SQSTM_HUMAN
ID SQSTM_HUMAN Reviewed; 440 AA.
AC Q13501; A6NFN7; B2R661; B3KUW5; Q13446; Q9BUV7; Q9BVS6; Q9UEU1;
DT 11-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 220.
DE RecName: Full=Sequestosome-1;
DE AltName: Full=EBI3-associated protein of 60 kDa;
DE Short=EBIAP;
DE Short=p60;
DE AltName: Full=Phosphotyrosine-independent ligand for the Lck SH2 domain of 62 kDa;
DE AltName: Full=Ubiquitin-binding protein p62;
GN Name=SQSTM1; Synonyms=ORCA, OSIL;
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), PROTEIN SEQUENCE OF 345-361 AND
RP 394-411, AND INTERACTION WITH EBI3.
RC TISSUE=B-cell;
RX PubMed=8551575; DOI=10.1128/jvi.70.2.1143-1153.1996;
RA Devergne O., Hummel M., Koeppen H., Le Beau M.M., Nathanson E.C., Kieff E.,
RA Birkenbach M.;
RT "A novel interleukin-12 p40-related protein induced by latent Epstein-Barr
RT virus infection in B lymphocytes.";
RL J. Virol. 70:1143-1153(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 51-96; 184-187;
RP 213-217; 239-264 AND 268-281, TISSUE SPECIFICITY, INTERACTION WITH LCK, AND
RP MUTAGENESIS OF TYR-9.
RC TISSUE=Cervix carcinoma;
RX PubMed=8650207; DOI=10.1073/pnas.93.12.5991;
RA Joung I., Strominger J.L., Shin J.;
RT "Molecular cloning of a phosphotyrosine-independent ligand of the p56lck
RT SH2 domain.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:5991-5995(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Caudate nucleus, and Trachea;
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=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Pancreas, Placenta, Skin, and Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-72, AND INDUCTION.
RX PubMed=9762895; DOI=10.1016/s0014-5793(98)01021-7;
RA Vadlamudi R.K., Shin J.;
RT "Genomic structure and promoter analysis of the p62 gene encoding a non-
RT proteasomal multiubiquitin chain binding protein.";
RL FEBS Lett. 435:138-142(1998).
RN [7]
RP PROTEIN SEQUENCE OF 51-60; 166-174 AND 379-388, AND SUBCELLULAR LOCATION.
RX PubMed=10362795; DOI=10.1016/s0002-9440(10)65426-0;
RA Stumptner C., Heid H., Fuchsbichler A., Hauser H., Mischinger H.-J.,
RA Zatloukal K., Denk H.;
RT "Analysis of intracytoplasmic hyaline bodies in a hepatocellular carcinoma.
RT Demonstration of p62 as major constituent.";
RL Am. J. Pathol. 154:1701-1710(1999).
RN [8]
RP INTERACTION WITH LCK AND RASA1.
RX PubMed=8618896; DOI=10.1073/pnas.92.26.12338;
RA Park I., Chung J., Walsh C.T., Yun Y., Strominger J.L., Shin J.;
RT "Phosphotyrosine-independent binding of a 62-kDa protein to the src
RT homology 2 (SH2) domain of p56lck and its regulation by phosphorylation of
RT Ser-59 in the lck unique N-terminal region.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:12338-12342(1995).
RN [9]
RP INTERACTION WITH UBIQUITIN.
RX PubMed=8702753; DOI=10.1074/jbc.271.34.20235;
RA Vadlamudi R.K., Joung I., Strominger J.L., Shin J.;
RT "p62, a phosphotyrosine-independent ligand of the SH2 domain of p56lck,
RT belongs to a new class of ubiquitin-binding proteins.";
RL J. Biol. Chem. 271:20235-20237(1996).
RN [10]
RP INTERACTION WITH NR2F2.
RX PubMed=8910285; DOI=10.1074/jbc.271.44.27197;
RA Marcus S.L., Winrow C.J., Capone J.P., Rachubinski R.A.;
RT "A p56(lck) ligand serves as a coactivator of an orphan nuclear hormone
RT receptor.";
RL J. Biol. Chem. 271:27197-27200(1996).
RN [11]
RP INTERACTION WITH PRKCI AND PRKCZ, AND SUBCELLULAR LOCATION.
RX PubMed=9566925; DOI=10.1128/mcb.18.5.3069;
RA Sanchez P., De Carcer G., Sandoval I.V., Moscat J., Diaz-Meco M.T.;
RT "Localization of atypical protein kinase C isoforms into lysosome-targeted
RT endosomes through interaction with p62.";
RL Mol. Cell. Biol. 18:3069-3080(1998).
RN [12]
RP INTERACTION WITH RIPK1; PRKCZ; PRKCI; IKBKB; TRADD AND TNFRSF1A, AND
RP FUNCTION.
RX PubMed=10356400; DOI=10.1093/emboj/18.11.3044;
RA Sanz L., Sanchez P., Lallena M.-J., Diaz-Meco M.T., Moscat J.;
RT "The interaction of p62 with RIP links the atypical PKCs to NF-kappaB
RT activation.";
RL EMBO J. 18:3044-3053(1999).
RN [13]
RP INTERACTION WITH MAPKAPK5, AND SUBCELLULAR LOCATION.
RX PubMed=10708586; DOI=10.1006/bbrc.2000.2333;
RA Sudo T., Maruyama M., Osada H.;
RT "p62 functions as a p38 MAP kinase regulator.";
RL Biochem. Biophys. Res. Commun. 269:521-525(2000).
RN [14]
RP INTERACTION WITH TRAF6 AND RIPK1, DOMAIN, AND FUNCTION.
RX PubMed=10747026; DOI=10.1093/emboj/19.7.1576;
RA Sanz L., Diaz-Meco M.T., Nakano H., Moscat J.;
RT "The atypical PKC-interacting protein p62 channels NF-kappaB activation by
RT the IL-1-TRAF6 pathway.";
RL EMBO J. 19:1576-1586(2000).
RN [15]
RP INTERACTION WITH NTRK1; TRAF6; NGFR AND PRKCZ, AND FUNCTION.
RX PubMed=11244088; DOI=10.1074/jbc.c000869200;
RA Wooten M.W., Seibenhener M.L., Mamidipudi V., Diaz-Meco M.T., Barker P.A.,
RA Moscat J.;
RT "The atypical protein kinase C-interacting protein p62 is a scaffold for
RT NF-kappaB activation by nerve growth factor.";
RL J. Biol. Chem. 276:7709-7712(2001).
RN [16]
RP SUBCELLULAR LOCATION, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=11786419; DOI=10.1016/s0002-9440(10)64369-6;
RA Zatloukal K., Stumptner C., Fuchsbichler A., Heid H., Schnoelzer M.,
RA Kenner L., Kleinert R., Prinz M., Aguzzi A., Denk H.;
RT "p62 Is a common component of cytoplasmic inclusions in protein aggregation
RT diseases.";
RL Am. J. Pathol. 160:255-263(2002).
RN [17]
RP INTERACTION WITH PAWR AND PRKCZ.
RX PubMed=11755531; DOI=10.1016/s0014-5793(01)03224-0;
RA Chang S., Kim J.H., Shin J.;
RT "p62 forms a ternary complex with PKCzeta and PAR-4 and antagonizes PAR-4-
RT induced PKCzeta inhibition.";
RL FEBS Lett. 510:57-61(2002).
RN [18]
RP SUBCELLULAR LOCATION.
RX PubMed=11981755; DOI=10.1053/jhep.2002.32674;
RA Stumptner C., Fuchsbichler A., Heid H., Zatloukal K., Denk H.;
RT "Mallory body -- a disease-associated type of sequestosome.";
RL Hepatology 35:1053-1062(2002).
RN [19]
RP INTERACTION WITH NTRK1; NTRK2 AND NTRK3, SUBCELLULAR LOCATION, AND
RP FUNCTION.
RX PubMed=12471037; DOI=10.1074/jbc.m208468200;
RA Geetha T., Wooten M.W.;
RT "Association of the atypical protein kinase C-interacting protein p62/ZIP
RT with nerve growth factor receptor TrkA regulates receptor trafficking and
RT Erk5 signaling.";
RL J. Biol. Chem. 278:4730-4739(2003).
RN [20]
RP INTERACTION WITH PRKCI; PRKCZ; MAP2K5 AND NBR1, DOMAIN, MUTAGENESIS OF
RP LYS-7; LYS-13; 21-ARG-ARG-22; TYR-67; ASP-69; ASP-71; ASP-73; ASP-80 AND
RP GLU-82, AND DIMERIZATION.
RX PubMed=12813044; DOI=10.1074/jbc.m303221200;
RA Lamark T., Perander M., Outzen H., Kristiansen K., Oevervatn A.,
RA Michaelsen E., Bjoerkoey G., Johansen T.;
RT "Interaction codes within the family of mammalian Phox and Bem1p domain-
RT containing proteins.";
RL J. Biol. Chem. 278:34568-34581(2003).
RN [21]
RP INTERACTION WITH PRKCZ, DOMAIN, OLIGOMERIZATION, AND MUTAGENESIS OF LYS-7;
RP ASP-69 AND ASP-73.
RX PubMed=12887891; DOI=10.1016/s1097-2765(03)00246-6;
RA Wilson M.I., Gill D.J., Perisic O., Quinn M.T., Williams R.L.;
RT "PB1 domain-mediated heterodimerization in NADPH oxidase and signaling
RT complexes of atypical protein kinase C with Par6 and p62.";
RL Mol. Cell 12:39-50(2003).
RN [22]
RP INDUCTION.
RX PubMed=12700667; DOI=10.1038/sj.onc.1206325;
RA Thompson H.G.R., Harris J.W., Wold B.J., Lin F., Brody J.P.;
RT "p62 overexpression in breast tumors and regulation by prostate-derived Ets
RT factor in breast cancer cells.";
RL Oncogene 22:2322-2333(2003).
RN [23]
RP SUBCELLULAR LOCATION.
RX PubMed=15158159; DOI=10.1016/j.brainres.2004.03.029;
RA Nakaso K., Yoshimoto Y., Nakano T., Takeshima T., Fukuhara Y., Yasui K.,
RA Araga S., Yanagawa T., Ishii T., Nakashima K.;
RT "Transcriptional activation of p62/A170/ZIP during the formation of the
RT aggregates: possible mechanisms and the role in Lewy body formation in
RT Parkinson's disease.";
RL Brain Res. 1012:42-51(2004).
RN [24]
RP INTERACTION WITH TRAF6; PSMC2 AND PSMD4, DOMAIN, MUTAGENESIS OF LEU-398;
RP PHE-406; LEU-413; LEU-417 AND ILE-431, AND FUNCTION.
RX PubMed=15340068; DOI=10.1128/mcb.24.18.8055-8068.2004;
RA Seibenhener M.L., Babu J.R., Geetha T., Wong H.C., Krishna N.R.,
RA Wooten M.W.;
RT "Sequestosome 1/p62 is a polyubiquitin chain binding protein involved in
RT ubiquitin proteasome degradation.";
RL Mol. Cell. Biol. 24:8055-8068(2004).
RN [25]
RP FUNCTION.
RX PubMed=16079148; DOI=10.1074/jbc.c500237200;
RA Wooten M.W., Geetha T., Seibenhener M.L., Babu J.R., Diaz-Meco M.T.,
RA Moscat J.;
RT "The p62 scaffold regulates nerve growth factor-induced NF-kappaB
RT activation by influencing TRAF6 polyubiquitination.";
RL J. Biol. Chem. 280:35625-35629(2005).
RN [26]
RP FUNCTION, SUBCELLULAR LOCATION, HOMOOLIGOMERIZATION, INTERACTION WITH
RP MAP1LC3B, POSSIBLE PROTECTIVE ROLE IN HD, AND MUTAGENESIS OF ASP-69 AND
RP ILE-431.
RX PubMed=16286508; DOI=10.1083/jcb.200507002;
RA Bjorkoy G., Lamark T., Brech A., Outzen H., Perander M., Overvatn A.,
RA Stenmark H., Johansen T.;
RT "p62/SQSTM1 forms protein aggregates degraded by autophagy and has a
RT protective effect on huntingtin-induced cell death.";
RL J. Cell Biol. 171:603-614(2005).
RN [27]
RP INTERACTION WITH MAPT, DOMAIN, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=15953362; DOI=10.1111/j.1471-4159.2005.03181.x;
RA Babu J.R., Geetha T., Wooten M.W.;
RT "Sequestosome 1/p62 shuttles polyubiquitinated tau for proteasomal
RT degradation.";
RL J. Neurochem. 94:192-203(2005).
RN [28]
RP INTERACTION WITH AJUBA AND LIMD1.
