Full text data of ATG4B
ATG4B
(APG4B, AUTL1, KIAA0943)
[Confidence: low (only semi-automatic identification from reviews)]
Cysteine protease ATG4B; 3.4.22.- (AUT-like 1 cysteine endopeptidase; Autophagin-1; Autophagy-related cysteine endopeptidase 1; Autophagy-related protein 4 homolog B; hAPG4B)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Cysteine protease ATG4B; 3.4.22.- (AUT-like 1 cysteine endopeptidase; Autophagin-1; Autophagy-related cysteine endopeptidase 1; Autophagy-related protein 4 homolog B; hAPG4B)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q9Y4P1
ID ATG4B_HUMAN Reviewed; 393 AA.
AC Q9Y4P1; B7WNK2; Q53NU4; Q6ZUV8; Q8WYM9; Q96K07; Q96K96; Q96SZ1;
read moreAC Q9Y2F2;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 22-JAN-2014, entry version 123.
DE RecName: Full=Cysteine protease ATG4B;
DE EC=3.4.22.-;
DE AltName: Full=AUT-like 1 cysteine endopeptidase;
DE AltName: Full=Autophagin-1;
DE AltName: Full=Autophagy-related cysteine endopeptidase 1;
DE AltName: Full=Autophagy-related protein 4 homolog B;
DE Short=hAPG4B;
GN Name=ATG4B; Synonyms=APG4B, AUTL1, KIAA0943;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND
RP VARIANT GLN-354.
RC TISSUE=Liver;
RX PubMed=12446702; DOI=10.1074/jbc.M208247200;
RA Marino G., Uria J.A., Puente X.S., Quesada V., Bordallo J.,
RA Lopez-Otin C.;
RT "Human autophagins, a family of cysteine proteinases potentially
RT implicated in cell degradation by autophagy.";
RL J. Biol. Chem. 278:3671-3678(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, FUNCTION
RP IN GABARAPL2; GABARAP AND MAP1LC3A CLEAVAGE, MUTAGENESIS OF CYS-74,
RP AND VARIANT GLN-354.
RX PubMed=15169837; DOI=10.1242/jcs.01131;
RA Kabeya Y., Mizushima N., Yamamoto A., Oshitani-Okamoto S., Ohsumi Y.,
RA Yoshimori T.;
RT "LC3, GABARAP and GATE16 localize to autophagosomal membrane depending
RT on form-II formation.";
RL J. Cell Sci. 117:2805-2812(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
RP GLN-354.
RC TISSUE=Brain;
RX PubMed=10231032; DOI=10.1093/dnares/6.1.63;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M.,
RA Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIII.
RT The complete sequences of 100 new cDNA clones from brain which code
RT for large proteins in vitro.";
RL DNA Res. 6:63-70(1999).
RN [4]
RP SEQUENCE REVISION.
RA Ohara O., Nagase T., Kikuno R.;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 3; 4 AND 6).
RC TISSUE=Embryo, and Placenta;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
RP GLN-354.
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
RP GLN-354.
RC TISSUE=Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP PROTEIN SEQUENCE OF 1-12; 33-49; 120-137; 185-201 AND 230-244,
RP ACETYLATION AT MET-1, AND MASS SPECTROMETRY.
RC TISSUE=Ovarian carcinoma;
RA Bienvenut W.V.;
RL Submitted (JAN-2010) to UniProtKB.
RN [10]
RP FUNCTION, AND MUTAGENESIS OF CYS-74.
RX PubMed=15187094; DOI=10.1074/jbc.M401461200;
RA Tanida I., Sou Y.-S., Ezaki J., Minematsu-Ikeguchi N., Ueno T.,
RA Kominami E.;
RT "HsAtg4B/HsApg4B/autophagin-1 cleaves the carboxyl termini of three
RT human Atg8 homologues and delipidates microtubule-associated protein
RT light chain 3- and GABAA receptor-associated protein-phospholipid
RT conjugates.";
RL J. Biol. Chem. 279:36268-36276(2004).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-383, AND MASS
RP SPECTROMETRY.
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.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [12]
RP FUNCTION, ENZYME REGULATION, AND MUTAGENESIS OF CYS-78.
RX PubMed=17347651; DOI=10.1038/sj.emboj.7601623;
RA Scherz-Shouval R., Shvets E., Fass E., Shorer H., Gil L., Elazar Z.;
RT "Reactive oxygen species are essential for autophagy and specifically
RT regulate the activity of Atg4.";
RL EMBO J. 26:1749-1760(2007).
RN [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-383, AND MASS
RP SPECTROMETRY.
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 [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-383, AND MASS
RP SPECTROMETRY.
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 [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-383, AND MASS
RP SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [18]
RP FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=21177865; DOI=10.1074/jbc.M110.199059;
RA Li M., Hou Y., Wang J., Chen X., Shao Z.M., Yin X.M.;
RT "Kinetics comparisons of mammalian Atg4 homologues indicate selective
RT preferences toward diverse Atg8 substrates.";
RL J. Biol. Chem. 286:7327-7338(2011).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-383, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [20]
RP FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=22302004; DOI=10.4161/auto.18777;
RA Li M., Chen X., Ye Q.Z., Vogt A., Yin X.M.;
RT "A high-throughput FRET-based assay for determination of Atg4
RT activity.";
RL Autophagy 8:401-412(2012).
RN [21]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS), AND MUTAGENESIS OF CYS-74;
RP TRP-142; ARG-229; ASP-278 AND HIS-280.
