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 27-MAR-2024, entry version 227. 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}, EPVE6AP GN {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 BMAL1. 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 FUNCTION. RX PubMed=30020076; DOI=10.7554/elife.37993; RA Sun J., Liu Y., Jia Y., Hao X., Lin W.J., Tran J., Lynch G., Baudry M., RA Bi X.; RT "UBE3A-mediated p18/LAMTOR1 ubiquitination and degradation regulate mTORC1 RT activity and synaptic plasticity."; RL Elife 7:0-0(2018). RN [30] 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 [31] 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 [32] 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 [33] 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 [34] 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, PubMed:30020076). CC Several substrates have been identified including the BMAL1, ARC, CC LAMTOR1, RAD23A and RAD23B, MCM7 (which is involved in DNA CC replication), annexin A1, the PML tumor suppressor, and the cell cycle CC regulator CDKN1B (PubMed:10373495, PubMed:19204938, PubMed:19325566, CC PubMed:19591933, PubMed:22645313, PubMed:24728990, PubMed:30020076). CC Additionally, may function as a cellular quality control ubiquitin CC ligase by helping the degradation of the cytoplasmic misfolded proteins CC (PubMed:19233847). Finally, UBE3A also promotes its own degradation in CC vivo. Plays an important role in the regulation of the circadian clock: CC involved in the ubiquitination of the core clock component BMAL1, CC leading to its proteasomal degradation (PubMed:24728990). Acts as CC transcriptional coactivator of progesterone receptor PGR upon CC progesterone hormone activation (PubMed:16772533). Acts as a regulator CC of synaptic development by mediating ubiquitination and degradation of CC ARC (By similarity). Required for synaptic remodeling in neurons by CC mediating ubiquitination and degradation of LAMTOR1, thereby limiting CC mTORC1 signaling and activity-dependent synaptic remodeling (By CC similarity). Synergizes with WBP2 in enhancing PGR activity CC (PubMed:16772533). {ECO:0000250|UniProtKB:O08759, CC ECO:0000269|PubMed:10373495, ECO:0000269|PubMed:16772533, CC ECO:0000269|PubMed:19204938, ECO:0000269|PubMed:19233847, CC ECO:0000269|PubMed:19325566, ECO:0000269|PubMed:19591933, CC ECO:0000269|PubMed:22645313, ECO:0000269|PubMed:24273172, CC ECO:0000269|PubMed:24728990, ECO:0000269|PubMed:30020076}. 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 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="https://atlasgeneticsoncology.org/gene/42756/UBE3A"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 PDB; 7Q41; X-ray; 3.01 A; B/D/F=183-197. DR PDB; 7QPB; X-ray; 2.34 A; A/B/C/D=764-875. DR PDB; 8ENP; NMR; -; A=10-87. DR PDB; 8EPT; NMR; -; A=1-87. DR PDB; 8R1F; EM; 3.67 A; A=1-875. DR PDB; 8R1G; EM; 3.99 A; A/D=1-875. 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 PDBsum; 7Q41; -. DR PDBsum; 7QPB; -. DR PDBsum; 8ENP; -. DR PDBsum; 8EPT; -. DR PDBsum; 8R1F; -. DR PDBsum; 8R1G; -. DR AlphaFoldDB; Q05086; -. DR BMRB; Q05086; -. DR SMR; Q05086; -. DR BioGRID; 113185; 423. DR CORUM; Q05086; -. DR DIP; DIP-6002N; -. DR IntAct; Q05086; 160. DR MINT; Q05086; -. DR STRING; 9606.ENSP00000497594; -. DR MoonDB; Q05086; Predicted. DR GlyCosmos; Q05086; 1 site, 2 glycans. DR GlyGen; Q05086; 2 sites, 2 O-linked glycans (2 sites). 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; 9606-ENSP00000232165; -. DR PeptideAtlas; Q05086; -. DR ProteomicsDB; 58306; -. [Q05086-1] DR ProteomicsDB; 58307; -. [Q05086-2] DR ProteomicsDB; 58308; -. [Q05086-3] DR Pumba; Q05086; -. DR Antibodypedia; 9118; 487 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 AGR; HGNC:12496; -. 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; AHCTNAN; -. DR OrthoDB; 5471864at2759; -. 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; 20 hits in 1199 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 216 other cell types or tissues. DR ExpressionAtlas; Q05086; baseline and differential. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl. 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; IDA:UniProtKB. 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:1904262; P:negative regulation of TORC1 signaling; ISS:UniProtKB. 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:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; 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:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISS:UniProtKB. 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:0048167; P:regulation of synaptic plasticity; ISS: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; 3.30.2160.10; Hect, E3 ligase catalytic domain; 1. DR Gene3D; 3.30.2410.10; Hect, E3 ligase catalytic domain; 1. DR Gene3D; 3.90.1750.10; Hect, E3 ligase catalytic domains; 1. DR Gene3D; 6.10.130.10; Ubiquitin-protein ligase E3A, N-terminal zinc-binding domain (AZUL); 1. DR IDEAL; IID00209; -. DR InterPro; IPR032353; AZUL. DR InterPro; IPR042556; AZUL_sf. DR InterPro; IPR044611; E3A/B/C-like. DR InterPro; IPR000569; HECT_dom. DR InterPro; IPR035983; Hect_E3_ubiquitin_ligase. DR InterPro; IPR017134; UBE3A. DR PANTHER; PTHR45700; UBIQUITIN-PROTEIN LIGASE E3C; 1. DR PANTHER; PTHR45700:SF2; UBIQUITIN-PROTEIN LIGASE E3C; 1. 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; Hect, E3 ligase catalytic domain; 1. DR PROSITE; PS50237; HECT; 1. DR Genevisible; Q05086; HS. 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; uncertain 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; uncertain significance; FT dbSNP:rs587780581)" FT /evidence="ECO:0000269|PubMed:25212744" FT /id="VAR_073199" FT VARIANT 260 FT /note="L -> H (in AS; uncertain significance; FT dbSNP:rs587780582)" FT /evidence="ECO:0000269|PubMed:25212744" FT /id="VAR_073200" FT VARIANT 260 FT /note="L -> Q (in AS; uncertain significance)" FT /evidence="ECO:0000269|PubMed:25212744" FT /id="VAR_073201" FT VARIANT 286 FT /note="L -> W (in AS; uncertain 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; uncertain significance; FT dbSNP:rs587781242)" FT /evidence="ECO:0000269|PubMed:25212744" FT /id="VAR_073205" FT VARIANT 481 FT /note="P -> L (in AS; uncertain significance; FT dbSNP:rs587780584)" FT /evidence="ECO:0000269|PubMed:25212744" FT /id="VAR_073206" FT VARIANT 500 FT /note="R -> P (in AS; uncertain 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; uncertain significance; FT dbSNP:rs587781233)" FT /evidence="ECO:0000269|PubMed:25212744" FT /id="VAR_073209" FT VARIANT 589 FT /note="M -> K (in AS; uncertain significance; FT dbSNP:rs587781244)" FT /evidence="ECO:0000269|PubMed:25212744" FT /id="VAR_073210" FT VARIANT 607 FT /note="E -> Q (in AS; uncertain 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; uncertain 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; uncertain 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; uncertain 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 831..833 FT /evidence="ECO:0007829|PDB:7QPB" FT STRAND 839..841 FT /evidence="ECO:0007829|PDB:7QPB" FT TURN 842..845 FT /evidence="ECO:0007829|PDB:7QPB" FT STRAND 846..849 FT /evidence="ECO:0007829|PDB:7QPB" 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 //