RX PubMed=15870274; DOI=10.1128/mcb.25.10.4010-4022.2005;
RA Feng Y., Longmore G.D.;
RT "The LIM protein Ajuba influences interleukin-1-induced NF-kappaB
RT activation by affecting the assembly and activity of the protein kinase
RT Czeta/p62/TRAF6 signaling complex.";
RL Mol. Cell. Biol. 25:4010-4022(2005).
RN [29]
RP INDUCTION, AND FUNCTION.
RX PubMed=15911346; DOI=10.1016/j.mcn.2005.02.011;
RA Wang Z., Figueiredo-Pereira M.E.;
RT "Inhibition of sequestosome 1/p62 up-regulation prevents aggregation of
RT ubiquitinated proteins induced by prostaglandin J2 without reducing its
RT neurotoxicity.";
RL Mol. Cell. Neurosci. 29:222-231(2005).
RN [30]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-148, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [31]
RP INTERACTION WITH NBR1 AND TRIM55, PHOSPHORYLATION, DOMAINS, AND FUNCTION.
RX PubMed=15802564; DOI=10.1126/science.1110463;
RA Lange S., Xiang F., Yakovenko A., Vihola A., Hackman P., Rostkova E.,
RA Kristensen J., Brandmeier B., Franzen G., Hedberg B., Gunnarsson L.G.,
RA Hughes S.M., Marchand S., Sejersen T., Richard I., Edstroem L., Ehler E.,
RA Udd B., Gautel M.;
RT "The kinase domain of titin controls muscle gene expression and protein
RT turnover.";
RL Science 308:1599-1603(2005).
RN [32]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-332, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [33]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-269 AND SER-272, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [34]
RP INTERACTION WITH GABARAP; GABARAPL1; GABARAPL2; MAP1LC3A AND MAP1LC3B, AND
RP MUTAGENESIS OF 323-GLU-GLU-324; SER-332; 335-ASP--ASP-337; TRP-338 AND
RP SER-342.
RX PubMed=17580304; DOI=10.1074/jbc.m702824200;
RA Pankiv S., Clausen T.H., Lamark T., Brech A., Bruun J.A., Outzen H.,
RA Overvatn A., Bjorkoy G., Johansen T.;
RT "p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of
RT ubiquitinated protein aggregates by autophagy.";
RL J. Biol. Chem. 282:24131-24145(2007).
RN [35]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-269 AND SER-272, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [36]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-170; THR-269; SER-272;
RP SER-328; SER-332 AND SER-366, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [37]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [38]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [39]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-355 AND SER-361, AND
RP IDENTIFICATION BY 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 [40]
RP FUNCTION, INTERACTION WITH WDFY3, AND SUBCELLULAR LOCATION.
RX PubMed=20168092; DOI=10.4161/auto.6.3.11226;
RA Clausen T.H., Lamark T., Isakson P., Finley K., Larsen K.B., Brech A.,
RA Overvatn A., Stenmark H., Bjorkoy G., Simonsen A., Johansen T.;
RT "p62/SQSTM1 and ALFY interact to facilitate the formation of p62
RT bodies/ALIS and their degradation by autophagy.";
RL Autophagy 6:330-344(2010).
RN [41]
RP INTERACTION WITH KEAP1.
RX PubMed=20495340; DOI=10.4161/auto.6.5.12189;
RA Fan W., Tang Z., Chen D., Moughon D., Ding X., Chen S., Zhu M., Zhong Q.;
RT "Keap1 facilitates p62-mediated ubiquitin aggregate clearance via
RT autophagy.";
RL Autophagy 6:614-621(2010).
RN [42]
RP FUNCTION, INTERACTION WITH KEAP1, INDUCTION, AND MUTAGENESIS OF ASP-347;
RP THR-350; GLY-351 AND GLU-352.
RX PubMed=20452972; DOI=10.1074/jbc.m110.118976;
RA Jain A., Lamark T., Sjoettem E., Larsen K.B., Awuh J.A., Oevervatn A.,
RA McMahon M., Hayes J.D., Johansen T.;
RT "p62/SQSTM1 is a target gene for transcription factor NRF2 and creates a
RT positive feedback loop by inducing antioxidant response element-driven gene
RT transcription.";
RL J. Biol. Chem. 285:22576-22591(2010).
RN [43]
RP INTERACTION WITH FHOD3.
RX PubMed=21149568; DOI=10.1083/jcb.201005060;
RA Iskratsch T., Lange S., Dwyer J., Kho A.L., dos Remedios C., Ehler E.;
RT "Formin follows function: a muscle-specific isoform of FHOD3 is regulated
RT by CK2 phosphorylation and promotes myofibril maintenance.";
RL J. Cell Biol. 191:1159-1172(2010).
RN [44]
RP INTERACTION WITH TRIM5, AND SUBCELLULAR LOCATION.
RX PubMed=20357094; DOI=10.1128/jvi.02412-09;
RA O'Connor C., Pertel T., Gray S., Robia S.L., Bakowska J.C., Luban J.,
RA Campbell E.M.;
RT "p62/sequestosome-1 associates with and sustains the expression of
RT retroviral restriction factor TRIM5alpha.";
RL J. Virol. 84:5997-6006(2010).
RN [45]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-170; SER-207; SER-249;
RP SER-266; SER-272 AND SER-332, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [46]
RP INVOLVEMENT IN FTDALS3, AND VARIANTS FTDALS3 VAL-33; ILE-153; LEU-228;
RP LYS-238 DEL; PRO-318; CYS-321; PRO-370; LEU-392; SER-411 AND ARG-425.
RX PubMed=22084127; DOI=10.1001/archneurol.2011.250;
RA Fecto F., Yan J., Vemula S.P., Liu E., Yang Y., Chen W., Zheng J.G.,
RA Shi Y., Siddique N., Arrat H., Donkervoort S., Ajroud-Driss S., Sufit R.L.,
RA Heller S.L., Deng H.X., Siddique T.;
RT "SQSTM1 mutations in familial and sporadic amyotrophic lateral sclerosis.";
RL Arch. Neurol. 68:1440-1446(2011).
RN [47]
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 [48]
RP IDENTIFICATION IN A COMPLEX WITH ZFAND5 AND UBIQUITIN, AND SUBCELLULAR
RP LOCATION.
RX PubMed=21923101; DOI=10.1021/bi201137e;
RA Garner T.P., Strachan J., Shedden E.C., Long J.E., Cavey J.R., Shaw B.,
RA Layfield R., Searle M.S.;
RT "Independent interactions of ubiquitin-binding domains in a ubiquitin-
RT mediated ternary complex.";
RL Biochemistry 50:9076-9087(2011).
RN [49]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-272, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [50]
RP FUNCTION.
RX PubMed=22622177; DOI=10.4161/auto.19381;
RA Taillebourg E., Gregoire I., Viargues P., Jacomin A.C., Thevenon D.,
RA Faure M., Fauvarque M.O.;
RT "The deubiquitinating enzyme USP36 controls selective autophagy activation
RT by ubiquitinated proteins.";
RL Autophagy 8:767-779(2012).
RN [51]
RP INTERACTION WITH TRIM13, AND SUBCELLULAR LOCATION.
RX PubMed=22178386; DOI=10.1016/j.bbamcr.2011.11.015;
RA Tomar D., Singh R., Singh A.K., Pandya C.D., Singh R.;
RT "TRIM13 regulates ER stress induced autophagy and clonogenic ability of the
RT cells.";
RL Biochim. Biophys. Acta 1823:316-326(2012).
RN [52]
RP INTERACTION WITH MAP1LC3A.
RX PubMed=22421968; DOI=10.1038/cdd.2012.30;
RA Seillier M., Peuget S., Gayet O., Gauthier C., N'guessan P., Monte M.,
RA Carrier A., Iovanna J.L., Dusetti N.J.;
RT "TP53INP1, a tumor suppressor, interacts with LC3 and ATG8-family proteins
RT through the LC3-interacting region (LIR) and promotes autophagy-dependent
RT cell death.";
RL Cell Death Differ. 19:1525-1535(2012).
RN [53]
RP INTERACTION WITH TRIM50, AND SUBCELLULAR LOCATION.
RX PubMed=22792322; DOI=10.1371/journal.pone.0040440;
RA Fusco C., Micale L., Egorov M., Monti M., D'Addetta E.V., Augello B.,
RA Cozzolino F., Calcagni A., Fontana A., Polishchuk R.S., Didelot G.,
RA Reymond A., Pucci P., Merla G.;
RT "The E3-ubiquitin ligase TRIM50 interacts with HDAC6 and p62, and promotes
RT the sequestration and clearance of ubiquitinated proteins into the
RT aggresome.";
RL PLoS ONE 7:E40440-E40440(2012).
RN [54]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, ACETYLATION [LARGE SCALE
RP ANALYSIS] AT ALA-2 (ISOFORM 2), CLEAVAGE OF INITIATOR METHIONINE [LARGE
RP SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]
RP (ISOFORM 2), AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [55]
RP FUNCTION.
RX PubMed=24128730; DOI=10.4161/auto.26085;
RA Isakson P., Lystad A.H., Breen K., Koster G., Stenmark H., Simonsen A.;
RT "TRAF6 mediates ubiquitination of KIF23/MKLP1 and is required for midbody
RT ring degradation by selective autophagy.";
RL Autophagy 9:1955-1964(2013).
RN [56]
RP INTERACTION WITH SESN1 AND SESN2.
RX PubMed=23274085; DOI=10.1016/j.cmet.2012.12.002;
RA Bae S.H., Sung S.H., Oh S.Y., Lim J.M., Lee S.K., Park Y.N., Lee H.E.,
RA Kang D., Rhee S.G.;
RT "Sestrins activate Nrf2 by promoting p62-dependent autophagic degradation
RT of Keap1 and prevent oxidative liver damage.";
RL Cell Metab. 17:73-84(2013).
RN [57]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-170; THR-269; SER-272;
RP SER-332 AND SER-366, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [58]
RP INVOLVEMENT IN FTDALS3, AND VARIANTS FTDALS3 VAL-33; VAL-381; LEU-387 AND
RP LEU-392.
RX PubMed=24042580; DOI=10.1001/jamaneurol.2013.3849;
RG French Clinical and Genetic Research Network on FTD/FTD-ALS;
RA Le Ber I., Camuzat A., Guerreiro R., Bouya-Ahmed K., Bras J., Nicolas G.,
RA Gabelle A., Didic M., De Septenville A., Millecamps S., Lenglet T.,
RA Latouche M., Kabashi E., Campion D., Hannequin D., Hardy J., Brice A.;
RT "SQSTM1 mutations in French patients with frontotemporal dementia or
RT frontotemporal dementia with amyotrophic lateral sclerosis.";
RL JAMA Neurol. 70:1403-1410(2013).
RN [59]
RP LIR MOTIF.
RX PubMed=23908376; DOI=10.1242/jcs.126128;
RA Birgisdottir A.B., Lamark T., Johansen T.;
RT "The LIR motif - crucial for selective autophagy.";
RL J. Cell Sci. 126:3237-3247(2013).
RN [60]
RP INTERACTION WITH MAP1LC3B.
RX PubMed=24089205; DOI=10.1038/nature12606;
RA Tang Z., Lin M.G., Stowe T.R., Chen S., Zhu M., Stearns T., Franco B.,
RA Zhong Q.;
RT "Autophagy promotes primary ciliogenesis by removing OFD1 from centriolar
RT satellites.";
RL Nature 502:254-257(2013).
RN [61]
RP INTERACTION WITH TRIM5.
RX PubMed=25127057; DOI=10.1016/j.devcel.2014.06.013;
RA Mandell M.A., Jain A., Arko-Mensah J., Chauhan S., Kimura T., Dinkins C.,
RA Silvestri G., Munch J., Kirchhoff F., Simonsen A., Wei Y., Levine B.,
RA Johansen T., Deretic V.;
RT "TRIM proteins regulate autophagy and can target autophagic substrates by
RT direct recognition.";
RL Dev. Cell 30:394-409(2014).
RN [62]
RP INTERACTION WITH SESN2 AND ULK1, AND PHOSPHORYLATION AT SER-403 BY ULK1.
RX PubMed=25040165; DOI=10.1111/febs.12905;
RA Ro S.H., Semple I.A., Park H., Park H., Park H.W., Kim M., Kim J.S.,
RA Lee J.H.;
RT "Sestrin2 promotes Unc-51-like kinase 1 mediated phosphorylation of
RT p62/sequestosome-1.";
RL FEBS J. 281:3816-3827(2014).
RN [63]
RP INTERACTION WITH GABARAP, AND MUTAGENESIS OF TRP-338.
RX PubMed=24668264; DOI=10.1002/embr.201338003;
RA Lystad A.H., Ichimura Y., Takagi K., Yang Y., Pankiv S., Kanegae Y.,
RA Kageyama S., Suzuki M., Saito I., Mizushima T., Komatsu M., Simonsen A.;
RT "Structural determinants in GABARAP required for the selective binding and
RT recruitment of ALFY to LC3B-positive structures.";
RL EMBO Rep. 15:557-565(2014).