RX PubMed=16183633; DOI=10.1074/jbc.M509158200;
RA Sugawara K., Suzuki N.N., Fujioka Y., Mizushima N., Ohsumi Y.,
RA Inagaki F.;
RT "Structural basis for the specificity and catalysis of human Atg4B
RT responsible for mammalian autophagy.";
RL J. Biol. Chem. 280:40058-40065(2005).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS), AND MUTAGENESIS OF CYS-74;
RP ASP-278 AND HIS-280.
RX PubMed=16325851; DOI=10.1016/j.jmb.2005.11.018;
RA Kumanomidou T., Mizushima T., Komatsu M., Suzuki A., Tanida I.,
RA Sou Y.-S., Ueno T., Kominami E., Tanaka K., Yamane T.;
RT "The crystal structure of human Atg4b, a processing and de-conjugating
RT enzyme for autophagosome-forming modifiers.";
RL J. Mol. Biol. 355:612-618(2006).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 1-353 IN COMPLEX WITH RAT
RP MAP1LC3B/LC3, AND FUNCTION.
RX PubMed=19322194; DOI=10.1038/emboj.2009.80;
RA Satoo K., Noda N.N., Kumeta H., Fujioka Y., Mizushima N., Ohsumi Y.,
RA Inagaki F.;
RT "The structure of Atg4B-LC3 complex reveals the mechanism of LC3
RT processing and delipidation during autophagy.";
RL EMBO J. 28:1341-1350(2009).
CC -!- FUNCTION: Cysteine protease required for the cytoplasm to vacuole
CC transport (Cvt) and autophagy. Cleaves the C-terminal amino acid
CC of ATG8 family proteins MAP1LC3, GABARAPL1, GABARAPL2 and GABARAP,
CC to reveal a C-terminal glycine. Exposure of the glycine at the C-
CC terminus is essential for ATG8 proteins conjugation to
CC phosphatidylethanolamine (PE) and insertion to membranes, which is
CC necessary for autophagy. Has also an activity of delipidating
CC enzyme for the PE-conjugated forms.
CC -!- ENZYME REGULATION: Inhibited by N-ethylmaleimide. Redox-regulated
CC during autophagy since reducing conditions activate ATG4A whereas
CC an oxidizing environment such as the presence of H(2)O(2) inhibits
CC its activity.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=5.1 uM for MAP1LC3B;
CC KM=5.8 uM for GABARAP;
CC KM=4.4 uM for GABARAPL1;
CC KM=6.1 uM for GABARAPL2;
CC -!- INTERACTION:
CC O95166:GABARAP; NbExp=8; IntAct=EBI-712014, EBI-712001;
CC Q9H0R8:GABARAPL1; NbExp=7; IntAct=EBI-712014, EBI-746969;
CC P60520:GABARAPL2; NbExp=7; IntAct=EBI-712014, EBI-720116;
CC Q9GZQ8:MAP1LC3B; NbExp=11; IntAct=EBI-712014, EBI-373144;
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q9Y4P1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y4P1-2; Sequence=VSP_013029, VSP_013034;
CC Note=No experimental confirmation available;
CC Name=3;
CC IsoId=Q9Y4P1-3; Sequence=VSP_013028, VSP_013031, VSP_013032;
CC Note=No experimental confirmation available;
CC Name=4;
CC IsoId=Q9Y4P1-4; Sequence=VSP_013028, VSP_013033;
CC Name=6;
CC IsoId=Q9Y4P1-6; Sequence=VSP_013034;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Mainly expressed in the skeletal muscle,
CC followed by brain, heart, liver and pancreas.
CC -!- SIMILARITY: Belongs to the peptidase C54 family.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA76787.2; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC Sequence=BAC86110.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
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DR EMBL; AJ504652; CAD43219.1; -; mRNA.
DR EMBL; AB066215; BAB83890.1; -; mRNA.
DR EMBL; AB023160; BAA76787.2; ALT_INIT; mRNA.
DR EMBL; AK027332; BAB55042.1; -; mRNA.
DR EMBL; AK027462; BAB55127.1; -; mRNA.
DR EMBL; AK027763; BAB55353.1; -; mRNA.
DR EMBL; AK125277; BAC86110.1; ALT_INIT; mRNA.
DR EMBL; AL080168; CAB45756.1; -; mRNA.
DR EMBL; AC133528; AAY14919.1; -; Genomic_DNA.
DR EMBL; BC000719; AAH00719.1; -; mRNA.
DR PIR; T12492; T12492.
DR RefSeq; NP_037457.3; NM_013325.4.
DR RefSeq; NP_847896.1; NM_178326.2.
DR UniGene; Hs.283610; -.
DR PDB; 2CY7; X-ray; 1.90 A; A=1-393.
DR PDB; 2D1I; X-ray; 2.00 A; A/B=1-393.
DR PDB; 2Z0D; X-ray; 1.90 A; A=1-353.
DR PDB; 2Z0E; X-ray; 1.90 A; A=1-353.
DR PDB; 2ZZP; X-ray; 2.05 A; A=1-353.
DR PDBsum; 2CY7; -.
DR PDBsum; 2D1I; -.
DR PDBsum; 2Z0D; -.
DR PDBsum; 2Z0E; -.
DR PDBsum; 2ZZP; -.
DR ProteinModelPortal; Q9Y4P1; -.
DR SMR; Q9Y4P1; 10-373.
DR IntAct; Q9Y4P1; 18.
DR MINT; MINT-1414043; -.
DR STRING; 9606.ENSP00000384259; -.
DR BindingDB; Q9Y4P1; -.
DR ChEMBL; CHEMBL1741221; -.
DR MEROPS; C54.003; -.
DR PhosphoSite; Q9Y4P1; -.
DR DMDM; 296434400; -.
DR PaxDb; Q9Y4P1; -.
