virus interaction;
KW Metal-binding; Nucleus; Phosphoprotein; Proteasome; Reference proteome;
KW Transferase; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..875
FT /note="Ubiquitin-protein ligase E3A"
FT /id="PRO_0000194980"
FT DOMAIN 776..875
FT /note="HECT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT ZN_FING 44..83
FT /note="C4-type; atypical"
FT /evidence="ECO:0000269|PubMed:21947926"
FT REGION 175..226
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 401..418
FT /note="E6-binding"
FT REGION 418..517
FT /note="Interaction with HCV core protein"
FT COMPBIAS 175..201
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 212..226
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 843
FT /note="Glycyl thioester intermediate"
FT MOD_RES 218
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17525332,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 659
FT /note="Phosphotyrosine; by ABL1"
FT /evidence="ECO:0000269|PubMed:23581475"
FT VAR_SEQ 1..23
FT /note="Missing (in isoform I)"
FT /evidence="ECO:0000303|PubMed:8988171,
FT ECO:0000303|PubMed:9143503"
FT /id="VSP_006705"
FT VAR_SEQ 1..10
FT /note="MEKLHQCYWK -> MATACKR (in isoform III)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:9143503"
FT /id="VSP_006706"
FT VARIANT 44
FT /note="C -> Y"
FT /evidence="ECO:0000269|PubMed:8988172"
FT /id="VAR_007852"
FT VARIANT 62
FT /note="R -> H (in dbSNP:rs587784511)"
FT /evidence="ECO:0000269|PubMed:9585605"
FT /id="VAR_008142"
FT VARIANT 129
FT /note="T -> K (in AS; unknown pathological significance;
FT dbSNP:rs587781241)"
FT /evidence="ECO:0000269|PubMed:25212744"
FT /id="VAR_073196"
FT VARIANT 140
FT /note="C -> R (may be associated with AS;
FT dbSNP:rs587782907)"
FT /evidence="ECO:0000269|PubMed:25212744"
FT /id="VAR_073197"
FT VARIANT 156
FT /note="V -> G (may be associated with AS;
FT dbSNP:rs587782915)"
FT /evidence="ECO:0000269|PubMed:25212744"
FT /id="VAR_073198"
FT VARIANT 201
FT /note="A -> T (in dbSNP:rs147145506)"
FT /evidence="ECO:0000269|PubMed:8988172,
FT ECO:0000269|PubMed:9585605"
FT /id="VAR_007853"
FT VARIANT 235
FT /note="D -> V (in AS; unknown pathological significance;
FT dbSNP:rs587780581)"
FT /evidence="ECO:0000269|PubMed:25212744"
FT /id="VAR_073199"
FT VARIANT 260
FT /note="L -> H (in AS; unknown pathological significance;
FT dbSNP:rs587780582)"
FT /evidence="ECO:0000269|PubMed:25212744"
FT /id="VAR_073200"
FT VARIANT 260
FT /note="L -> Q (in AS; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:25212744"
FT /id="VAR_073201"
FT VARIANT 286
FT /note="L -> W (in AS; unknown pathological significance;
FT dbSNP:rs587780583)"
FT /evidence="ECO:0000269|PubMed:25212744"
FT /id="VAR_073202"
FT VARIANT 290
FT /note="V -> G (in dbSNP:rs1059383)"
FT /evidence="ECO:0000269|PubMed:8380895,
FT ECO:0000269|PubMed:9143503, ECO:0000269|Ref.9"
FT /id="VAR_047516"
FT VARIANT 293
FT /note="N -> T (may be associated with AS;
FT dbSNP:rs587782908)"
FT /evidence="ECO:0000269|PubMed:25212744"
FT /id="VAR_073203"
FT VARIANT 358
FT /note="S -> T (may be associated with AS;