RN [64]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-24; SER-176; SER-233; SER-306
RP AND SER-366, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [65]
RP INTERACTION WITH UBD.
RX PubMed=25422469; DOI=10.1073/pnas.1403383111;
RA Theng S.S., Wang W., Mah W.C., Chan C., Zhuo J., Gao Y., Qin H., Lim L.,
RA Chong S.S., Song J., Lee C.G.;
RT "Disruption of FAT10-MAD2 binding inhibits tumor progression.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:E5282-E5291(2014).
RN [66]
RP DISEASE, AND CHROMOSOMAL TRANSLOCATION WITH NU214.
RX PubMed=20851865; DOI=10.3324/haematol.2010.029769;
RA Gorello P., La Starza R., Di Giacomo D., Messina M., Puzzolo M.C.,
RA Crescenzi B., Santoro A., Chiaretti S., Mecucci C.;
RT "SQSTM1-NUP214: a new gene fusion in adult T-cell acute lymphoblastic
RT leukemia.";
RL Haematologica 95:2161-2163(2010).
RN [67]
RP INVOLVEMENT IN FTDALS3, AND VARIANT FTDALS3 LYS-238 DEL.
RX PubMed=25114083; DOI=10.3233/jad-141512;
RA Boutoleau-Bretonniere C., Camuzat A., Le Ber I., Bouya-Ahmed K.,
RA Guerreiro R., Deruet A.L., Evrard C., Bras J., Lamy E., Auffray-Calvier E.,
RA Pallardy A., Hardy J., Brice A., Derkinderen P., Vercelletto M.;
RT "A phenotype of atypical apraxia of speech in a family carrying SQSTM1
RT mutation.";
RL J. Alzheimers Dis. 43:625-630(2015).
RN [68]
RP INVOLVEMENT IN DMRV.
RX PubMed=26208961; DOI=10.1212/wnl.0000000000001864;
RA Bucelli R.C., Arhzaouy K., Pestronk A., Pittman S.K., Rojas L., Sue C.M.,
RA Evilae A., Hackman P., Udd B., Harms M.B., Weihl C.C.;
RT "SQSTM1 splice site mutation in distal myopathy with rimmed vacuoles.";
RL Neurology 85:665-674(2015).
RN [69]
RP INVOLVEMENT IN NADGP.
RX PubMed=27545679; DOI=10.1016/j.ajhg.2016.06.026;
RA Haack T.B., Ignatius E., Calvo-Garrido J., Iuso A., Isohanni P.,
RA Maffezzini C., Loennqvist T., Suomalainen A., Gorza M., Kremer L.S.,
RA Graf E., Hartig M., Berutti R., Paucar M., Svenningsson P., Stranneheim H.,
RA Brandberg G., Wedell A., Kurian M.A., Hayflick S.A., Venco P., Tiranti V.,
RA Strom T.M., Dichgans M., Horvath R., Holinski-Feder E., Freyer C.,
RA Meitinger T., Prokisch H., Senderek J., Wredenberg A., Carroll C.J.,
RA Klopstock T.;
RT "Absence of the autophagy adaptor SQSTM1/p62 causes childhood-onset
RT neurodegeneration with ataxia, dystonia, and gaze palsy.";
RL Am. J. Hum. Genet. 99:735-743(2016).
RN [70]
RP FUNCTION, AND UBIQUITINATION.
RX PubMed=27368102; DOI=10.1016/j.cell.2016.05.078;
RA Jongsma M.L., Berlin I., Wijdeven R.H., Janssen L., Janssen G.M.,
RA Garstka M.A., Janssen H., Mensink M., van Veelen P.A., Spaapen R.M.,
RA Neefjes J.;
RT "An ER-associated pathway defines endosomal architecture for controlled
RT cargo transport.";
RL Cell 166:152-166(2016).
RN [71]
RP UBIQUITINATION, AND FUNCTION.
RX PubMed=27880896; DOI=10.1016/j.celrep.2016.11.005;
RA Heath R.J., Goel G., Baxt L.A., Rush J.S., Mohanan V., Paulus G.L.C.,
RA Jani V., Lassen K.G., Xavier R.J.;
RT "RNF166 Determines Recruitment of Adaptor Proteins during Antibacterial
RT Autophagy.";
RL Cell Rep. 17:2183-2194(2016).
RN [72]
RP FUNCTION, UBIQUITINATION AT LYS-420, AND MUTAGENESIS OF LYS-420.
RX PubMed=28380357; DOI=10.1016/j.celrep.2017.03.030;
RA Lee Y., Chou T.F., Pittman S.K., Keith A.L., Razani B., Weihl C.C.;
RT "Keap1/cullin3 modulates p62/SQSTM1 activity via UBA domain
RT ubiquitination.";
RL Cell Rep. 19:188-202(2017).
RN [73]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-435, AND IDENTIFICATION BY MASS
RP 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 [74]
RP INTERACTION WITH TRIM16.
RX PubMed=30143514; DOI=10.15252/embj.201798358;
RA Jena K.K., Kolapalli S.P., Mehto S., Nath P., Das B., Sahoo P.K., Ahad A.,
RA Syed G.H., Raghav S.K., Senapati S., Chauhan S., Chauhan S.;
RT "TRIM16 controls assembly and degradation of protein aggregates by
RT modulating the p62-NRF2 axis and autophagy.";
RL EMBO J. 37:0-0(2018).
RN [75]
RP INTERACTION WITH LRRC25.
RX PubMed=29288164; DOI=10.15252/embj.201796781;
RA Du Y., Duan T., Feng Y., Liu Q., Lin M., Cui J., Wang R.F.;
RT "LRRC25 inhibits type I IFN signaling by targeting ISG15-associated RIG-I
RT for autophagic degradation.";
RL EMBO J. 37:351-366(2018).
RN [76]
RP FUNCTION, INTERACTION WITH WDR81, AND DOMAIN.
RX PubMed=28404643; DOI=10.1083/jcb.201608039;
RA Liu X., Li Y., Wang X., Xing R., Liu K., Gan Q., Tang C., Gao Z., Jian Y.,
RA Luo S., Guo W., Yang C.;
RT "The BEACH-containing protein WDR81 coordinates p62 and LC3C to promote
RT aggrephagy.";
RL J. Cell Biol. 216:1301-1320(2017).
RN [77]
RP INTERACTION WITH TRIM23.
RX PubMed=28871090; DOI=10.1038/s41564-017-0017-2;
RA Sparrer K.M.J., Gableske S., Zurenski M.A., Parker Z.M., Full F.,
RA Baumgart G.J., Kato J., Pacheco-Rodriguez G., Liang C., Pornillos O.,
RA Moss J., Vaughan M., Gack M.U.;
RT "TRIM23 mediates virus-induced autophagy via activation of TBK1.";
RL Nat. Microbiol. 2:1543-1557(2017).
RN [78]
RP FUNCTION, PHOSPHORYLATION AT SER-403, AND MUTAGENESIS OF SER-403.
RX PubMed=29496741; DOI=10.15252/embj.201797858;
RA Prabakaran T., Bodda C., Krapp C., Zhang B.C., Christensen M.H., Sun C.,
RA Reinert L., Cai Y., Jensen S.B., Skouboe M.K., Nyengaard J.R.,
RA Thompson C.B., Lebbink R.J., Sen G.C., van Loo G., Nielsen R., Komatsu M.,
RA Nejsum L.N., Jakobsen M.R., Gyrd-Hansen M., Paludan S.R.;
RT "Attenuation of cGAS-STING signaling is mediated by a p62/SQSTM1-dependent
RT autophagy pathway activated by TBK1.";
RL EMBO J. 37:0-0(2018).
RN [79]
RP INTERACTION WITH CYLD.
RX PubMed=32185393; DOI=10.1093/brain/awaa039;
RA Dobson-Stone C., Hallupp M., Shahheydari H., Ragagnin A.M.G.,
RA Chatterton Z., Carew-Jones F., Shepherd C.E., Stefen H., Paric E., Fath T.,
RA Thompson E.M., Blumbergs P., Short C.L., Field C.D., Panegyres P.K.,
RA Hecker J., Nicholson G., Shaw A.D., Fullerton J.M., Luty A.A.,
RA Schofield P.R., Brooks W.S., Rajan N., Bennett M.F., Bahlo M.,
RA Landers J.E., Piguet O., Hodges J.R., Halliday G.M., Topp S.D., Smith B.N.,
RA Shaw C.E., McCann E., Fifita J.A., Williams K.L., Atkin J.D., Blair I.P.,
RA Kwok J.B.;
RT "CYLD is a causative gene for frontotemporal dementia - amyotrophic lateral
RT sclerosis.";
RL Brain 143:783-799(2020).
RN [80]
RP FUNCTION, AND INTERACTION WITH MOAP1.
RX PubMed=33393215; DOI=10.15252/embr.202050854;
RA Tan C.T., Chang H.C., Zhou Q., Yu C., Fu N.Y., Sabapathy K., Yu V.C.;
RT "MOAP-1-mediated dissociation of p62/SQSTM1 bodies releases Keap1 and
RT suppresses Nrf2 signaling.";
RL EMBO Rep. 22:e50854-e50854(2021).
RN [81]
RP UBIQUITINATION AT LYS-435.
RX PubMed=33472082; DOI=10.1016/j.celrep.2020.108659;
RA Cremer T., Jongsma M.L.M., Trulsson F., Vertegaal A.C.O., Neefjes J.,
RA Berlin I.;
RT "The ER-embedded UBE2J1/RNF26 ubiquitylation complex exerts spatiotemporal
RT control over the endolysosomal pathway.";
RL Cell Rep. 34:108659-108659(2021).
RN [82]
RP STRUCTURE BY NMR OF 387-436, CHARACTERIZATION OF VARIANT LEU-392, AND
RP DOMAIN.
RX PubMed=12857745; DOI=10.1074/jbc.m307416200;
RA Ciani B., Layfield R., Cavey J.R., Sheppard P.W., Searle M.S.;
RT "Structure of the ubiquitin-associated domain of p62 (SQSTM1) and
RT implications for mutations that cause Paget's disease of bone.";
RL J. Biol. Chem. 278:37409-37412(2003).
RN [83]
RP STRUCTURE BY NMR OF 387-436, AND INTERACTION WITH UBIQUITIN.
RX PubMed=18083707; DOI=10.1074/jbc.m704973200;
RA Long J., Gallagher T.R., Cavey J.R., Sheppard P.W., Ralston S.H.,
RA Layfield R., Searle M.S.;
RT "Ubiquitin recognition by the ubiquitin-associated domain of p62 involves a
RT novel conformational switch.";
RL J. Biol. Chem. 283:5427-5440(2008).
RN [84]
RP STRUCTURE BY NMR OF 387-436.
RX PubMed=17932931; DOI=10.1002/prot.21692;
RA Evans C.L., Long J.E., Gallagher T.R., Hirst J.D., Searle M.S.;
RT "Conformation and dynamics of the three-helix bundle UBA domain of p62 from
RT experiment and simulation.";
RL Proteins 71:227-240(2008).
RN [85]
RP STRUCTURE BY NMR OF 387-436, SUBUNIT, FUNCTION, MUTAGENESIS OF GLU-409 AND
RP GLY-410, AND CHARACTERIZATION OF VARIANT PDB3 ARG-425.
RX PubMed=19931284; DOI=10.1016/j.jmb.2009.11.032;
RA Long J., Garner T.P., Pandya M.J., Craven C.J., Chen P., Shaw B.,
RA Williamson M.P., Layfield R., Searle M.S.;
RT "Dimerisation of the UBA domain of p62 inhibits ubiquitin binding and
RT regulates NF-kappaB signalling.";
RL J. Mol. Biol. 396:178-194(2010).
RN [86]
RP VARIANT PDB3 LEU-392, AND VARIANTS VAL-117 AND GLN-274.
RX PubMed=11992264; DOI=10.1086/340731;
RA Laurin N., Brown J.P., Morissette J., Raymond V.;
RT "Recurrent mutation of the gene encoding sequestosome 1 (SQSTM1/p62) in
RT Paget disease of bone.";
RL Am. J. Hum. Genet. 70:1582-1588(2002).
RN [87]
RP VARIANT PDB3 LEU-392.
RX PubMed=12374763; DOI=10.1093/hmg/11.22.2735;
RA Hocking L.J., Lucas G.J.A., Daroszewska A., Mangion J., Olavesen M.,
RA Cundy T., Nicholson G.C., Ward L., Bennett S.T., Wuyts W., Van Hul W.,
RA Ralston S.H.;
RT "Domain-specific mutations in sequestosome 1 (SQSTM1) cause familial and
RT sporadic Paget's disease.";
RL Hum. Mol. Genet. 11:2735-2739(2002).
RN [88]
RP VARIANT PDB3 LEU-387.