DR PRIDE; Q9Y4P1; -.
DR DNASU; 23192; -.
DR Ensembl; ENST00000402096; ENSP00000384661; ENSG00000168397.
DR Ensembl; ENST00000404914; ENSP00000384259; ENSG00000168397.
DR Ensembl; ENST00000405546; ENSP00000383964; ENSG00000168397.
DR GeneID; 23192; -.
DR KEGG; hsa:23192; -.
DR UCSC; uc002wbv.3; human.
DR CTD; 23192; -.
DR GeneCards; GC02P242578; -.
DR H-InvDB; HIX0180188; -.
DR HGNC; HGNC:20790; ATG4B.
DR HPA; CAB037195; -.
DR MIM; 611338; gene.
DR neXtProt; NX_Q9Y4P1; -.
DR PharmGKB; PA134898340; -.
DR eggNOG; NOG239662; -.
DR HOVERGEN; HBG050536; -.
DR KO; K08342; -.
DR OMA; RNFPAIG; -.
DR OrthoDB; EOG73V6KD; -.
DR ChiTaRS; ATG4B; human.
DR EvolutionaryTrace; Q9Y4P1; -.
DR GeneWiki; ATG4B; -.
DR GenomeRNAi; 23192; -.
DR NextBio; 44679; -.
DR PRO; PR:Q9Y4P1; -.
DR ArrayExpress; Q9Y4P1; -.
DR Bgee; Q9Y4P1; -.
DR CleanEx; HS_ATG4B; -.
DR Genevestigator; Q9Y4P1; -.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0008234; F:cysteine-type peptidase activity; IDA:UniProtKB.
DR GO; GO:0004175; F:endopeptidase activity; IDA:BHF-UCL.
DR GO; GO:0000045; P:autophagic vacuole assembly; IGI:UniProtKB.
DR GO; GO:0010508; P:positive regulation of autophagy; IDA:BHF-UCL.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
DR InterPro; IPR005078; Peptidase_C54.
DR PANTHER; PTHR22624; PTHR22624; 1.
DR Pfam; PF03416; Peptidase_C54; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Autophagy;
KW Complete proteome; Cytoplasm; Direct protein sequencing; Hydrolase;
KW Phosphoprotein; Polymorphism; Protease; Protein transport;
KW Reference proteome; Thiol protease; Transport;
KW Ubl conjugation pathway.
FT CHAIN 1 393 Cysteine protease ATG4B.
FT /FTId=PRO_0000215844.
FT ACT_SITE 74 74 Nucleophile.
FT ACT_SITE 278 278 Potential.
FT ACT_SITE 280 280
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 383 383 Phosphoserine.
FT VAR_SEQ 1 74 Missing (in isoform 3 and isoform 4).
FT /FTId=VSP_013028.
FT VAR_SEQ 1 1 M -> MAHSVPSDSRTSRRPTTRPHAARGAPRGSRRPGRTP
FT KWRLPRISARAPYRLRRLRRHTYWPPRRPVAASRCWPVGAT
FT PLGSVGGRTGKM (in isoform 2).
FT /FTId=VSP_013029.
FT VAR_SEQ 321 354 FFCKTEDDFNDWCQQVKKLSLLGGALPMFELVEL -> KQG
FT RLVRSLIPWAPRPSSWCAAVLGAAVVMCGTP (in
FT isoform 3).
FT /FTId=VSP_013031.
FT VAR_SEQ 355 393 Missing (in isoform 3).
FT /FTId=VSP_013032.
FT VAR_SEQ 369 369 L -> LGESCQVQVGSLG (in isoform 4).
FT /FTId=VSP_013033.
FT VAR_SEQ 370 393 DSSDVERLERFFDSEDEDFEILSL -> GESCQVQILLM
FT (in isoform 2 and isoform 6).
FT /FTId=VSP_013034.
FT VARIANT 354 354 L -> Q (in dbSNP:rs7601000).
FT /FTId=VAR_021486.
FT MUTAGEN 74 74 C->S: Complete loss of protease activity.
FT MUTAGEN 78 78 C->A: Reduces the redox sensitivity and
FT retains activity in presence of H(2)O(2).
FT MUTAGEN 142 142 W->A: Strongly reduced protease activity.
FT MUTAGEN 229 229 R->A: Strongly reduced protease activity.
FT MUTAGEN 278 278 D->A: Complete loss of protease activity.
FT MUTAGEN 280 280 H->A: Complete loss of protease activity.
FT CONFLICT 136 136 Missing (in Ref. 2; BAB83890).
FT CONFLICT 188 188 P -> L (in Ref. 5; BAB55127).
FT CONFLICT 247 247 F -> Y (in Ref. 5; BAB55353).
FT CONFLICT 273 273 E -> G (in Ref. 5; BAB55042).
FT CONFLICT 312 312 E -> N (in Ref. 2; BAB83890).
