Full text data of ATG4A
ATG4A
(APG4A, AUTL2)
[Confidence: low (only semi-automatic identification from reviews)]
Cysteine protease ATG4A; 3.4.22.- (AUT-like 2 cysteine endopeptidase; Autophagin-2; Autophagy-related cysteine endopeptidase 2; Autophagy-related protein 4 homolog A; hAPG4A)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Cysteine protease ATG4A; 3.4.22.- (AUT-like 2 cysteine endopeptidase; Autophagin-2; Autophagy-related cysteine endopeptidase 2; Autophagy-related protein 4 homolog A; hAPG4A)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q8WYN0
ID ATG4A_HUMAN Reviewed; 398 AA.
AC Q8WYN0; A6NCH2; B2RAZ7; D3DUY0; O95534; Q5JYY9; Q5JYZ0; Q86VE5;
read moreAC Q96KQ0; Q96KQ1;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 22-JAN-2014, entry version 96.
DE RecName: Full=Cysteine protease ATG4A;
DE EC=3.4.22.-;
DE AltName: Full=AUT-like 2 cysteine endopeptidase;
DE AltName: Full=Autophagin-2;
DE AltName: Full=Autophagy-related cysteine endopeptidase 2;
DE AltName: Full=Autophagy-related protein 4 homolog A;
DE Short=hAPG4A;
GN Name=ATG4A; Synonyms=APG4A, AUTL2;
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), AND TISSUE SPECIFICITY.
RC TISSUE=Ovary;
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), FUNCTION IN GABARAPL2; GABARAP
RP AND MAP1LC3 CLEAVAGE, AND TISSUE SPECIFICITY.
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 [MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Prostate, and Testis;
RA Chen J.M., Barrett A.J.;
RT "Cloning and sequencing of a second human homologue of the yeast Apg4
RT cysteine endopeptidase involved in autophagy.";
RL Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A.,
RA Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G.,
RA Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S.,
RA Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R.,
RA Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L.,
RA Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A.,
RA Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S.,
RA Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R.,
RA Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M.,
RA Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N.,
RA Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D.,
RA Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W.,
RA Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C.,
RA Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C.,
RA Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J.,
RA Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S.,
RA Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I.,
RA Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L.,
RA Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P.,
RA Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S.,
RA Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A.,
RA Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J.,
RA Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J.,
RA Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S.,
RA de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z.,
RA Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C.,
RA Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W.,
RA Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T.,
RA Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I.,
RA Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N.,
RA Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J.,
RA Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E.,
RA Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S.,
RA Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T.,
RA Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S.,
RA Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L.,
RA Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A.,
RA Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L.,
RA Williams G., Williams L., Williamson A., Williamson H., Wilming L.,
RA Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H.,
RA Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A.,
RA Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A.,
RA Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T.,
RA Gibbs R.A., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Kidney, and Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP FUNCTION IN GABARAPL2 CLEAVAGE, AND ENZYME REGULATION.
RX PubMed=12473658; DOI=10.1074/jbc.M212108200;
RA Scherz-Shouval R., Sagiv Y., Shorer H., Elazar Z.;
RT "The COOH terminus of GATE-16, an intra-Golgi transport modulator, is
RT cleaved by the human cysteine protease HsApg4A.";
RL J. Biol. Chem. 278:14053-14058(2003).
RN [9]
RP FUNCTION, ENZYME REGULATION, AND MUTAGENESIS OF CYS-81.
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 [10]
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 [11]
RP FUNCTION.
RX PubMed=21245471; DOI=10.1177/1087057110392996;
RA Shu C.W., Madiraju C., Zhai D., Welsh K., Diaz P., Sergienko E.,
RA Sano R., Reed J.C.;
RT "High-throughput fluorescence assay for small-molecule inhibitors of
RT autophagins/Atg4.";
RL J. Biomol. Screen. 16:174-182(2011).
RN [12]
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 [13]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 23-359.
RA Walker J.R., Davis T., Mujib S., Butler-Cole C., Finerty P.J.,
RA Weigelt J., Sundstrom M., Arrowsmith C.H., Edwards A.M., Bochkarev A.,
RA Dhe-Paganon S.;
RT "Human cysteine protease ATG4A.";
RL Submitted (MAR-2007) to the PDB data bank.