RX PubMed=14584883; DOI=10.1359/jbmr.2003.18.10.1748;
RA Johnson-Pais T.L., Wisdom J.H., Weldon K.S., Cody J.D., Hansen M.F.,
RA Singer F.R., Leach R.J.;
RT "Three novel mutations in SQSTM1 identified in familial Paget's disease of
RT bone.";
RL J. Bone Miner. Res. 18:1748-1753(2003).
RN [89]
RP VARIANTS PDB3 LEU-392; PRO-399; THR-404 AND ARG-425.
RX PubMed=15146436; DOI=10.1002/art.20224;
RA Eekhoff E.W.M., Karperien M., Houtsma D., Zwinderman A.H., Dragoiescu C.,
RA Kneppers A.L.J., Papapoulos S.E.;
RT "Familial Paget's disease in The Netherlands: occurrence, identification of
RT new mutations in the sequestosome 1 gene, and their clinical
RT associations.";
RL Arthritis Rheum. 50:1650-1654(2004).
RN [90]
RP VARIANT PDB3 LEU-392.
RX PubMed=15207768; DOI=10.1016/j.bone.2004.01.010;
RA Good D.A., Busfield F., Fletcher B.H., Lovelock P.K., Duffy D.L.,
RA Kesting J.B., Andersen J., Shaw J.T.E.;
RT "Identification of SQSTM1 mutations in familial Paget's disease in
RT Australian pedigrees.";
RL Bone 35:277-282(2004).
RN [91]
RP VARIANTS PDB3 LEU-392; VAL-404 AND ARG-425.
RX PubMed=15125799; DOI=10.1359/jbmr.040203;
RA Falchetti A., Di Stefano M., Marini F., Del Monte F., Mavilia C.,
RA Strigoli D., De Feo M.L., Isaia G., Masi L., Amedei A., Cioppi F.,
RA Ghinoi V., Maddali Bongi S., Di Fede G., Sferrazza C., Rini G.B.,
RA Melchiorre D., Matucci-Cerinic M., Brandi M.L.;
RT "Two novel mutations at exon 8 of the Sequestosome 1 (SQSTM1) gene in an
RT Italian series of patients affected by Paget's disease of bone (PDB).";
RL J. Bone Miner. Res. 19:1013-1017(2004).
RN [92]
RP VARIANTS PDB3 VAL-404; SER-411 AND ARG-425, AND CHARACTERIZATION OF
RP VARIANTS VAL-404; SER-411 AND ARG-425.
RX PubMed=15176995; DOI=10.1359/jbmr.0403015;
RA Hocking L.J., Lucas G.J.A., Daroszewska A., Cundy T., Nicholson G.C.,
RA Donath J., Walsh J.P., Finlayson C., Cavey J.R., Ciani B., Sheppard P.W.,
RA Searle M.S., Layfield R., Ralston S.H.;
RT "Novel UBA domain mutations of SQSTM1 in Paget's disease of bone: genotype
RT phenotype correlation, functional analysis, and structural consequences.";
RL J. Bone Miner. Res. 19:1122-1127(2004).
RN [93]
RP VARIANT GLU-238, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=17488105; DOI=10.1021/pr0700908;
RA Bunger M.K., Cargile B.J., Sevinsky J.R., Deyanova E., Yates N.A.,
RA Hendrickson R.C., Stephenson J.L. Jr.;
RT "Detection and validation of non-synonymous coding SNPs from orthogonal
RT analysis of shotgun proteomics data.";
RL J. Proteome Res. 6:2331-2340(2007).
RN [94]
RP INVOLVEMENT IN FTDALS3, VARIANTS FTDALS3 VAL-16; VAL-33; GLU-80; MET-90;
RP TRP-107; ASN-129; CYS-212; VAL-219; PRO-226; LEU-228; THR-232; LYS-238 DEL;
RP ASN-258; CYS-321; GLY-329; LEU-348; LEU-387; LEU-392 AND PRO-430, AND
RP VARIANTS VAL-17; ARG-103; GLN-107; TYR-108; HIS-110; VAL-117; SER-118;
RP GLY-119; SER-125; CYS-139; ILE-153; LEU-180; HIS-217; GLU-238;
RP 265-SER-ARG-266 DELINS SER-ARG; ASP-274; ILE-278; VAL-308; LYS-319; GLY-334
RP DEL; THR-349 AND LEU-439.
RX PubMed=24899140; DOI=10.1007/s00401-014-1298-7;
RA van der Zee J., Van Langenhove T., Kovacs G.G., Dillen L., Deschamps W.,
RA Engelborghs S., Matej R., Vandenbulcke M., Sieben A., Dermaut B., Smets K.,
RA Van Damme P., Merlin C., Laureys A., Van Den Broeck M., Mattheijssens M.,
RA Peeters K., Benussi L., Binetti G., Ghidoni R., Borroni B., Padovani A.,
RA Archetti S., Pastor P., Razquin C., Ortega-Cubero S., Hernandez I.,
RA Boada M., Ruiz A., de Mendonca A., Miltenberger-Miltenyi G., do Couto F.S.,
RA Sorbi S., Nacmias B., Bagnoli S., Graff C., Chiang H.H., Thonberg H.,
RA Perneczky R., Diehl-Schmid J., Alexopoulos P., Frisoni G.B., Bonvicini C.,
RA Synofzik M., Maetzler W., vom Hagen J.M., Schoels L., Haack T.B.,
RA Strom T.M., Prokisch H., Dols-Icardo O., Clarimon J., Lleo A., Santana I.,
RA Almeida M.R., Santiago B., Heneka M.T., Jessen F., Ramirez A.,
RA Sanchez-Valle R., Llado A., Gelpi E., Sarafov S., Tournev I., Jordanova A.,
RA Parobkova E., Fabrizi G.M., Testi S., Salmon E., Stroebel T., Santens P.,
RA Robberecht W., De Jonghe P., Martin J.J., Cras P., Vandenberghe R.,
RA De Deyn P.P., Cruts M., Sleegers K., Van Broeckhoven C.;
RT "Rare mutations in SQSTM1 modify susceptibility to frontotemporal lobar
RT degeneration.";
RL Acta Neuropathol. 128:397-410(2014).
CC -!- FUNCTION: Autophagy receptor required for selective macroautophagy
CC (aggrephagy). Functions as a bridge between polyubiquitinated cargo and
CC autophagosomes. Interacts directly with both the cargo to become
CC degraded and an autophagy modifier of the MAP1 LC3 family
CC (PubMed:16286508, PubMed:20168092, PubMed:24128730, PubMed:28404643,
CC PubMed:22622177). Along with WDFY3, involved in the formation and
CC autophagic degradation of cytoplasmic ubiquitin-containing inclusions
CC (p62 bodies, ALIS/aggresome-like induced structures). Along with WDFY3,
CC required to recruit ubiquitinated proteins to PML bodies in the nucleus
CC (PubMed:24128730, PubMed:20168092). May regulate the activation of
CC NFKB1 by TNF-alpha, nerve growth factor (NGF) and interleukin-1. May
CC play a role in titin/TTN downstream signaling in muscle cells. May
CC regulate signaling cascades through ubiquitination. Adapter that
CC mediates the interaction between TRAF6 and CYLD (By similarity). May be
CC involved in cell differentiation, apoptosis, immune response and
CC regulation of K(+) channels. Involved in endosome organization by
CC retaining vesicles in the perinuclear cloud: following ubiquitination
CC by RNF26, attracts specific vesicle-associated adapters, forming a
CC molecular bridge that restrains cognate vesicles in the perinuclear
CC region and organizes the endosomal pathway for efficient cargo
CC transport (PubMed:27368102). Promotes relocalization of 'Lys-63'-linked
CC ubiquitinated STING1 to autophagosomes (PubMed:29496741). Acts as an
CC activator of the NFE2L2/NRF2 pathway via interaction with KEAP1:
CC interaction inactivates the BCR(KEAP1) complex, promoting nuclear
CC accumulation of NFE2L2/NRF2 and subsequent expression of cytoprotective
CC genes (PubMed:20452972, PubMed:28380357, PubMed:33393215).
CC {ECO:0000250|UniProtKB:O08623, ECO:0000250|UniProtKB:Q64337,
CC ECO:0000269|PubMed:10356400, ECO:0000269|PubMed:10747026,
CC ECO:0000269|PubMed:11244088, ECO:0000269|PubMed:12471037,
CC ECO:0000269|PubMed:15340068, ECO:0000269|PubMed:15802564,
CC ECO:0000269|PubMed:15911346, ECO:0000269|PubMed:15953362,
CC ECO:0000269|PubMed:16079148, ECO:0000269|PubMed:16286508,
CC ECO:0000269|PubMed:19931284, ECO:0000269|PubMed:20168092,
CC ECO:0000269|PubMed:20452972, ECO:0000269|PubMed:22622177,
CC ECO:0000269|PubMed:24128730, ECO:0000269|PubMed:27368102,
CC ECO:0000269|PubMed:28380357, ECO:0000269|PubMed:28404643,
CC ECO:0000269|PubMed:29496741, ECO:0000269|PubMed:33393215}.
CC -!- SUBUNIT: Homooligomer or heterooligomer; may form homotypic arrays.
CC Dimerization interferes with ubiquitin binding. Interacts directly with
CC PRKCI and PRKCZ (Probable). Forms ternary complexes with PRKCZ and
CC KCNAB2 or PRKCZ and GABBR3. Also interacts with KCNAB1, GABRR1, GABRR2
CC and GABRR3. Forms an NGF-induced complex with IKBKB, PRKCI and TRAF6
CC (By similarity). Interacts with EBI3, LCK, RASA1, PRKCZ, PRKCI, NR2F2,
CC NTRK1, NTRK2, NTRK3, NBR1, MAP2K5, TRIM13, TRIM55 and MAPKAPK5.
CC Interacts with the proteasome subunits PSMD4 and PSMC2. Interacts with
CC K63-polyubiquitinated MAPT/TAU. Interacts with IKBKB through PRKCZ and
CC PRKCI. Interacts with NGFR through TRAF6 and bridges that complex to
CC NTRK1. Forms a complex with MAP2K5 and PRKCZ or PRKCI. Component of a
CC ternary complex with PAWR and PRKCZ. Upon TNF-alpha stimulation,
CC interacts with RIPK1 probably bridging IKBKB to the TNF-R1 complex
CC composed of TNF-R1/TNFRSF1A, TRADD and RIPK1. Forms a complex with
CC JUB/Ajuba, PRKCZ and TRAF6. Interacts with TRAF6 (By similarity).
CC Interacts with CYLD (PubMed:32185393). Identified in a complex with
CC TRAF6 and CYLD (By similarity). Identified in a heterotrimeric complex
CC with ubiquitin and ZFAND5, where ZFAND5 and SQSTM1 both interact with
CC the same ubiquitin molecule. Directly interacts with MAP1LC3A and
CC MAP1LC3B, as well as with other MAP1 LC3 family members, including
CC GABARAP, GABARAPL1 and GABARAPL2; these interactions are necessary for
CC the recruitment MAP1 LC3 family members to inclusion bodies containing
CC polyubiquitinated protein aggregates and for their degradation by
CC autophagy. Interacts with FHOD3. Interacts with TRMI5. Interacts with
CC SESN1 (PubMed:23274085). Interacts with SESN2 (PubMed:23274085,
CC PubMed:25040165). Interacts with ULK1 (PubMed:25040165). Interacts with
CC UBD (PubMed:25422469). Interacts with WDR81; the interaction is direct
CC and regulates the interaction of SQSTM1 with ubiquitinated proteins
CC (PubMed:28404643). Interacts with WDFY3; this interaction is required
CC to recruit WDFY3 to cytoplasmic bodies and to PML bodies
CC (PubMed:20168092). Interacts with TRIM23 (PubMed:28871090). Interacts
CC with LRRC25 (PubMed:29288164). Interacts with TRIM50 (PubMed:22792322).
CC Interacts with TRIM16 (PubMed:30143514). Interacts with STING1; leading
CC to relocalization of STING1 to autophagosomes. Interacts (when
CC phosphorylated at Ser-349) with KEAP1; the interaction is direct and
CC inactivates the BCR(KEAP1) complex by sequestering KEAP1 in inclusion
CC bodies, promoting its degradation (PubMed:20495340, PubMed:20452972).