FT HELIX 5 7
FT HELIX 10 13
FT HELIX 14 18
FT STRAND 22 24
FT STRAND 26 28
FT STRAND 31 33
FT TURN 35 37
FT HELIX 39 48
FT STRAND 54 57
FT TURN 61 64
FT TURN 70 72
FT HELIX 74 91
FT STRAND 100 102
FT HELIX 106 113
FT STRAND 116 118
FT HELIX 125 133
FT TURN 134 136
FT HELIX 145 156
FT TURN 160 162
FT STRAND 165 168
FT STRAND 173 175
FT HELIX 176 183
FT STRAND 184 186
FT STRAND 222 229
FT STRAND 232 234
FT HELIX 237 239
FT HELIX 240 246
FT STRAND 252 257
FT STRAND 264 270
FT STRAND 273 277
FT STRAND 281 284
FT STRAND 290 292
FT HELIX 297 299
FT STRAND 306 309
FT HELIX 310 312
FT STRAND 315 325
FT HELIX 326 341
FT STRAND 349 353
FT HELIX 371 376
SQ SEQUENCE 393 AA; 44294 MW; F4ADB3192176E0E5 CRC64;
MDAATLTYDT LRFAEFEDFP ETSEPVWILG RKYSIFTEKD EILSDVASRL WFTYRKNFPA
IGGTGPTSDT GWGCMLRCGQ MIFAQALVCR HLGRDWRWTQ RKRQPDSYFS VLNAFIDRKD
SYYSIHQIAQ MGVGEGKSIG QWYGPNTVAQ VLKKLAVFDT WSSLAVHIAM DNTVVMEEIR
RLCRTSVPCA GATAFPADSD RHCNGFPAGA EVTNRPSPWR PLVLLIPLRL GLTDINEAYV
ETLKHCFMMP QSLGVIGGKP NSAHYFIGYV GEELIYLDPH TTQPAVEPTD GCFIPDESFH
CQHPPCRMSI AELDPSIAVG FFCKTEDDFN DWCQQVKKLS LLGGALPMFE LVELQPSHLA
CPDVLNLSLD SSDVERLERF FDSEDEDFEI LSL
//
ID ATG4B_HUMAN Reviewed; 393 AA.
AC Q9Y4P1; B7WNK2; Q53NU4; Q6ZUV8; Q8WYM9; Q96K07; Q96K96; Q96SZ1;
read moreAC Q9Y2F2;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 22-JAN-2014, entry version 123.
DE RecName: Full=Cysteine protease ATG4B;
DE EC=3.4.22.-;
DE AltName: Full=AUT-like 1 cysteine endopeptidase;
DE AltName: Full=Autophagin-1;
DE AltName: Full=Autophagy-related cysteine endopeptidase 1;
DE AltName: Full=Autophagy-related protein 4 homolog B;
DE Short=hAPG4B;
GN Name=ATG4B; Synonyms=APG4B, AUTL1, KIAA0943;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND
RP VARIANT GLN-354.
RC TISSUE=Liver;
RX PubMed=12446702; DOI=10.1074/jbc.M208247200;
RA Marino G., Uria J.A., Puente X.S., Quesada V., Bordallo J.,
RA Lopez-Otin C.;
RT "Human autophagins, a family of cysteine proteinases potentially
RT implicated in cell degradation by autophagy.";
RL J. Biol. Chem. 278:3671-3678(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, FUNCTION
RP IN GABARAPL2; GABARAP AND MAP1LC3A CLEAVAGE, MUTAGENESIS OF CYS-74,
RP AND VARIANT GLN-354.
RX PubMed=15169837; DOI=10.1242/jcs.01131;
RA Kabeya Y., Mizushima N., Yamamoto A., Oshitani-Okamoto S., Ohsumi Y.,
RA Yoshimori T.;
RT "LC3, GABARAP and GATE16 localize to autophagosomal membrane depending
RT on form-II formation.";
RL J. Cell Sci. 117:2805-2812(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
RP GLN-354.
RC TISSUE=Brain;
RX PubMed=10231032; DOI=10.1093/dnares/6.1.63;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M.,
RA Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIII.
RT The complete sequences of 100 new cDNA clones from brain which code
RT for large proteins in vitro.";
RL DNA Res. 6:63-70(1999).
RN [4]
RP SEQUENCE REVISION.
RA Ohara O., Nagase T., Kikuno R.;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 3; 4 AND 6).
RC TISSUE=Embryo, and Placenta;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
RP GLN-354.
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
RP GLN-354.
RC TISSUE=Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP PROTEIN SEQUENCE OF 1-12; 33-49; 120-137; 185-201 AND 230-244,
RP ACETYLATION AT MET-1, AND MASS SPECTROMETRY.
RC TISSUE=Ovarian carcinoma;
RA Bienvenut W.V.;
RL Submitted (JAN-2010) to UniProtKB.
RN [10]
RP FUNCTION, AND MUTAGENESIS OF CYS-74.
RX PubMed=15187094; DOI=10.1074/jbc.M401461200;
RA Tanida I., Sou Y.-S., Ezaki J., Minematsu-Ikeguchi N., Ueno T.,
RA Kominami E.;
RT "HsAtg4B/HsApg4B/autophagin-1 cleaves the carboxyl termini of three
RT human Atg8 homologues and delipidates microtubule-associated protein
RT light chain 3- and GABAA receptor-associated protein-phospholipid
RT conjugates.";
RL J. Biol. Chem. 279:36268-36276(2004).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-383, AND MASS
RP SPECTROMETRY.
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.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [12]
RP FUNCTION, ENZYME REGULATION, AND MUTAGENESIS OF CYS-78.
RX PubMed=17347651; DOI=10.1038/sj.emboj.7601623;
RA Scherz-Shouval R., Shvets E., Fass E., Shorer H., Gil L., Elazar Z.;
RT "Reactive oxygen species are essential for autophagy and specifically
RT regulate the activity of Atg4.";
RL EMBO J. 26:1749-1760(2007).
RN [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-383, AND MASS
RP SPECTROMETRY.
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 [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-383, AND MASS
RP SPECTROMETRY.