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 to reveal a C-terminal glycine. Exposure
CC of the glycine at the C-terminus is essential for ATG8 proteins
CC conjugation to phosphatidylethanolamine (PE) and insertion to
CC membranes, which is necessary for autophagy. Preferred substrate
CC is GABARAPL2 followed by MAP1LC3A and GABARAP. Has also an
CC activity of delipidating 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=33.9 uM for MAP1LC3B;
CC KM=20.8 uM for GABARAP;
CC KM=36.7 uM for GABARAPL1;
CC KM=15.7 uM for GABARAPL2;
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q8WYN0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8WYN0-2; Sequence=VSP_013025;
CC Name=3;
CC IsoId=Q8WYN0-3; Sequence=VSP_025902;
CC Note=No experimental confirmation available;
CC Name=4;
CC IsoId=Q8WYN0-5; Sequence=VSP_030499;
CC Note=Gene prediction based on EST data;
CC -!- TISSUE SPECIFICITY: Widely expressed, at a low level, and the
CC highest expression is observed in skeletal muscle and brain. Also
CC detected in fetal liver.
CC -!- SIMILARITY: Belongs to the peptidase C54 family.
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DR EMBL; AJ504651; CAD43218.1; -; mRNA.
DR EMBL; AB066214; BAB83889.1; -; mRNA.
DR EMBL; AJ320508; CAC69076.1; -; mRNA.
DR EMBL; AJ320509; CAC69077.1; -; mRNA.
DR EMBL; AK314429; BAG37044.1; -; mRNA.
DR EMBL; AL031177; CAI43137.1; -; Genomic_DNA.
DR EMBL; AL031177; CAI43138.1; -; Genomic_DNA.
DR EMBL; AL031177; CAI43141.1; -; Genomic_DNA.
DR EMBL; AL031177; CAI43142.1; -; Genomic_DNA.
DR EMBL; CH471120; EAX02689.1; -; Genomic_DNA.
DR EMBL; CH471120; EAX02691.1; -; Genomic_DNA.
DR EMBL; CH471120; EAX02693.1; -; Genomic_DNA.
DR EMBL; BC041862; AAH41862.1; -; mRNA.
DR EMBL; BC061696; AAH61696.1; -; mRNA.
DR RefSeq; NP_443168.2; NM_052936.3.
DR RefSeq; NP_840054.1; NM_178270.2.
DR RefSeq; XP_005262120.1; XM_005262063.1.
DR RefSeq; XP_005262121.1; XM_005262064.1.
DR RefSeq; XP_005262122.1; XM_005262065.1.
DR RefSeq; XP_005262123.1; XM_005262066.1.
DR UniGene; Hs.8763; -.
DR PDB; 2FUY; Model; -; A=1-398.
DR PDB; 2P82; X-ray; 2.10 A; A/B/C/D=23-359.
DR PDBsum; 2FUY; -.
DR PDBsum; 2P82; -.
DR ProteinModelPortal; Q8WYN0; -.
DR SMR; Q8WYN0; 26-359.
DR IntAct; Q8WYN0; 2.
DR MINT; MINT-3048289; -.
DR MEROPS; C54.002; -.
DR DMDM; 61211859; -.
DR PaxDb; Q8WYN0; -.
DR PRIDE; Q8WYN0; -.
DR DNASU; 115201; -.
DR Ensembl; ENST00000345734; ENSP00000298131; ENSG00000101844.
DR Ensembl; ENST00000372232; ENSP00000361306; ENSG00000101844.
DR Ensembl; ENST00000372254; ENSP00000361328; ENSG00000101844.
DR GeneID; 115201; -.
DR KEGG; hsa:115201; -.
DR UCSC; uc004enr.3; human.
DR CTD; 115201; -.
DR GeneCards; GC0XP107334; -.
DR HGNC; HGNC:16489; ATG4A.
DR HPA; HPA036374; -.
DR MIM; 300663; gene.
DR neXtProt; NX_Q8WYN0; -.
DR PharmGKB; PA25184; -.
DR eggNOG; NOG239662; -.
DR HOVERGEN; HBG050536; -.
DR InParanoid; Q8WYN0; -.
DR KO; K08342; -.