CC Interacts with GBP1 (By similarity). Interacts with MOAP1; promoting
CC dissociation of SQSTM1 inclusion bodies that sequester KEAP1
CC (PubMed:33393215). {ECO:0000250|UniProtKB:O08623,
CC ECO:0000250|UniProtKB:Q64337, ECO:0000269|PubMed:10356400,
CC ECO:0000269|PubMed:10708586, ECO:0000269|PubMed:10747026,
CC ECO:0000269|PubMed:11244088, ECO:0000269|PubMed:11755531,
CC ECO:0000269|PubMed:12471037, ECO:0000269|PubMed:12813044,
CC ECO:0000269|PubMed:12887891, ECO:0000269|PubMed:15340068,
CC ECO:0000269|PubMed:15802564, ECO:0000269|PubMed:15870274,
CC ECO:0000269|PubMed:15953362, ECO:0000269|PubMed:16286508,
CC ECO:0000269|PubMed:17580304, ECO:0000269|PubMed:18083707,
CC ECO:0000269|PubMed:19931284, ECO:0000269|PubMed:20168092,
CC ECO:0000269|PubMed:20357094, ECO:0000269|PubMed:20452972,
CC ECO:0000269|PubMed:20495340, ECO:0000269|PubMed:21149568,
CC ECO:0000269|PubMed:21923101, ECO:0000269|PubMed:22178386,
CC ECO:0000269|PubMed:22421968, ECO:0000269|PubMed:22792322,
CC ECO:0000269|PubMed:23274085, ECO:0000269|PubMed:24089205,
CC ECO:0000269|PubMed:24668264, ECO:0000269|PubMed:25040165,
CC ECO:0000269|PubMed:25127057, ECO:0000269|PubMed:25422469,
CC ECO:0000269|PubMed:28404643, ECO:0000269|PubMed:28871090,
CC ECO:0000269|PubMed:29288164, ECO:0000269|PubMed:29496741,
CC ECO:0000269|PubMed:30143514, ECO:0000269|PubMed:32185393,
CC ECO:0000269|PubMed:33393215, ECO:0000269|PubMed:8551575,
CC ECO:0000269|PubMed:8618896, ECO:0000269|PubMed:8650207,
CC ECO:0000269|PubMed:8702753, ECO:0000269|PubMed:8910285,
CC ECO:0000269|PubMed:9566925, ECO:0000305}.
CC -!- INTERACTION:
CC Q13501; P05067: APP; NbExp=6; IntAct=EBI-307104, EBI-77613;
CC Q13501; P54253: ATXN1; NbExp=4; IntAct=EBI-307104, EBI-930964;
CC Q13501; O95817: BAG3; NbExp=3; IntAct=EBI-307104, EBI-747185;
CC Q13501; Q16543: CDC37; NbExp=8; IntAct=EBI-307104, EBI-295634;
CC Q13501; P34972: CNR2; NbExp=5; IntAct=EBI-307104, EBI-2835940;
CC Q13501; Q15038: DAZAP2; NbExp=4; IntAct=EBI-307104, EBI-724310;
CC Q13501; O14576-2: DYNC1I1; NbExp=3; IntAct=EBI-307104, EBI-25840445;
CC Q13501; Q2V2M9: FHOD3; NbExp=6; IntAct=EBI-307104, EBI-6395541;
CC Q13501; Q2V2M9-4: FHOD3; NbExp=4; IntAct=EBI-307104, EBI-6395505;
CC Q13501; O95166: GABARAP; NbExp=16; IntAct=EBI-307104, EBI-712001;
CC Q13501; Q9H0R8: GABARAPL1; NbExp=15; IntAct=EBI-307104, EBI-746969;
CC Q13501; P60520: GABARAPL2; NbExp=21; IntAct=EBI-307104, EBI-720116;
CC Q13501; P0DMV8: HSPA1A; NbExp=3; IntAct=EBI-307104, EBI-11052499;
CC Q13501; P42858: HTT; NbExp=8; IntAct=EBI-307104, EBI-466029;
CC Q13501; Q9Y6K9: IKBKG; NbExp=2; IntAct=EBI-307104, EBI-81279;
CC Q13501; Q14145: KEAP1; NbExp=19; IntAct=EBI-307104, EBI-751001;
CC Q13501; Q5S007: LRRK2; NbExp=18; IntAct=EBI-307104, EBI-5323863;
CC Q13501; Q9UDY8: MALT1; NbExp=2; IntAct=EBI-307104, EBI-1047372;
CC Q13501; Q9H492: MAP1LC3A; NbExp=12; IntAct=EBI-307104, EBI-720768;
CC Q13501; Q9GZQ8: MAP1LC3B; NbExp=26; IntAct=EBI-307104, EBI-373144;
CC Q13501; Q9BXW4: MAP1LC3C; NbExp=7; IntAct=EBI-307104, EBI-2603996;
CC Q13501; Q13163: MAP2K5; NbExp=5; IntAct=EBI-307104, EBI-307294;
CC Q13501; Q14596: NBR1; NbExp=7; IntAct=EBI-307104, EBI-742698;
CC Q13501; P04629: NTRK1; NbExp=2; IntAct=EBI-307104, EBI-1028226;
CC Q13501; Q96CV9: OPTN; NbExp=7; IntAct=EBI-307104, EBI-748974;
CC Q13501; P50542-3: PEX5; NbExp=2; IntAct=EBI-307104, EBI-12181987;
CC Q13501; Q9UGJ0: PRKAG2; NbExp=3; IntAct=EBI-307104, EBI-2959705;
CC Q13501; P41743: PRKCI; NbExp=10; IntAct=EBI-307104, EBI-286199;
CC Q13501; Q12923: PTPN13; NbExp=2; IntAct=EBI-307104, EBI-355227;
CC Q13501; P54725: RAD23A; NbExp=3; IntAct=EBI-307104, EBI-746453;
CC Q13501; P58004: SESN2; NbExp=9; IntAct=EBI-307104, EBI-3939642;
CC Q13501; Q96B97: SH3KBP1; NbExp=4; IntAct=EBI-307104, EBI-346595;
CC Q13501; P84022: SMAD3; NbExp=3; IntAct=EBI-307104, EBI-347161;
CC Q13501; P37840: SNCA; NbExp=3; IntAct=EBI-307104, EBI-985879;
CC Q13501; Q13501: SQSTM1; NbExp=10; IntAct=EBI-307104, EBI-307104;
CC Q13501; Q9UNE7: STUB1; NbExp=3; IntAct=EBI-307104, EBI-357085;
CC Q13501; Q9Y4K3: TRAF6; NbExp=4; IntAct=EBI-307104, EBI-359276;
CC Q13501; P07437: TUBB; NbExp=3; IntAct=EBI-307104, EBI-350864;
CC Q13501; P0CG48: UBC; NbExp=3; IntAct=EBI-307104, EBI-3390054;
CC Q13501; P11473: VDR; NbExp=4; IntAct=EBI-307104, EBI-286357;
CC Q13501; Q9UBQ0-2: VPS29; NbExp=3; IntAct=EBI-307104, EBI-11141397;
CC Q13501; P19544-6: WT1; NbExp=3; IntAct=EBI-307104, EBI-11745701;
CC Q13501; A0A024RC47: ZNF24; NbExp=3; IntAct=EBI-307104, EBI-25830832;
CC Q13501; A8K2U6; NbExp=3; IntAct=EBI-307104, EBI-25877771;
CC Q13501; P38182: ATG8; Xeno; NbExp=3; IntAct=EBI-307104, EBI-2684;
CC Q13501; Q9Z2X8: Keap1; Xeno; NbExp=2; IntAct=EBI-307104, EBI-647110;
CC Q13501; P28700: Rxra; Xeno; NbExp=3; IntAct=EBI-307104, EBI-346715;
CC Q13501; O70405: Ulk1; Xeno; NbExp=2; IntAct=EBI-307104, EBI-8390771;
CC Q13501; P12504: vif; Xeno; NbExp=2; IntAct=EBI-307104, EBI-779991;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:20168092,
CC ECO:0000269|PubMed:22792322}. Late endosome. Lysosome. Cytoplasmic
CC vesicle, autophagosome. Nucleus. Endoplasmic reticulum. Nucleus, PML
CC body {ECO:0000269|PubMed:20168092}. Cytoplasm, myofibril, sarcomere
CC {ECO:0000250}. Note=In cardiac muscle, localizes to the sarcomeric band
CC (By similarity). Commonly found in inclusion bodies containing
CC polyubiquitinated protein aggregates. In neurodegenerative diseases,
CC detected in Lewy bodies in Parkinson disease, neurofibrillary tangles
CC in Alzheimer disease, and HTT aggregates in Huntington disease. In
CC protein aggregate diseases of the liver, found in large amounts in
CC Mallory bodies of alcoholic and nonalcoholic steatohepatitis, hyaline
CC bodies in hepatocellular carcinoma, and in SERPINA1 aggregates.
CC Enriched in Rosenthal fibers of pilocytic astrocytoma. In the
CC cytoplasm, observed in both membrane-free ubiquitin-containing protein
CC aggregates (sequestosomes) and membrane-surrounded autophagosomes.
CC Colocalizes with TRIM13 in the perinuclear endoplasmic reticulum. Co-
CC localizes with TRIM5 in cytoplasmic bodies. When nuclear export is
CC blocked by treatment with leptomycin B, accumulates in PML bodies.
CC {ECO:0000269|PubMed:20168092}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q13501-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q13501-2; Sequence=VSP_015841;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC {ECO:0000269|PubMed:8650207}.
CC -!- INDUCTION: By proteasomal inhibitor PSI and prostaglandin J2 (PGJ2) (at
CC protein level). By phorbol 12-myristate 13-acetate (PMA). Expression is
CC directly activated by NFE2L2/NRF2; creating a positive feeback loop
CC (PubMed:20452972). {ECO:0000269|PubMed:12700667,
CC ECO:0000269|PubMed:15911346, ECO:0000269|PubMed:20452972,
CC ECO:0000269|PubMed:9762895}.
CC -!- DOMAIN: The UBA domain binds specifically 'Lys-63'-linked polyubiquitin
CC chains of polyubiquitinated substrates. Mediates the interaction with
CC TRIM55. Both the UBA and PB1 domains are necessary and sufficient for
CC the localization into the ubiquitin-containing inclusion bodies.
CC {ECO:0000269|PubMed:12857745, ECO:0000269|PubMed:15340068}.
CC -!- DOMAIN: The PB1 domain mediates homooligomerization and interactions
CC with FHOD3, MAP2K5, NBR1, PRKCI, PRKCZ and WDR81. Both the PB1 and UBA
CC domains are necessary and sufficient for the localization into the
CC ubiquitin-containing inclusion bodies. {ECO:0000269|PubMed:12813044,
CC ECO:0000269|PubMed:12887891, ECO:0000269|PubMed:15802564,
CC ECO:0000269|PubMed:28404643}.
CC -!- DOMAIN: The ZZ-type zinc finger mediates the interaction with RIPK1.
CC {ECO:0000269|PubMed:10747026}.
CC -!- DOMAIN: The LIR (LC3-interacting region) motif mediates the interaction
CC with ATG8 family proteins. {ECO:0000269|PubMed:23908376}.
CC -!- PTM: Phosphorylated. May be phosphorylated by PRKCZ (By similarity).
CC Phosphorylated in vitro by TTN (PubMed:15802564). Phosphorylation at
CC Ser-403 by ULK1 is stimulated by SESN2 (PubMed:25040165).
CC Phosphorylated at Ser-403 by TBK1, leading to promote relocalization of
CC 'Lys-63'-linked ubiquitinated STING1 to autophagosomes
CC (PubMed:29496741). Phosphorylation at Ser-349 by MTOR promotes
CC interaction with KEAP1 and inactivation of the BCR(KEAP1) complex,
CC promoting NFE2L2/NRF2 nuclear accumulation and expression of phase II
CC detoxifying enzymes (By similarity). {ECO:0000250|UniProtKB:Q64337,
CC ECO:0000269|PubMed:15802564, ECO:0000269|PubMed:25040165,
CC ECO:0000269|PubMed:29496741}.
CC -!- PTM: Ubiquitinated by UBE2J1 and RNF26 at Lys-435: ubiquitinated SQSTM1
CC attracts specific vesicle-associated adapters, forming a molecular
CC bridge that restrains cognate vesicles in the perinuclear region and
CC organizes the endosomal pathway for efficient cargo transport
CC (PubMed:27368102, PubMed:33472082). Deubiquitination by USP15 releases
CC target vesicles for fast transport into the cell periphery
CC (PubMed:27368102). Ubiquitinated by the BCR(KEAP1) complex at Lys-420,
CC increasing SQSTM1 sequestering activity and promoting its degradation
CC (PubMed:28380357). Ubiquitinated via 'Lys-29' and 'Lys-33'-linked
CC polyubiquitination leading to xenophagic targeting of bacteria and
CC inhibition of their replication (PubMed:27880896).
CC {ECO:0000269|PubMed:27368102, ECO:0000269|PubMed:27880896,
CC ECO:0000269|PubMed:28380357, ECO:0000269|PubMed:33472082}.
CC -!- DISEASE: Paget disease of bone 3 (PDB3) [MIM:167250]: A disorder of
CC bone remodeling characterized by increased bone turnover affecting one
CC or more sites throughout the skeleton, primarily the axial skeleton.