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 [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-383, AND MASS
RP SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [18]
RP FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=21177865; DOI=10.1074/jbc.M110.199059;
RA Li M., Hou Y., Wang J., Chen X., Shao Z.M., Yin X.M.;
RT "Kinetics comparisons of mammalian Atg4 homologues indicate selective
RT preferences toward diverse Atg8 substrates.";
RL J. Biol. Chem. 286:7327-7338(2011).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-383, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [20]
RP FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=22302004; DOI=10.4161/auto.18777;
RA Li M., Chen X., Ye Q.Z., Vogt A., Yin X.M.;
RT "A high-throughput FRET-based assay for determination of Atg4
RT activity.";
RL Autophagy 8:401-412(2012).
RN [21]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS), AND MUTAGENESIS OF CYS-74;
RP TRP-142; ARG-229; ASP-278 AND HIS-280.
RX PubMed=16183633; DOI=10.1074/jbc.M509158200;
RA Sugawara K., Suzuki N.N., Fujioka Y., Mizushima N., Ohsumi Y.,
RA Inagaki F.;
RT "Structural basis for the specificity and catalysis of human Atg4B
RT responsible for mammalian autophagy.";
RL J. Biol. Chem. 280:40058-40065(2005).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS), AND MUTAGENESIS OF CYS-74;
RP ASP-278 AND HIS-280.
RX PubMed=16325851; DOI=10.1016/j.jmb.2005.11.018;
RA Kumanomidou T., Mizushima T., Komatsu M., Suzuki A., Tanida I.,
RA Sou Y.-S., Ueno T., Kominami E., Tanaka K., Yamane T.;
RT "The crystal structure of human Atg4b, a processing and de-conjugating
RT enzyme for autophagosome-forming modifiers.";
RL J. Mol. Biol. 355:612-618(2006).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 1-353 IN COMPLEX WITH RAT
RP MAP1LC3B/LC3, AND FUNCTION.
RX PubMed=19322194; DOI=10.1038/emboj.2009.80;
RA Satoo K., Noda N.N., Kumeta H., Fujioka Y., Mizushima N., Ohsumi Y.,
RA Inagaki F.;
RT "The structure of Atg4B-LC3 complex reveals the mechanism of LC3
RT processing and delipidation during autophagy.";
RL EMBO J. 28:1341-1350(2009).
CC -!- FUNCTION: Cysteine protease required for the cytoplasm to vacuole
CC transport (Cvt) and autophagy. Cleaves the C-terminal amino acid
CC of ATG8 family proteins MAP1LC3, GABARAPL1, GABARAPL2 and GABARAP,
CC to reveal a C-terminal glycine. Exposure of the glycine at the C-
CC terminus is essential for ATG8 proteins conjugation to
CC phosphatidylethanolamine (PE) and insertion to membranes, which is
CC necessary for autophagy. Has also an activity of delipidating
CC enzyme for the PE-conjugated forms.
CC -!- ENZYME REGULATION: Inhibited by N-ethylmaleimide. Redox-regulated
CC during autophagy since reducing conditions activate ATG4A whereas
CC an oxidizing environment such as the presence of H(2)O(2) inhibits
CC its activity.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=5.1 uM for MAP1LC3B;
CC KM=5.8 uM for GABARAP;
CC KM=4.4 uM for GABARAPL1;
CC KM=6.1 uM for GABARAPL2;
CC -!- INTERACTION:
CC O95166:GABARAP; NbExp=8; IntAct=EBI-712014, EBI-712001;
CC Q9H0R8:GABARAPL1; NbExp=7; IntAct=EBI-712014, EBI-746969;
CC P60520:GABARAPL2; NbExp=7; IntAct=EBI-712014, EBI-720116;
CC Q9GZQ8:MAP1LC3B; NbExp=11; IntAct=EBI-712014, EBI-373144;
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q9Y4P1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y4P1-2; Sequence=VSP_013029, VSP_013034;
CC Note=No experimental confirmation available;
CC Name=3;
CC IsoId=Q9Y4P1-3; Sequence=VSP_013028, VSP_013031, VSP_013032;
CC Note=No experimental confirmation available;
CC Name=4;
CC IsoId=Q9Y4P1-4; Sequence=VSP_013028, VSP_013033;
CC Name=6;
CC IsoId=Q9Y4P1-6; Sequence=VSP_013034;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Mainly expressed in the skeletal muscle,
CC followed by brain, heart, liver and pancreas.
CC -!- SIMILARITY: Belongs to the peptidase C54 family.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA76787.2; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC Sequence=BAC86110.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
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DR EMBL; AJ504652; CAD43219.1; -; mRNA.
DR EMBL; AB066215; BAB83890.1; -; mRNA.
DR EMBL; AB023160; BAA76787.2; ALT_INIT; mRNA.
DR EMBL; AK027332; BAB55042.1; -; mRNA.
DR EMBL; AK027462; BAB55127.1; -; mRNA.
DR EMBL; AK027763; BAB55353.1; -; mRNA.
DR EMBL; AK125277; BAC86110.1; ALT_INIT; mRNA.
DR EMBL; AL080168; CAB45756.1; -; mRNA.
DR EMBL; AC133528; AAY14919.1; -; Genomic_DNA.
DR EMBL; BC000719; AAH00719.1; -; mRNA.
DR PIR; T12492; T12492.
DR RefSeq; NP_037457.3; NM_013325.4.
DR RefSeq; NP_847896.1; NM_178326.2.
DR UniGene; Hs.283610; -.
DR PDB; 2CY7; X-ray; 1.90 A; A=1-393.
DR PDB; 2D1I; X-ray; 2.00 A; A/B=1-393.
DR PDB; 2Z0D; X-ray; 1.90 A; A=1-353.
DR PDB; 2Z0E; X-ray; 1.90 A; A=1-353.
DR PDB; 2ZZP; X-ray; 2.05 A; A=1-353.
DR PDBsum; 2CY7; -.
DR PDBsum; 2D1I; -.