DR OMA; KGTSAYC; -.
DR OrthoDB; EOG73V6KD; -.
DR PhylomeDB; Q8WYN0; -.
DR EvolutionaryTrace; Q8WYN0; -.
DR GeneWiki; ATG4A; -.
DR GenomeRNAi; 115201; -.
DR NextBio; 79530; -.
DR PRO; PR:Q8WYN0; -.
DR ArrayExpress; Q8WYN0; -.
DR Bgee; Q8WYN0; -.
DR Genevestigator; Q8WYN0; -.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0008234; F:cysteine-type peptidase activity; IDA:UniProtKB.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
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; Alternative splicing; Autophagy; Complete proteome;
KW Cytoplasm; Hydrolase; Protease; Protein transport; Reference proteome;
KW Thiol protease; Transport; Ubl conjugation pathway.
FT CHAIN 1 398 Cysteine protease ATG4A.
FT /FTId=PRO_0000215838.
FT ACT_SITE 77 77 Nucleophile (By similarity).
FT ACT_SITE 279 279 Potential.
FT ACT_SITE 281 281 By similarity.
FT VAR_SEQ 1 77 Missing (in isoform 3).
FT /FTId=VSP_025902.
FT VAR_SEQ 41 64 Missing (in isoform 4).
FT /FTId=VSP_030499.
FT VAR_SEQ 211 272 Missing (in isoform 2).
FT /FTId=VSP_013025.
FT MUTAGEN 81 81 C->A: Reduces the redox sensitivity and
FT retains activity in presence of H(2)O(2).
FT CONFLICT 49 49 I -> Y (in Ref. 7; AAH41862).
FT CONFLICT 218 218 S -> T (in Ref. 3; CAC69076/CAC69077).
FT STRAND 28 31
FT STRAND 34 37
FT TURN 38 41
FT HELIX 42 50
FT STRAND 57 61
FT TURN 64 67
FT TURN 73 75
FT HELIX 77 94
FT HELIX 110 116
FT STRAND 119 121
FT HELIX 128 136
FT TURN 137 139
FT HELIX 148 159
FT TURN 163 165
FT STRAND 168 171
FT STRAND 176 178
FT HELIX 179 186
FT STRAND 223 230
FT STRAND 233 235
FT HELIX 238 240
FT HELIX 241 249
FT STRAND 253 260
FT STRAND 263 271
FT STRAND 274 278
FT STRAND 282 285
FT HELIX 298 300
FT STRAND 307 310
FT HELIX 311 313
FT STRAND 316 326
FT HELIX 327 340
FT TURN 341 343
FT STRAND 344 346
FT STRAND 348 354
SQ SEQUENCE 398 AA; 45378 MW; 3BE892E22E432151 CRC64;
MESVLSKYED QITIFTDYLE EYPDTDELVW ILGKQHLLKT EKSKLLSDIS ARLWFTYRRK
FSPIGGTGPS SDAGWGCMLR CGQMMLAQAL ICRHLGRDWS WEKQKEQPKE YQRILQCFLD
RKDCCYSIHQ MAQMGVGEGK SIGEWFGPNT VAQVLKKLAL FDEWNSLAVY VSMDNTVVIE
DIKKMCRVLP LSADTAGDRP PDSLTASNQS KGTSAYCSAW KPLLLIVPLR LGINQINPVY
VDAFKECFKM PQSLGALGGK PNNAYYFIGF LGDELIFLDP HTTQTFVDTE ENGTVNDQTF
HCLQSPQRMN ILNLDPSVAL GFFCKEEKDF DNWCSLVQKE ILKENLRMFE LVQKHPSHWP
PFVPPAKPEV TTTGAEFIDS TEQLEEFDLE EDFEILSV
//
ID ATG4A_HUMAN Reviewed; 398 AA.
AC Q8WYN0; A6NCH2; B2RAZ7; D3DUY0; O95534; Q5JYY9; Q5JYZ0; Q86VE5;
read moreAC Q96KQ0; Q96KQ1;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 22-JAN-2014, entry version 96.