CC Osteoclastic overactivity followed by compensatory osteoblastic
CC activity leads to a structurally disorganized mosaic of bone (woven
CC bone), which is mechanically weaker, larger, less compact, more
CC vascular, and more susceptible to fracture than normal adult lamellar
CC bone. {ECO:0000269|PubMed:11992264, ECO:0000269|PubMed:12374763,
CC ECO:0000269|PubMed:14584883, ECO:0000269|PubMed:15125799,
CC ECO:0000269|PubMed:15146436, ECO:0000269|PubMed:15176995,
CC ECO:0000269|PubMed:15207768, ECO:0000269|PubMed:19931284}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Note=In a cell model for Huntington disease (HD), appears to
CC form a shell surrounding aggregates of mutant HTT that may protect
CC cells from apoptosis, possibly by recruiting autophagosomal components
CC to the polyubiquitinated protein aggregates.
CC {ECO:0000269|PubMed:16286508}.
CC -!- DISEASE: Frontotemporal dementia and/or amyotrophic lateral sclerosis 3
CC (FTDALS3) [MIM:616437]: A neurodegenerative disorder characterized by
CC frontotemporal dementia and/or amyotrophic lateral sclerosis in
CC affected individuals. There is high intrafamilial variation.
CC Frontotemporal dementia is characterized by frontal and temporal lobe
CC atrophy associated with neuronal loss, gliosis, and dementia. Patients
CC exhibit progressive changes in social, behavioral, and/or language
CC function. Amyotrophic lateral sclerosis is characterized by the death
CC of motor neurons in the brain, brainstem, and spinal cord, resulting in
CC fatal paralysis. Some FTDALS3 patients may also develop Paget disease
CC of bone. {ECO:0000269|PubMed:22084127, ECO:0000269|PubMed:24042580,
CC ECO:0000269|PubMed:24899140, ECO:0000269|PubMed:25114083}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Neurodegeneration with ataxia, dystonia, and gaze palsy,
CC childhood-onset (NADGP) [MIM:617145]: A neurodegenerative disorder
CC characterized by gait abnormalities, ataxia, dysarthria, dystonia,
CC vertical gaze palsy, and cognitive decline. Disease onset is in
CC childhood or adolescence. NADGP transmission pattern is consistent with
CC autosomal recessive inheritance. {ECO:0000269|PubMed:27545679}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- DISEASE: Myopathy, distal, with rimmed vacuoles (DMRV) [MIM:617158]: An
CC autosomal dominant myopathy with adult onset, characterized by muscle
CC weakness of the distal upper and lower limbs, walking difficulties, and
CC proximal weakness of the shoulder girdle muscles. Muscle biopsy shows
CC rimmed vacuoles. {ECO:0000269|PubMed:26208961}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- DISEASE: Note=A chromosomal aberration involving SQSTM1 is found in a
CC form of acute lymphoblastic leukemia. Translocation t(5;9)(q35;q34)
CC with NUP214. {ECO:0000269|PubMed:20851865}.
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; U41806; AAA93299.1; -; mRNA.
DR EMBL; U46751; AAC52070.1; -; mRNA.
DR EMBL; AK098077; BAG53577.1; -; mRNA.
DR EMBL; AK312451; BAG35358.1; -; mRNA.
DR EMBL; AC008393; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC000951; AAH00951.1; -; mRNA.
DR EMBL; BC001874; AAH01874.1; -; mRNA.
DR EMBL; BC003139; AAH03139.1; -; mRNA.
DR EMBL; BC017222; AAH17222.1; -; mRNA.
DR EMBL; BC019111; AAH19111.1; -; mRNA.
DR EMBL; AF060494; AAC64516.1; -; Genomic_DNA.
DR CCDS; CCDS34317.1; -. [Q13501-1]
DR CCDS; CCDS47355.1; -. [Q13501-2]
DR RefSeq; NP_001135770.1; NM_001142298.1. [Q13501-2]
DR RefSeq; NP_001135771.1; NM_001142299.1. [Q13501-2]
DR RefSeq; NP_003891.1; NM_003900.4. [Q13501-1]
DR RefSeq; XP_016865499.1; XM_017010010.1.
DR PDB; 1Q02; NMR; -; A=387-436.
DR PDB; 2JY7; NMR; -; A=387-436.
DR PDB; 2JY8; NMR; -; A=387-436.
DR PDB; 2K0B; NMR; -; X=387-436.
DR PDB; 2KNV; NMR; -; A/B=387-436.
DR PDB; 4MJS; X-ray; 2.50 A; B/D/F/H/J/L/N/P/R/T/V/X=3-102.
DR PDB; 4UF8; EM; 10.90 A; A/B/C/I=3-102.
DR PDB; 4UF9; EM; 10.30 A; A/B/D=1-122.
DR PDB; 5YP7; X-ray; 1.42 A; A/D=126-180.
DR PDB; 5YP8; X-ray; 1.45 A; A/B=126-180.
DR PDB; 5YPA; X-ray; 2.50 A; A/B=126-180.
DR PDB; 5YPB; X-ray; 2.90 A; A/B/C/D=126-180.
DR PDB; 5YPC; X-ray; 1.96 A; A/B/C/D=126-180.
DR PDB; 5YPE; X-ray; 2.85 A; A/B/C/D=126-180.
DR PDB; 5YPF; X-ray; 2.95 A; A/B/C/D=126-180.
DR PDB; 5YPG; X-ray; 2.20 A; A/B=126-180.
DR PDB; 5YPH; X-ray; 1.63 A; A/B=126-180.
DR PDB; 6JM4; X-ray; 3.20 A; A/B/C/D=1-102.
DR PDB; 6KHZ; X-ray; 2.80 A; A/B/C/D=125-169.
DR PDB; 6MJ7; X-ray; 1.41 A; A=120-171.
DR PDB; 6TGY; EM; 3.50 A; A=1-122.
DR PDB; 6TH3; EM; 4.00 A; A/B/C=1-122.
DR PDBsum; 1Q02; -.
DR PDBsum; 2JY7; -.
DR PDBsum; 2JY8; -.
DR PDBsum; 2K0B; -.
DR PDBsum; 2KNV; -.
DR PDBsum; 4MJS; -.
DR PDBsum; 4UF8; -.
DR PDBsum; 4UF9; -.
DR PDBsum; 5YP7; -.
DR PDBsum; 5YP8; -.
DR PDBsum; 5YPA; -.
DR PDBsum; 5YPB; -.
DR PDBsum; 5YPC; -.
DR PDBsum; 5YPE; -.
DR PDBsum; 5YPF; -.
DR PDBsum; 5YPG; -.
DR PDBsum; 5YPH; -.
DR PDBsum; 6JM4; -.
DR PDBsum; 6KHZ; -.
DR PDBsum; 6MJ7; -.
DR PDBsum; 6TGY; -.
DR PDBsum; 6TH3; -.
DR AlphaFoldDB; Q13501; -.
DR BMRB; Q13501; -.
DR SMR; Q13501; -.
DR BioGRID; 114397; 1027.
DR CORUM; Q13501; -.
DR DIP; DIP-34443N; -.
DR ELM; Q13501; -.
DR IntAct; Q13501; 212.
DR MINT; Q13501; -.
DR STRING; 9606.ENSP00000374455; -.
DR ChEMBL; CHEMBL4295816; -.
DR MoonDB; Q13501; Predicted.
DR GlyGen; Q13501; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q13501; -.
DR PhosphoSitePlus; Q13501; -.
DR SwissPalm; Q13501; -.
DR BioMuta; SQSTM1; -.
DR DMDM; 74735628; -.
DR EPD; Q13501; -.
DR jPOST; Q13501; -.
DR MassIVE; Q13501; -.
DR MaxQB; Q13501; -.
DR PaxDb; Q13501; -.
DR PeptideAtlas; Q13501; -.
DR PRIDE; Q13501; -.
DR ProteomicsDB; 59496; -. [Q13501-1]
DR ProteomicsDB; 59497; -. [Q13501-2]
DR Antibodypedia; 761; 1370 antibodies from 47 providers.
DR DNASU; 8878; -.
DR Ensembl; ENST00000360718.5; ENSP00000353944.5; ENSG00000161011.20. [Q13501-2]
DR Ensembl; ENST00000389805.9; ENSP00000374455.4; ENSG00000161011.20. [Q13501-1]
DR GeneID; 8878; -.
DR KEGG; hsa:8878; -.
DR MANE-Select; ENST00000389805.9; ENSP00000374455.4; NM_003900.5; NP_003891.1.
DR UCSC; uc003mkw.5; human. [Q13501-1]
DR CTD; 8878; -.
DR DisGeNET; 8878; -.
DR GeneCards; SQSTM1; -.
DR HGNC; HGNC:11280; SQSTM1.
DR HPA; ENSG00000161011; Tissue enhanced (skeletal).
DR MalaCards; SQSTM1; -.
DR MIM; 167250; phenotype.
DR MIM; 601530; gene.
DR MIM; 616437; phenotype.
DR MIM; 617145; phenotype.
DR MIM; 617158; phenotype.
DR neXtProt; NX_Q13501; -.
DR OpenTargets; ENSG00000161011; -.
DR Orphanet; 803; Amyotrophic lateral sclerosis.
DR Orphanet; 275864; Behavioral variant of frontotemporal dementia.
DR Orphanet; 603; Distal myopathy, Welander type.
DR Orphanet; 275872; Frontotemporal dementia with motor neuron disease.
DR Orphanet; 280110; NON RARE IN EUROPE: Paget disease of bone.
DR PharmGKB; PA36109; -.
DR VEuPathDB; HostDB:ENSG00000161011; -.
DR eggNOG; KOG4582; Eukaryota.
DR GeneTree; ENSGT00390000002781; -.
DR HOGENOM; CLU_038011_1_0_1; -.
DR InParanoid; Q13501; -.
DR OMA; IWHPLQW; -.
DR OrthoDB; 1275680at2759; -.
DR PhylomeDB; Q13501; -.
DR TreeFam; TF328470; -.
DR PathwayCommons; Q13501; -.
DR Reactome; R-HSA-205043; NRIF signals cell death from the nucleus.
DR Reactome; R-HSA-209543; p75NTR recruits signalling complexes.
DR Reactome; R-HSA-209560; NF-kB is activated and signals survival.
DR Reactome; R-HSA-5205685; PINK1-PRKN Mediated Mitophagy.
DR Reactome; R-HSA-8951664; Neddylation.
DR Reactome; R-HSA-9020702; Interleukin-1 signaling.
DR Reactome; R-HSA-9664873; Pexophagy.
DR Reactome; R-HSA-9725370; Signaling by ALK fusions and activated point mutants.
DR Reactome; R-HSA-9755511; KEAP1-NFE2L2 pathway.
DR Reactome; R-HSA-9759194; Nuclear events mediated by NFE2L2.
DR SignaLink; Q13501; -.
DR SIGNOR; Q13501; -.
DR BioGRID-ORCS; 8878; 25 hits in 1085 CRISPR screens.
DR ChiTaRS; SQSTM1; human.
DR EvolutionaryTrace; Q13501; -.
DR GeneWiki; Sequestosome_1; -.
DR GenomeRNAi; 8878; -.
DR Pharos; Q13501; Tbio.
DR PRO; PR:Q13501; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q13501; protein.
DR Bgee; ENSG00000161011; Expressed in right adrenal gland cortex and 175 other tissues.
DR ExpressionAtlas; Q13501; baseline and differential.
DR Genevisible; Q13501; HS.
DR GO; GO:0016235; C:aggresome; IBA:GO_Central.
DR GO; GO:0044753; C:amphisome; IDA:ParkinsonsUK-UCL.
DR GO; GO:0044754; C:autolysosome; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005776; C:autophagosome; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016234; C:inclusion body; IDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005770; C:late endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0097413; C:Lewy body; IEA:Ensembl.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0000932; C:P-body; IDA:UniProtKB.
DR GO; GO:0000407; C:phagophore assembly site; IEA:Ensembl.
DR GO; GO:0016605; C:PML body; IDA:UniProtKB.
DR GO; GO:0030017; C:sarcomere; IEA:UniProtKB-SubCell.
DR GO; GO:0097225; C:sperm midpiece; IEA:Ensembl.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0035255; F:ionotropic glutamate receptor binding; ISS:ARUK-UCL.
DR GO; GO:0070530; F:K63-linked polyubiquitin modification-dependent protein binding; IDA:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IDA:UniProtKB.
DR GO; GO:0005080; F:protein kinase C binding; IPI:UniProtKB.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; NAS:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; TAS:ProtInc.
DR GO; GO:0042169; F:SH2 domain binding; IDA:UniProtKB.
DR GO; GO:0043130; F:ubiquitin binding; IDA:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0035973; P:aggrephagy; IPI:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0006914; P:autophagy; IDA:UniProtKB.
DR GO; GO:0000422; P:autophagy of mitochondrion; NAS:ParkinsonsUK-UCL.