DR PDBsum; 2Z0D; -.
DR PDBsum; 2Z0E; -.
DR PDBsum; 2ZZP; -.
DR ProteinModelPortal; Q9Y4P1; -.
DR SMR; Q9Y4P1; 10-373.
DR IntAct; Q9Y4P1; 18.
DR MINT; MINT-1414043; -.
DR STRING; 9606.ENSP00000384259; -.
DR BindingDB; Q9Y4P1; -.
DR ChEMBL; CHEMBL1741221; -.
DR MEROPS; C54.003; -.
DR PhosphoSite; Q9Y4P1; -.
DR DMDM; 296434400; -.
DR PaxDb; Q9Y4P1; -.
DR PRIDE; Q9Y4P1; -.
DR DNASU; 23192; -.
DR Ensembl; ENST00000402096; ENSP00000384661; ENSG00000168397.
DR Ensembl; ENST00000404914; ENSP00000384259; ENSG00000168397.
DR Ensembl; ENST00000405546; ENSP00000383964; ENSG00000168397.
DR GeneID; 23192; -.
DR KEGG; hsa:23192; -.
DR UCSC; uc002wbv.3; human.
DR CTD; 23192; -.
DR GeneCards; GC02P242578; -.
DR H-InvDB; HIX0180188; -.
DR HGNC; HGNC:20790; ATG4B.
DR HPA; CAB037195; -.
DR MIM; 611338; gene.
DR neXtProt; NX_Q9Y4P1; -.
DR PharmGKB; PA134898340; -.
DR eggNOG; NOG239662; -.
DR HOVERGEN; HBG050536; -.
DR KO; K08342; -.
DR OMA; RNFPAIG; -.
DR OrthoDB; EOG73V6KD; -.
DR ChiTaRS; ATG4B; human.
DR EvolutionaryTrace; Q9Y4P1; -.
DR GeneWiki; ATG4B; -.
DR GenomeRNAi; 23192; -.
DR NextBio; 44679; -.
DR PRO; PR:Q9Y4P1; -.
DR ArrayExpress; Q9Y4P1; -.
DR Bgee; Q9Y4P1; -.
DR CleanEx; HS_ATG4B; -.
DR Genevestigator; Q9Y4P1; -.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0008234; F:cysteine-type peptidase activity; IDA:UniProtKB.
DR GO; GO:0004175; F:endopeptidase activity; IDA:BHF-UCL.
DR GO; GO:0000045; P:autophagic vacuole assembly; IGI:UniProtKB.
DR GO; GO:0010508; P:positive regulation of autophagy; IDA:BHF-UCL.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
DR InterPro; IPR005078; Peptidase_C54.
DR PANTHER; PTHR22624; PTHR22624; 1.
DR Pfam; PF03416; Peptidase_C54; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Autophagy;
KW Complete proteome; Cytoplasm; Direct protein sequencing; Hydrolase;
KW Phosphoprotein; Polymorphism; Protease; Protein transport;
KW Reference proteome; Thiol protease; Transport;
KW Ubl conjugation pathway.
FT CHAIN 1 393 Cysteine protease ATG4B.
FT /FTId=PRO_0000215844.
FT ACT_SITE 74 74 Nucleophile.
FT ACT_SITE 278 278 Potential.
FT ACT_SITE 280 280
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 383 383 Phosphoserine.
FT VAR_SEQ 1 74 Missing (in isoform 3 and isoform 4).
FT /FTId=VSP_013028.
FT VAR_SEQ 1 1 M -> MAHSVPSDSRTSRRPTTRPHAARGAPRGSRRPGRTP
FT KWRLPRISARAPYRLRRLRRHTYWPPRRPVAASRCWPVGAT
FT PLGSVGGRTGKM (in isoform 2).
FT /FTId=VSP_013029.
FT VAR_SEQ 321 354 FFCKTEDDFNDWCQQVKKLSLLGGALPMFELVEL -> KQG
FT RLVRSLIPWAPRPSSWCAAVLGAAVVMCGTP (in
FT isoform 3).
FT /FTId=VSP_013031.
FT VAR_SEQ 355 393 Missing (in isoform 3).
FT /FTId=VSP_013032.
FT VAR_SEQ 369 369 L -> LGESCQVQVGSLG (in isoform 4).
FT /FTId=VSP_013033.
FT VAR_SEQ 370 393 DSSDVERLERFFDSEDEDFEILSL -> GESCQVQILLM
FT (in isoform 2 and isoform 6).
FT /FTId=VSP_013034.
FT VARIANT 354 354 L -> Q (in dbSNP:rs7601000).
FT /FTId=VAR_021486.
FT MUTAGEN 74 74 C->S: Complete loss of protease activity.
FT MUTAGEN 78 78 C->A: Reduces the redox sensitivity and
FT retains activity in presence of H(2)O(2).
FT MUTAGEN 142 142 W->A: Strongly reduced protease activity.
FT MUTAGEN 229 229 R->A: Strongly reduced protease activity.
FT MUTAGEN 278 278 D->A: Complete loss of protease activity.
FT MUTAGEN 280 280 H->A: Complete loss of protease activity.
FT CONFLICT 136 136 Missing (in Ref. 2; BAB83890).
FT CONFLICT 188 188 P -> L (in Ref. 5; BAB55127).
FT CONFLICT 247 247 F -> Y (in Ref. 5; BAB55353).
FT CONFLICT 273 273 E -> G (in Ref. 5; BAB55042).
FT CONFLICT 312 312 E -> N (in Ref. 2; BAB83890).