FT dbSNP:rs141984760)"
FT /evidence="ECO:0000269|PubMed:25212744"
FT /id="VAR_073204"
FT VARIANT 372
FT /note="S -> P"
FT /evidence="ECO:0000269|PubMed:9585605"
FT /id="VAR_008143"
FT VARIANT 458
FT /note="L -> P (in AS; unknown pathological significance;
FT dbSNP:rs587781242)"
FT /evidence="ECO:0000269|PubMed:25212744"
FT /id="VAR_073205"
FT VARIANT 481
FT /note="P -> L (in AS; unknown pathological significance;
FT dbSNP:rs587780584)"
FT /evidence="ECO:0000269|PubMed:25212744"
FT /id="VAR_073206"
FT VARIANT 500
FT /note="R -> P (in AS; unknown pathological significance;
FT dbSNP:rs587781243)"
FT /evidence="ECO:0000269|PubMed:25212744"
FT /id="VAR_073207"
FT VARIANT 501
FT /note="M -> I (may be associated with AS;
FT dbSNP:rs587782916)"
FT /evidence="ECO:0000269|PubMed:25212744"
FT /id="VAR_073208"
FT VARIANT 568
FT /note="G -> R (in AS; unknown pathological significance;
FT dbSNP:rs587781233)"
FT /evidence="ECO:0000269|PubMed:25212744"
FT /id="VAR_073209"
FT VARIANT 589
FT /note="M -> K (in AS; unknown pathological significance;
FT dbSNP:rs587781244)"
FT /evidence="ECO:0000269|PubMed:25212744"
FT /id="VAR_073210"
FT VARIANT 607
FT /note="E -> Q (in AS; unknown pathological significance;
FT dbSNP:rs587781235)"
FT /evidence="ECO:0000269|PubMed:25212744"
FT /id="VAR_073211"
FT VARIANT 611
FT /note="Q -> E (may be associated with AS;
FT dbSNP:rs587782918)"
FT /evidence="ECO:0000269|PubMed:25212744"
FT /id="VAR_073212"
FT VARIANT 611
FT /note="Q -> P (may be associated with AS;
FT dbSNP:rs587782919)"
FT /evidence="ECO:0000269|PubMed:25212744"
FT /id="VAR_073213"
FT VARIANT 679
FT /note="T -> I (in AS; unknown pathological significance;
FT dbSNP:rs587781236)"
FT /evidence="ECO:0000269|PubMed:25212744"
FT /id="VAR_073214"
FT VARIANT 696
FT /note="L -> R (may be associated with AS;
FT dbSNP:rs587782920)"
FT /evidence="ECO:0000269|PubMed:25212744"
FT /id="VAR_073215"
FT VARIANT 713
FT /note="F -> C (in AS; unknown pathological significance;
FT dbSNP:rs587781237)"
FT /evidence="ECO:0000269|PubMed:25212744"
FT /id="VAR_073216"
FT VARIANT 785
FT /note="V -> I (may be associated with AS;
FT dbSNP:rs587782910)"
FT /evidence="ECO:0000269|PubMed:25212744"
FT /id="VAR_073217"
FT VARIANT 826
FT /note="I -> II (in AS)"
FT /evidence="ECO:0000269|PubMed:9585605"
FT /id="VAR_008144"
FT VARIANT 850
FT /note="P -> L (in AS; unknown pathological significance;
FT dbSNP:rs587781239)"
FT /evidence="ECO:0000269|PubMed:25212744"
FT /id="VAR_073218"
FT MUTAGEN 750
FT /note="F->D: Disrupt trimer formation, 50-fold reduction in
FT E3 ligase activity."
FT /evidence="ECO:0000269|PubMed:24273172"
FT CONFLICT 359
FT /note="R -> RNLVNEFNSR (in Ref. 7; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 423
FT /note="P -> L (in Ref. 7; AAA35542)"
FT /evidence="ECO:0000305"
FT CONFLICT 647..649
FT /note="TFR -> LFV (in Ref. 7; AAA35542)"
FT /evidence="ECO:0000305"
FT CONFLICT 669
FT /note="E -> V (in Ref. 7; AAA35542)"
FT /evidence="ECO:0000305"
FT CONFLICT 686
FT /note="D -> N (in Ref. 7; AAA35542)"
FT /evidence="ECO:0000305"
FT HELIX 27..41