DR GO; GO:0070342; P:brown fat cell proliferation; IEA:Ensembl.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0016197; P:endosomal transport; TAS:UniProtKB.
DR GO; GO:0007032; P:endosome organization; IDA:UniProtKB.
DR GO; GO:0097009; P:energy homeostasis; IEA:Ensembl.
DR GO; GO:0002376; P:immune system process; IEA:UniProtKB-KW.
DR GO; GO:0035556; P:intracellular signal transduction; TAS:UniProtKB.
DR GO; GO:0016236; P:macroautophagy; IMP:GO_Central.
DR GO; GO:0000423; P:mitophagy; IGI:ParkinsonsUK-UCL.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0043065; P:positive regulation of apoptotic process; TAS:Reactome.
DR GO; GO:1900273; P:positive regulation of long-term synaptic potentiation; ISS:ARUK-UCL.
DR GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; ISS:ARUK-UCL.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; TAS:UniProtKB.
DR GO; GO:0006606; P:protein import into nucleus; IEA:Ensembl.
DR GO; GO:0008104; P:protein localization; TAS:UniProtKB.
DR GO; GO:1905719; P:protein localization to perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IEA:Ensembl.
DR GO; GO:0043122; P:regulation of I-kappaB kinase/NF-kappaB signaling; IMP:UniProtKB.
DR GO; GO:0010821; P:regulation of mitochondrion organization; NAS:ParkinsonsUK-UCL.
DR GO; GO:0061635; P:regulation of protein complex stability; IDA:UniProtKB.
DR GO; GO:0046578; P:regulation of Ras protein signal transduction; NAS:UniProtKB.
DR GO; GO:0002931; P:response to ischemia; IEA:Ensembl.
DR GO; GO:0098780; P:response to mitochondrial depolarisation; IGI:ParkinsonsUK-UCL.
DR GO; GO:0061912; P:selective autophagy; IMP:UniProtKB.
DR GO; GO:0001659; P:temperature homeostasis; IEA:Ensembl.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; TAS:ProtInc.
DR CDD; cd06402; PB1_p62; 1.
DR CDD; cd14320; UBA_SQSTM; 1.
DR DisProt; DP01111; -.
DR Gene3D; 3.30.60.90; -; 1.
DR IDEAL; IID00383; -.
DR InterPro; IPR000270; PB1_dom.
DR InterPro; IPR034866; PB1_p62.
DR InterPro; IPR033741; SQSTM_UBA.
DR InterPro; IPR015940; UBA.
DR InterPro; IPR009060; UBA-like_sf.
DR InterPro; IPR000433; Znf_ZZ.
DR InterPro; IPR043145; Znf_ZZ_sf.
DR Pfam; PF00564; PB1; 1.
DR Pfam; PF16577; UBA_5; 1.
DR Pfam; PF00569; ZZ; 1.
DR SMART; SM00666; PB1; 1.
DR SMART; SM00165; UBA; 1.
DR SMART; SM00291; ZnF_ZZ; 1.
DR SUPFAM; SSF46934; SSF46934; 1.
DR PROSITE; PS51745; PB1; 1.
DR PROSITE; PS50030; UBA; 1.
DR PROSITE; PS01357; ZF_ZZ_1; 1.
DR PROSITE; PS50135; ZF_ZZ_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing;
KW Amyotrophic lateral sclerosis; Apoptosis; Autophagy; Cytoplasm;
KW Cytoplasmic vesicle; Differentiation; Direct protein sequencing;
KW Disease variant; Endoplasmic reticulum; Endosome; Immunity;
KW Isopeptide bond; Lysosome; Metal-binding; Neurodegeneration; Nucleus;
KW Phosphoprotein; Reference proteome; Ubl conjugation; Zinc; Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22814378"
FT CHAIN 2..440
FT /note="Sequestosome-1"
FT /id="PRO_0000072176"
FT DOMAIN 3..102
FT /note="PB1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01081"
FT DOMAIN 389..434
FT /note="UBA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00212"
FT ZN_FING 123..173
FT /note="ZZ-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT REGION 2..50
FT /note="Interaction with LCK"
FT /evidence="ECO:0000269|PubMed:8650207"
FT REGION 43..107
FT /note="Interaction with PRKCZ and dimerization"
FT /evidence="ECO:0000250|UniProtKB:O08623"
FT REGION 50..80
FT /note="Interaction with PAWR"
FT /evidence="ECO:0000269|PubMed:11755531"
FT REGION 122..224
FT /note="Interaction with GABRR3"
FT /evidence="ECO:0000250|UniProtKB:O08623"
FT REGION 170..220
FT /note="LIM protein-binding (LB)"
FT REGION 196..235
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 264..390
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 269..440
FT /note="Interaction with NTRK1"
FT /evidence="ECO:0000250|UniProtKB:O08623"
FT REGION 321..342
FT /note="MAP1LC3B-binding"
FT /evidence="ECO:0000269|PubMed:17580304"
FT REGION 347..352
FT /note="Interaction with KEAP1"
FT /evidence="ECO:0000269|PubMed:20452972"
FT MOTIF 228..233
FT /note="TRAF6-binding"
FT MOTIF 336..341
FT /note="LIR"
FT COMPBIAS 269..306
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 314..328
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 344..372
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 128
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT BINDING 131
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT BINDING 142
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT BINDING 145
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT BINDING 151
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT BINDING 154
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT BINDING 160
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT BINDING 163
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT SITE 252..253
FT /note="Breakpoint for translocation to form the NUP214-
FT SQSTM1 fusion protein"
FT /evidence="ECO:0000269|PubMed:20851865"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 24
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 148
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:15592455"
FT MOD_RES 170
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 176
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 207
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 233
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 249
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 266
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 269
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 272
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 306
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 328
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 332
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 349
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q64337"
FT MOD_RES 355
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 361
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 365
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q64337"
FT MOD_RES 366
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 403
FT /note="Phosphoserine; by ULK1 and TBK1"
FT /evidence="ECO:0000269|PubMed:25040165,
FT ECO:0000269|PubMed:29496741"
FT CROSSLNK 91
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:27880896"
FT CROSSLNK 189
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:27880896"
FT CROSSLNK 420
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:28380357"
FT CROSSLNK 435
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000269|PubMed:33472082,
FT ECO:0007744|PubMed:28112733"
FT VAR_SEQ 1..84
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_015841"
FT VARIANT 16
FT /note="A -> V (in FTDALS3; dbSNP:rs1554162295)"
FT /evidence="ECO:0000269|PubMed:24899140"
FT /id="VAR_073899"
FT VARIANT 17
FT /note="A -> V (in dbSNP:rs141502868)"
FT /evidence="ECO:0000269|PubMed:24899140"
FT /id="VAR_073900"
FT VARIANT 33
FT /note="A -> V (in FTDALS3; dbSNP:rs200396166)"
FT /evidence="ECO:0000269|PubMed:22084127,
FT ECO:0000269|PubMed:24042580, ECO:0000269|PubMed:24899140"
FT /id="VAR_073901"
FT VARIANT 80
FT /note="D -> E (in FTDALS3; dbSNP:rs148366738)"
FT /evidence="ECO:0000269|PubMed:24899140"
FT /id="VAR_073902"
FT VARIANT 90
FT /note="V -> M (in FTDALS3; dbSNP:rs181263868)"
FT /evidence="ECO:0000269|PubMed:24899140"
FT /id="VAR_073903"
FT VARIANT 103
FT /note="K -> R (in dbSNP:rs748170760)"
FT /evidence="ECO:0000269|PubMed:24899140"
FT /id="VAR_073904"
FT VARIANT 107
FT /note="R -> Q"
FT /evidence="ECO:0000269|PubMed:24899140"
FT /id="VAR_073905"
FT VARIANT 107
FT /note="R -> W (in FTDALS3; dbSNP:rs771903158)"
FT /evidence="ECO:0000269|PubMed:24899140"
FT /id="VAR_073906"
FT VARIANT 108
FT /note="D -> Y"
FT /evidence="ECO:0000269|PubMed:24899140"
FT /id="VAR_073907"
FT VARIANT 110
FT /note="R -> H (in dbSNP:rs1267306593)"
FT /evidence="ECO:0000269|PubMed:24899140"
FT /id="VAR_073908"
FT VARIANT 117
FT /note="A -> V (in dbSNP:rs147810437)"
FT /evidence="ECO:0000269|PubMed:11992264,
FT ECO:0000269|PubMed:24899140"
FT /id="VAR_023590"
FT VARIANT 118
FT /note="P -> S (in dbSNP:rs200152247)"
FT /evidence="ECO:0000269|PubMed:24899140"
FT /id="VAR_073909"
FT VARIANT 119
FT /note="R -> G (in dbSNP:rs548787835)"
FT /evidence="ECO:0000269|PubMed:24899140"
FT /id="VAR_073910"
FT VARIANT 125
FT /note="N -> S (in dbSNP:rs769325755)"
FT /evidence="ECO:0000269|PubMed:24899140"
FT /id="VAR_073911"
FT VARIANT 129
FT /note="D -> N (in FTDALS3; dbSNP:rs753212399)"
FT /evidence="ECO:0000269|PubMed:24899140"
FT /id="VAR_073912"
FT VARIANT 139
FT /note="R -> C (in dbSNP:rs750256905)"
FT /evidence="ECO:0000269|PubMed:24899140"
FT /id="VAR_073913"
FT VARIANT 153
FT /note="V -> I (in FTDALS3; dbSNP:rs145056421)"
FT /evidence="ECO:0000269|PubMed:22084127,
FT ECO:0000269|PubMed:24899140"
FT /id="VAR_073914"
FT VARIANT 180
FT /note="S -> L (in dbSNP:rs1582008478)"
FT /evidence="ECO:0000269|PubMed:24899140"
FT /id="VAR_073915"
FT VARIANT 212
FT /note="R -> C (in FTDALS3; dbSNP:rs201263163)"
FT /evidence="ECO:0000269|PubMed:24899140"
FT /id="VAR_073916"
FT VARIANT 217
FT /note="R -> H (in dbSNP:rs761822261)"
FT /evidence="ECO:0000269|PubMed:24899140"
FT /id="VAR_073917"
FT VARIANT 219
FT /note="G -> V (in FTDALS3)"
FT /evidence="ECO:0000269|PubMed:24899140"
FT /id="VAR_073918"
FT VARIANT 226
FT /note="S -> P (in FTDALS3; dbSNP:rs765200636)"
FT /evidence="ECO:0000269|PubMed:24899140"
FT /id="VAR_073919"
FT VARIANT 228
FT /note="P -> L (in FTDALS3; dbSNP:rs151191977)"
FT /evidence="ECO:0000269|PubMed:22084127,
FT ECO:0000269|PubMed:24899140"
FT /id="VAR_073920"
FT VARIANT 232
FT /note="P -> T (in FTDALS3; dbSNP:rs1225746517)"
FT /evidence="ECO:0000269|PubMed:24899140"
FT /id="VAR_073921"
FT VARIANT 238
FT /note="K -> E (confirmed at protein level;