FT HELIX 5 7
FT HELIX 10 13
FT HELIX 14 18
FT STRAND 22 24
FT STRAND 26 28
FT STRAND 31 33
FT TURN 35 37
FT HELIX 39 48
FT STRAND 54 57
FT TURN 61 64
FT TURN 70 72
FT HELIX 74 91
FT STRAND 100 102
FT HELIX 106 113
FT STRAND 116 118
FT HELIX 125 133
FT TURN 134 136
FT HELIX 145 156
FT TURN 160 162
FT STRAND 165 168
FT STRAND 173 175
FT HELIX 176 183
FT STRAND 184 186
FT STRAND 222 229
FT STRAND 232 234
FT HELIX 237 239
FT HELIX 240 246
FT STRAND 252 257
FT STRAND 264 270
FT STRAND 273 277
FT STRAND 281 284
FT STRAND 290 292
FT HELIX 297 299
FT STRAND 306 309
FT HELIX 310 312
FT STRAND 315 325
FT HELIX 326 341
FT STRAND 349 353
FT HELIX 371 376
SQ SEQUENCE 393 AA; 44294 MW; F4ADB3192176E0E5 CRC64;
MDAATLTYDT LRFAEFEDFP ETSEPVWILG RKYSIFTEKD EILSDVASRL WFTYRKNFPA
IGGTGPTSDT GWGCMLRCGQ MIFAQALVCR HLGRDWRWTQ RKRQPDSYFS VLNAFIDRKD
SYYSIHQIAQ MGVGEGKSIG QWYGPNTVAQ VLKKLAVFDT WSSLAVHIAM DNTVVMEEIR
RLCRTSVPCA GATAFPADSD RHCNGFPAGA EVTNRPSPWR PLVLLIPLRL GLTDINEAYV
ETLKHCFMMP QSLGVIGGKP NSAHYFIGYV GEELIYLDPH TTQPAVEPTD GCFIPDESFH
CQHPPCRMSI AELDPSIAVG FFCKTEDDFN DWCQQVKKLS LLGGALPMFE LVELQPSHLA
CPDVLNLSLD SSDVERLERF FDSEDEDFEI LSL
//
MIM
611338
*RECORD*
*FIELD* NO
611338
*FIELD* TI
*611338 AUTOPHAGY 4, S. CEREVISIAE, HOMOLOG OF, B; ATG4B
;;APG4, S. CEREVISIAE, HOMOLOG OF, B; APG4B;;
read moreAUTOPHAGIN 1;;
AUTL1;;
KIAA0943
*FIELD* TX
DESCRIPTION
Autophagy is the biologic process leading to intracellular destruction
of endogenous proteins and removal of damaged organelles. ATG4B is a
homolog of yeast Apg4, a cysteine protease involved in autophagy (Marino
et al., 2003).
CLONING
By sequencing clones obtained from a size-fractionated brain cDNA
library, Nagase et al. (1999) cloned ATG4B, which they designated
KIAA0943. The transcript contains a repetitive element in its 3-prime
UTR. RT-PCR ELISA detected moderate expression in all adult and fetal
tissues and specific brain regions examined.
By searching for sequences similar to yeast Apg4, followed by PCR of
human cDNA libraries, Marino et al. (2003) cloned ATG4B, which they
called autophagin-1. The deduced 393-amino acid protein contains a
putative active-site cysteine at position 74. ATG4B shares significant
similarity with yeast Apg4, except for divergence at its N- and
C-terminal ends. The absence of an N-terminal signal sequence suggests
that ATG4B is a cytoplasmic enzyme. Northern blot analysis detected a
4.5-kb transcript that was highly expressed in skeletal muscle, with
lower expression in heart, liver, and pancreas. No expression was
detected in fetal tissues. ATG4B was widely expressed in tumor cell
lines.
GENE FUNCTION
Marino et al. (2003) showed that autophagin-1 could complement Apg4
deficiency in yeast, restoring the phenotypic and biochemical
characteristics of autophagic cells.
Apg8 is a ubiquitin-like protein involved in autophagy in yeast, and
there are at least 4 mammalian Apg8 homologs: GATE16 (GABARAPL2;
607452), GABARAP (605125), MAP1LC3 (see 601242), and APG8L (GABARAPL1;
607420). Hemelaar et al. (2003) found that mouse Atg4b acted on the C
termini of these 4 Atg8 homologs, and that the reaction required the
active-site cysteine of Atg4b. Although the amino acid sequences of
these Apg8 homologs differ from one another by as much as 71%, their
affinities for Atg4b were roughly comparable in competition experiments.
BIOCHEMICAL FEATURES
Sugawara et al. (2005) reported the crystal structure of human ATG4B at
1.9-angstrom resolution. The ATG4B structure showed a classical papain
(see CTSF; 603539)-like fold and a small alpha/beta-fold domain, similar
to those of ubiquitin-specific proteases, that may be the binding site
for Atg8 homologs. The active-site cleft of ATG4B, which contains the
catalytic triad of cys74, asp278, and his280, is masked by a loop,
implying that a conformational change occurs upon substrate binding.
Mutation of cys74, asp278, or his280 resulted in complete loss of
protease activity.
MAPPING
By genomic sequence analysis, Marino et al. (2003) mapped the ATG4B gene
to chromosome 2q37.
*FIELD* RF
1. Hemelaar, J.; Lelyveld, V. S.; Kessler, B. M.; Ploegh, H. L.:
A single protease, Apg4B, is specific for the autophagy-related ubiquitin-like
proteins GATE-16, MAP1-LC3, GABARAP, and Apg8L. J. Biol. Chem. 278:
51841-51850, 2003.
2. Marino, G.; Uria, J. A.; Puente, X. S.; Quesada, V.; Bordallo,
J.; Lopez-Otin, C.: Human autophagins, a family of cysteine proteinases
potentially implicated in cell degradation by autophagy. J. Biol.