FT /evidence="ECO:0007829|PDB:2KR1"
FT HELIX 65..78
FT /evidence="ECO:0007829|PDB:2KR1"
FT HELIX 405..412
FT /evidence="ECO:0007829|PDB:6SJV"
FT STRAND 525..527
FT /evidence="ECO:0007829|PDB:1C4Z"
FT STRAND 529..531
FT /evidence="ECO:0007829|PDB:1C4Z"
FT HELIX 532..545
FT /evidence="ECO:0007829|PDB:1C4Z"
FT HELIX 548..552
FT /evidence="ECO:0007829|PDB:1C4Z"
FT STRAND 557..559
FT /evidence="ECO:0007829|PDB:1C4Z"
FT HELIX 569..582
FT /evidence="ECO:0007829|PDB:1C4Z"
FT HELIX 585..587
FT /evidence="ECO:0007829|PDB:1C4Z"
FT STRAND 589..592
FT /evidence="ECO:0007829|PDB:1C4Z"
FT TURN 594..596
FT /evidence="ECO:0007829|PDB:1C4Z"
FT STRAND 599..601
FT /evidence="ECO:0007829|PDB:1C4Z"
FT HELIX 609..624
FT /evidence="ECO:0007829|PDB:1C4Z"
FT HELIX 635..641
FT /evidence="ECO:0007829|PDB:1C4Z"
FT HELIX 648..654
FT /evidence="ECO:0007829|PDB:1C4Z"
FT HELIX 656..667
FT /evidence="ECO:0007829|PDB:1C4Z"
FT HELIX 672..675
FT /evidence="ECO:0007829|PDB:1C4Z"
FT STRAND 679..684
FT /evidence="ECO:0007829|PDB:1C4Z"
FT TURN 687..689
FT /evidence="ECO:0007829|PDB:1C4Z"
FT STRAND 692..697
FT /evidence="ECO:0007829|PDB:1C4Z"
FT TURN 698..702
FT /evidence="ECO:0007829|PDB:1C4Z"
FT TURN 707..709
FT /evidence="ECO:0007829|PDB:1C4Z"
FT HELIX 710..722
FT /evidence="ECO:0007829|PDB:1C4Z"
FT HELIX 727..741
FT /evidence="ECO:0007829|PDB:1C4Z"
FT STRAND 742..744
FT /evidence="ECO:0007829|PDB:1C4Z"
FT HELIX 753..760
FT /evidence="ECO:0007829|PDB:1C4Z"
FT HELIX 767..773
FT /evidence="ECO:0007829|PDB:6TGK"
FT STRAND 775..777
FT /evidence="ECO:0007829|PDB:6TGK"
FT HELIX 785..795
FT /evidence="ECO:0007829|PDB:6TGK"
FT HELIX 799..810
FT /evidence="ECO:0007829|PDB:6TGK"
FT STRAND 811..814
FT /evidence="ECO:0007829|PDB:6TGK"
FT HELIX 820..822
FT /evidence="ECO:0007829|PDB:6TGK"
FT STRAND 826..828
FT /evidence="ECO:0007829|PDB:6TGK"
FT STRAND 839..841
FT /evidence="ECO:0007829|PDB:1C4Z"
FT HELIX 842..844
FT /evidence="ECO:0007829|PDB:1C4Z"
FT STRAND 846..851
FT /evidence="ECO:0007829|PDB:1C4Z"
FT HELIX 855..867
FT /evidence="ECO:0007829|PDB:6TGK"
SQ SEQUENCE 875 AA; 100688 MW; F80F0502B3B3838A CRC64;
MEKLHQCYWK SGEPQSDDIE ASRMKRAAAK HLIERYYHQL TEGCGNEACT NEFCASCPTF
LRMDNNAAAI KALELYKINA KLCDPHPSKK GASSAYLENS KGAPNNSCSE IKMNKKGARI
DFKDVTYLTE EKVYEILELC REREDYSPLI RVIGRVFSSA EALVQSFRKV KQHTKEELKS
LQAKDEDKDE DEKEKAACSA AAMEEDSEAS SSRIGDSSQG DNNLQKLGPD DVSVDIDAIR
RVYTRLLSNE KIETAFLNAL VYLSPNVECD LTYHNVYSRD PNYLNLFIIV MENRNLHSPE
YLEMALPLFC KAMSKLPLAA QGKLIRLWSK YNADQIRRMM ETFQQLITYK VISNEFNSRN
LVNDDDAIVA ASKCLKMVYY ANVVGGEVDT NHNEEDDEEP IPESSELTLQ ELLGEERRNK
KGPRVDPLET ELGVKTLDCR KPLIPFEEFI NEPLNEVLEM DKDYTFFKVE TENKFSFMTC
PFILNAVTKN LGLYYDNRIR MYSERRITVL YSLVQGQQLN PYLRLKVRRD HIIDDALVRL
EMIAMENPAD LKKQLYVEFE GEQGVDEGGV SKEFFQLVVE EIFNPDIGMF TYDESTKLFW
FNPSSFETEG QFTLIGIVLG LAIYNNCILD VHFPMVVYRK LMGKKGTFRD LGDSHPVLYQ
SLKDLLEYEG NVEDDMMITF QISQTDLFGN PMMYDLKENG DKIPITNENR KEFVNLYSDY
ILNKSVEKQF KAFRRGFHMV TNESPLKYLF RPEEIELLIC GSRNLDFQAL EETTEYDGGY
TRDSVLIREF WEIVHSFTDE QKRLFLQFTT GTDRAPVGGL GKLKMIIAKN GPDTERLPTS
HTCFNVLLLP EYSSKEKLKE RLLKAITYAK GFGML