FT dbSNP:rs11548633)"
FT /evidence="ECO:0000269|PubMed:17488105,
FT ECO:0000269|PubMed:24899140"
FT /id="VAR_068915"
FT VARIANT 238
FT /note="Missing (in FTDALS3)"
FT /evidence="ECO:0000269|PubMed:22084127,
FT ECO:0000269|PubMed:24899140, ECO:0000269|PubMed:25114083"
FT /id="VAR_073922"
FT VARIANT 258
FT /note="D -> N (in FTDALS3; dbSNP:rs774986849)"
FT /evidence="ECO:0000269|PubMed:24899140"
FT /id="VAR_073923"
FT VARIANT 265..266
FT /note="RS -> SR"
FT /evidence="ECO:0000269|PubMed:24899140"
FT /id="VAR_073924"
FT VARIANT 274
FT /note="E -> D (in dbSNP:rs55793208)"
FT /evidence="ECO:0000269|PubMed:24899140"
FT /id="VAR_061707"
FT VARIANT 274
FT /note="E -> Q"
FT /evidence="ECO:0000269|PubMed:11992264"
FT /id="VAR_023591"
FT VARIANT 278
FT /note="T -> I (in dbSNP:rs200445838)"
FT /evidence="ECO:0000269|PubMed:24899140"
FT /id="VAR_073925"
FT VARIANT 308
FT /note="A -> V (in dbSNP:rs541356917)"
FT /evidence="ECO:0000269|PubMed:24899140"
FT /id="VAR_073926"
FT VARIANT 318
FT /note="S -> P (in FTDALS3)"
FT /evidence="ECO:0000269|PubMed:22084127"
FT /id="VAR_073927"
FT VARIANT 319
FT /note="E -> K (in dbSNP:rs61748794)"
FT /evidence="ECO:0000269|PubMed:24899140"
FT /id="VAR_073928"
FT VARIANT 321
FT /note="R -> C (in FTDALS3; likely benign variant;
FT dbSNP:rs140226523)"
FT /evidence="ECO:0000269|PubMed:22084127,
FT ECO:0000269|PubMed:24899140"
FT /id="VAR_073929"
FT VARIANT 329
FT /note="D -> G (in FTDALS3; dbSNP:rs148294622)"
FT /evidence="ECO:0000269|PubMed:24899140"
FT /id="VAR_073930"
FT VARIANT 334
FT /note="Missing"
FT /evidence="ECO:0000269|PubMed:24899140"
FT /id="VAR_073931"
FT VARIANT 348
FT /note="P -> L (in FTDALS3; dbSNP:rs772889843)"
FT /evidence="ECO:0000269|PubMed:24899140"
FT /id="VAR_073932"
FT VARIANT 349
FT /note="S -> T (in dbSNP:rs774512680)"
FT /evidence="ECO:0000269|PubMed:24899140"
FT /id="VAR_073933"
FT VARIANT 370
FT /note="S -> P (in FTDALS3; dbSNP:rs143956614)"
FT /evidence="ECO:0000269|PubMed:22084127"
FT /id="VAR_073934"
FT VARIANT 381
FT /note="A -> V (in FTDALS3; dbSNP:rs772122047)"
FT /evidence="ECO:0000269|PubMed:24042580"
FT /id="VAR_073935"
FT VARIANT 387
FT /note="P -> L (in PDB3 and FTDALS3; dbSNP:rs776749939)"
FT /evidence="ECO:0000269|PubMed:14584883,
FT ECO:0000269|PubMed:24042580, ECO:0000269|PubMed:24899140"
FT /id="VAR_023592"
FT VARIANT 392
FT /note="P -> L (in PDB3 and FTDALS3; no effect on
FT polyubiquitin-binding; dbSNP:rs104893941)"
FT /evidence="ECO:0000269|PubMed:11992264,
FT ECO:0000269|PubMed:12374763, ECO:0000269|PubMed:12857745,
FT ECO:0000269|PubMed:15125799, ECO:0000269|PubMed:15146436,
FT ECO:0000269|PubMed:15207768, ECO:0000269|PubMed:22084127,
FT ECO:0000269|PubMed:24042580, ECO:0000269|PubMed:24899140"
FT /id="VAR_023593"
FT VARIANT 399
FT /note="S -> P (in PDB3; dbSNP:rs1561609625)"
FT /evidence="ECO:0000269|PubMed:15146436"
FT /id="VAR_023594"
FT VARIANT 404
FT /note="M -> T (in PDB3; dbSNP:rs1247551175)"
FT /evidence="ECO:0000269|PubMed:15146436"
FT /id="VAR_023595"
FT VARIANT 404
FT /note="M -> V (in PDB3; loss of polyubiquitin-binding;
FT dbSNP:rs771966860)"
FT /evidence="ECO:0000269|PubMed:15125799,
FT ECO:0000269|PubMed:15176995"
FT /id="VAR_023596"
FT VARIANT 411
FT /note="G -> S (in PDB3 and FTDALS3; no effect on
FT polyubiquitin-binding; dbSNP:rs143511494)"
FT /evidence="ECO:0000269|PubMed:15176995,
FT ECO:0000269|PubMed:22084127"
FT /id="VAR_023597"
FT VARIANT 425
FT /note="G -> R (in PDB3 and FTDALS3; loss of polyubiquitin-
FT binding and increased activation of NF-kappa-B;
FT dbSNP:rs757212984)"
FT /evidence="ECO:0000269|PubMed:15125799,
FT ECO:0000269|PubMed:15146436, ECO:0000269|PubMed:15176995,
FT ECO:0000269|PubMed:19931284, ECO:0000269|PubMed:22084127"
FT /id="VAR_023598"
FT VARIANT 430
FT /note="T -> P (in FTDALS3; dbSNP:rs770118706)"
FT /evidence="ECO:0000269|PubMed:24899140"
FT /id="VAR_073936"
FT VARIANT 439
FT /note="P -> L (in dbSNP:rs199854262)"
FT /evidence="ECO:0000269|PubMed:24899140"
FT /id="VAR_073937"
FT MUTAGEN 7
FT /note="K->A: Loss of interactions with PRKCZ, PRCKI and
FT NBR1. Loss of dimerization; when associated with A-69."
FT /evidence="ECO:0000269|PubMed:12813044,
FT ECO:0000269|PubMed:12887891"
FT MUTAGEN 9
FT /note="Y->F: No effect on interaction with LCK."
FT /evidence="ECO:0000269|PubMed:8650207"
FT MUTAGEN 13
FT /note="K->A: No effect on interaction with PRKCI."
FT /evidence="ECO:0000269|PubMed:12813044"
FT MUTAGEN 21..22
FT /note="RR->AA: Loss of interaction with PRKCI. Alters
FT dimerization."
FT /evidence="ECO:0000269|PubMed:12813044"
FT MUTAGEN 67
FT /note="Y->A: No effect on interaction with PRKCZ."
FT /evidence="ECO:0000269|PubMed:12813044"
FT MUTAGEN 69
FT /note="D->A: No effect on interactions with PRKCZ, PRKCI
FT and NBR1. Loss of localization in cytoplasmic inclusion
FT bodies. Loss of dimerization; when associated with A-7."
FT /evidence="ECO:0000269|PubMed:12813044,
FT ECO:0000269|PubMed:12887891, ECO:0000269|PubMed:16286508"
FT MUTAGEN 71
FT /note="D->A: No effect on interaction with PRKCI."
FT /evidence="ECO:0000269|PubMed:12813044"
FT MUTAGEN 73
FT /note="D->A: No effect on interactions with PRKCZ and
FT PRKCI."
FT /evidence="ECO:0000269|PubMed:12813044,
FT ECO:0000269|PubMed:12887891"
FT MUTAGEN 80
FT /note="D->A: No effect on interaction with PRKCI."
FT /evidence="ECO:0000269|PubMed:12813044"
FT MUTAGEN 82
FT /note="E->A: No effect on interaction with PRKCI."
FT /evidence="ECO:0000269|PubMed:12813044"
FT MUTAGEN 323..324
FT /note="EE->AA: No effect on MAP1LC3B-binding."
FT /evidence="ECO:0000269|PubMed:17580304"
FT MUTAGEN 332
FT /note="S->A: No effect on MAP1LC3B-binding."
FT /evidence="ECO:0000269|PubMed:17580304"
FT MUTAGEN 335..337
FT /note="DDD->ADA: 75% decrease in MAP1LC3B-binding."
FT /evidence="ECO:0000269|PubMed:17580304"
FT MUTAGEN 338
FT /note="W->A: Strong decrease in MAP1LC3B-binding, disrupts
FT interaction with GABARAP."
FT /evidence="ECO:0000269|PubMed:17580304,
FT ECO:0000269|PubMed:24668264"
FT MUTAGEN 342
FT /note="S->A: No effect on MAP1LC3B-binding."
FT /evidence="ECO:0000269|PubMed:17580304"
FT MUTAGEN 347
FT /note="D->A: Strongly decreased interaction with KEAP1."
FT /evidence="ECO:0000269|PubMed:20452972"
FT MUTAGEN 350
FT /note="T->A: Strongly decreased interaction with KEAP1."
FT /evidence="ECO:0000269|PubMed:20452972"
FT MUTAGEN 351
FT /note="G->A: Strongly decreased interaction with KEAP1."
FT /evidence="ECO:0000269|PubMed:20452972"
FT MUTAGEN 352
FT /note="E->A: Strongly decreased interaction with KEAP1."
FT /evidence="ECO:0000269|PubMed:20452972"
FT MUTAGEN 398
FT /note="L->V: No effect on polyubiquitin-binding."
FT /evidence="ECO:0000269|PubMed:15340068"
FT MUTAGEN 403
FT /note="S->A: Abolished ability to promote relocalization of
FT 'Lys-63'-linked ubiquitinated STING1 to autophagosomes."
FT /evidence="ECO:0000269|PubMed:29496741"
FT MUTAGEN 406
FT /note="F->V: Loss of polyubiquitin-binding."
FT /evidence="ECO:0000269|PubMed:15340068"
FT MUTAGEN 409
FT /note="E->K: Decreased activation of NF-kappa-B."
FT /evidence="ECO:0000269|PubMed:19931284"
FT MUTAGEN 410
FT /note="G->K: Decreased activation of NF-kappa-B."
FT /evidence="ECO:0000269|PubMed:19931284"
FT MUTAGEN 413
FT /note="L->V: No effect on polyubiquitin-binding."
FT /evidence="ECO:0000269|PubMed:15340068"
FT MUTAGEN 417
FT /note="L->V: Loss of polyubiquitin-binding."
FT /evidence="ECO:0000269|PubMed:15340068"
FT MUTAGEN 420
FT /note="K->R: Decreased ubiquitination by the BCR(KEAP1)
FT complex, leading to decreased sequestering activity."
FT /evidence="ECO:0000269|PubMed:28380357"
FT MUTAGEN 431
FT /note="I->V: Partial loss of polyubiquitin-binding. Loss of
FT localization to cytoplasmic inclusion bodies."
FT /evidence="ECO:0000269|PubMed:15340068,
FT ECO:0000269|PubMed:16286508"
FT CONFLICT 321
FT /note="R -> A (in Ref. 1; AAA93299)"
FT /evidence="ECO:0000305"
FT STRAND 5..10
FT /evidence="ECO:0007829|PDB:4MJS"
FT STRAND 13..15
FT /evidence="ECO:0007829|PDB:6TGY"
FT STRAND 19..24
FT /evidence="ECO:0007829|PDB:4MJS"
FT STRAND 36..39
FT /evidence="ECO:0007829|PDB:6TGY"
FT HELIX 43..54
FT /evidence="ECO:0007829|PDB:4MJS"
FT STRAND 62..64
FT /evidence="ECO:0007829|PDB:4MJS"
FT STRAND 66..68
FT /evidence="ECO:0007829|PDB:4MJS"
FT STRAND 74..76
FT /evidence="ECO:0007829|PDB:4MJS"
FT HELIX 80..88
FT /evidence="ECO:0007829|PDB:4MJS"
FT STRAND 92..101
FT /evidence="ECO:0007829|PDB:4MJS"
FT STRAND 120..122
FT /evidence="ECO:0007829|PDB:6MJ7"
FT TURN 129..131
FT /evidence="ECO:0007829|PDB:6MJ7"
FT STRAND 132..134
FT /evidence="ECO:0007829|PDB:6KHZ"
FT STRAND 139..147
FT /evidence="ECO:0007829|PDB:6MJ7"
FT HELIX 152..156
FT /evidence="ECO:0007829|PDB:6MJ7"
FT TURN 157..162
FT /evidence="ECO:0007829|PDB:6MJ7"
FT STRAND 165..168
FT /evidence="ECO:0007829|PDB:6MJ7"
FT STRAND 388..390
FT /evidence="ECO:0007829|PDB:2JY7"
FT HELIX 392..402
FT /evidence="ECO:0007829|PDB:1Q02"
FT TURN 403..405
FT /evidence="ECO:0007829|PDB:2JY7"
FT STRAND 409..411
FT /evidence="ECO:0007829|PDB:2JY7"
FT HELIX 412..419
FT /evidence="ECO:0007829|PDB:1Q02"
FT TURN 420..422
FT /evidence="ECO:0007829|PDB:1Q02"
FT HELIX 424..431
FT /evidence="ECO:0007829|PDB:1Q02"
FT STRAND 432..434
FT /evidence="ECO:0007829|PDB:2JY8"
FT INIT_MET Q13501-2:1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES Q13501-2:2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:22814378"
SQ SEQUENCE 440 AA; 47687 MW; 462D94C171F337CD CRC64;
MASLTVKAYL LGKEDAAREI RRFSFCCSPE PEAEAEAAAG PGPCERLLSR VAALFPALRP
GGFQAHYRDE DGDLVAFSSD EELTMAMSYV KDDIFRIYIK EKKECRRDHR PPCAQEAPRN
MVHPNVICDG CNGPVVGTRY KCSVCPDYDL CSVCEGKGLH RGHTKLAFPS PFGHLSEGFS
HSRWLRKVKH GHFGWPGWEM GPPGNWSPRP PRAGEARPGP TAESASGPSE DPSVNFLKNV
GESVAAALSP LGIEVDIDVE HGGKRSRLTP VSPESSSTEE KSSSQPSSCC SDPSKPGGNV
EGATQSLAEQ MRKIALESEG RPEEQMESDN CSGGDDDWTH LSSKEVDPST GELQSLQMPE
SEGPSSLDPS QEGPTGLKEA ALYPHLPPEA DPRLIESLSQ MLSMGFSDEG GWLTRLLQTK
NYDIGAALDT IQYSKHPPPL