Chem. 278: 3671-3678, 2003.
3. Nagase, T.; Ishikawa, K.; Suyama, M.; Kikuno, R.; Hirosawa, M.;
Miyajima, N.; Tanaka, A.; Kotani, H.; Nomura, N.; Ohara, O.: Prediction
of the coding sequences of unidentified human genes. XIII. The complete
sequences of 100 new cDNA clones from brain which code for large proteins
in vitro. DNA Res. 6: 63-70, 1999.
4. Sugawara, K.; Suzuki, N. N.; Fujioka, Y.; Mizushima, N.; Ohsumi,
Y.; Inagaki, F.: Structural basis for the specificity and catalysis
of human Atg4B responsible for the mammalian autophagy. J. Biol.
Chem. 280: 40058-40065, 2005.
*FIELD* CD
Patricia A. Hartz: 8/16/2007
*FIELD* ED
mgross: 08/16/2007
*RECORD*
*FIELD* NO
611338
*FIELD* TI
*611338 AUTOPHAGY 4, S. CEREVISIAE, HOMOLOG OF, B; ATG4B
;;APG4, S. CEREVISIAE, HOMOLOG OF, B; APG4B;;
read moreAUTOPHAGIN 1;;
AUTL1;;
KIAA0943
*FIELD* TX
DESCRIPTION
Autophagy is the biologic process leading to intracellular destruction
of endogenous proteins and removal of damaged organelles. ATG4B is a
homolog of yeast Apg4, a cysteine protease involved in autophagy (Marino
et al., 2003).
CLONING
By sequencing clones obtained from a size-fractionated brain cDNA
library, Nagase et al. (1999) cloned ATG4B, which they designated
KIAA0943. The transcript contains a repetitive element in its 3-prime
UTR. RT-PCR ELISA detected moderate expression in all adult and fetal
tissues and specific brain regions examined.
By searching for sequences similar to yeast Apg4, followed by PCR of
human cDNA libraries, Marino et al. (2003) cloned ATG4B, which they
called autophagin-1. The deduced 393-amino acid protein contains a
putative active-site cysteine at position 74. ATG4B shares significant
similarity with yeast Apg4, except for divergence at its N- and
C-terminal ends. The absence of an N-terminal signal sequence suggests
that ATG4B is a cytoplasmic enzyme. Northern blot analysis detected a
4.5-kb transcript that was highly expressed in skeletal muscle, with
lower expression in heart, liver, and pancreas. No expression was
detected in fetal tissues. ATG4B was widely expressed in tumor cell
lines.
GENE FUNCTION
Marino et al. (2003) showed that autophagin-1 could complement Apg4
deficiency in yeast, restoring the phenotypic and biochemical
characteristics of autophagic cells.
Apg8 is a ubiquitin-like protein involved in autophagy in yeast, and
there are at least 4 mammalian Apg8 homologs: GATE16 (GABARAPL2;
607452), GABARAP (605125), MAP1LC3 (see 601242), and APG8L (GABARAPL1;
607420). Hemelaar et al. (2003) found that mouse Atg4b acted on the C
termini of these 4 Atg8 homologs, and that the reaction required the
active-site cysteine of Atg4b. Although the amino acid sequences of
these Apg8 homologs differ from one another by as much as 71%, their
affinities for Atg4b were roughly comparable in competition experiments.
BIOCHEMICAL FEATURES
Sugawara et al. (2005) reported the crystal structure of human ATG4B at
1.9-angstrom resolution. The ATG4B structure showed a classical papain
(see CTSF; 603539)-like fold and a small alpha/beta-fold domain, similar
to those of ubiquitin-specific proteases, that may be the binding site
for Atg8 homologs. The active-site cleft of ATG4B, which contains the
catalytic triad of cys74, asp278, and his280, is masked by a loop,
implying that a conformational change occurs upon substrate binding.
Mutation of cys74, asp278, or his280 resulted in complete loss of
protease activity.
MAPPING
By genomic sequence analysis, Marino et al. (2003) mapped the ATG4B gene
to chromosome 2q37.
*FIELD* RF
1. Hemelaar, J.; Lelyveld, V. S.; Kessler, B. M.; Ploegh, H. L.:
A single protease, Apg4B, is specific for the autophagy-related ubiquitin-like
proteins GATE-16, MAP1-LC3, GABARAP, and Apg8L. J. Biol. Chem. 278:
51841-51850, 2003.
2. Marino, G.; Uria, J. A.; Puente, X. S.; Quesada, V.; Bordallo,
J.; Lopez-Otin, C.: Human autophagins, a family of cysteine proteinases
potentially implicated in cell degradation by autophagy. J. Biol.
Chem. 278: 3671-3678, 2003.
3. Nagase, T.; Ishikawa, K.; Suyama, M.; Kikuno, R.; Hirosawa, M.;
Miyajima, N.; Tanaka, A.; Kotani, H.; Nomura, N.; Ohara, O.: Prediction
of the coding sequences of unidentified human genes. XIII. The complete
sequences of 100 new cDNA clones from brain which code for large proteins
in vitro. DNA Res. 6: 63-70, 1999.
4. Sugawara, K.; Suzuki, N. N.; Fujioka, Y.; Mizushima, N.; Ohsumi,
Y.; Inagaki, F.: Structural basis for the specificity and catalysis
of human Atg4B responsible for the mammalian autophagy. J. Biol.
Chem. 280: 40058-40065, 2005.
*FIELD* CD
Patricia A. Hartz: 8/16/2007
*FIELD* ED
mgross: 08/16/2007