DE RecName: Full=Cysteine protease ATG4A;
DE EC=3.4.22.-;
DE AltName: Full=AUT-like 2 cysteine endopeptidase;
DE AltName: Full=Autophagin-2;
DE AltName: Full=Autophagy-related cysteine endopeptidase 2;
DE AltName: Full=Autophagy-related protein 4 homolog A;
DE Short=hAPG4A;
GN Name=ATG4A; Synonyms=APG4A, AUTL2;
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), AND TISSUE SPECIFICITY.
RC TISSUE=Ovary;
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), FUNCTION IN GABARAPL2; GABARAP
RP AND MAP1LC3 CLEAVAGE, AND TISSUE SPECIFICITY.
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 [MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Prostate, and Testis;
RA Chen J.M., Barrett A.J.;
RT "Cloning and sequencing of a second human homologue of the yeast Apg4
RT cysteine endopeptidase involved in autophagy.";
RL Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A.,
RA Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G.,
RA Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S.,
RA Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R.,
RA Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L.,
RA Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A.,
RA Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S.,
RA Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R.,
RA Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M.,
RA Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N.,
RA Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D.,
RA Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W.,
RA Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C.,
RA Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C.,
RA Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J.,
RA Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S.,
RA Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I.,
RA Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L.,
RA Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P.,
RA Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S.,
RA Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A.,
RA Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J.,
RA Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J.,
RA Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S.,
RA de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z.,
RA Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C.,
RA Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W.,
RA Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T.,
RA Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I.,
RA Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N.,
RA Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J.,
RA Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E.,
RA Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S.,
RA Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T.,
RA Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S.,
RA Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L.,
RA Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A.,
RA Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L.,
RA Williams G., Williams L., Williamson A., Williamson H., Wilming L.,
RA Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H.,
RA Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A.,
RA Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A.,
RA Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T.,
RA Gibbs R.A., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Kidney, and Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP FUNCTION IN GABARAPL2 CLEAVAGE, AND ENZYME REGULATION.
RX PubMed=12473658; DOI=10.1074/jbc.M212108200;
RA Scherz-Shouval R., Sagiv Y., Shorer H., Elazar Z.;
RT "The COOH terminus of GATE-16, an intra-Golgi transport modulator, is
RT cleaved by the human cysteine protease HsApg4A.";
RL J. Biol. Chem. 278:14053-14058(2003).
RN [9]
RP FUNCTION, ENZYME REGULATION, AND MUTAGENESIS OF CYS-81.
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 [10]
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 [11]
RP FUNCTION.
RX PubMed=21245471; DOI=10.1177/1087057110392996;
RA Shu C.W., Madiraju C., Zhai D., Welsh K., Diaz P., Sergienko E.,
RA Sano R., Reed J.C.;
RT "High-throughput fluorescence assay for small-molecule inhibitors of
RT autophagins/Atg4.";
RL J. Biomol. Screen. 16:174-182(2011).
RN [12]
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 [13]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 23-359.
RA Walker J.R., Davis T., Mujib S., Butler-Cole C., Finerty P.J.,
RA Weigelt J., Sundstrom M., Arrowsmith C.H., Edwards A.M., Bochkarev A.,
RA Dhe-Paganon S.;
RT "Human cysteine protease ATG4A.";
RL Submitted (MAR-2007) to the PDB data bank.
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 to reveal a C-terminal glycine. Exposure
CC of the glycine at the C-terminus is essential for ATG8 proteins
CC conjugation to phosphatidylethanolamine (PE) and insertion to
CC membranes, which is necessary for autophagy. Preferred substrate
CC is GABARAPL2 followed by MAP1LC3A and GABARAP. Has also an
CC activity of delipidating 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=33.9 uM for MAP1LC3B;
CC KM=20.8 uM for GABARAP;
CC KM=36.7 uM for GABARAPL1;
CC KM=15.7 uM for GABARAPL2;
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q8WYN0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8WYN0-2; Sequence=VSP_013025;
CC Name=3;
CC IsoId=Q8WYN0-3; Sequence=VSP_025902;
CC Note=No experimental confirmation available;
CC Name=4;
CC IsoId=Q8WYN0-5; Sequence=VSP_030499;
CC Note=Gene prediction based on EST data;
CC -!- TISSUE SPECIFICITY: Widely expressed, at a low level, and the
CC highest expression is observed in skeletal muscle and brain. Also
CC detected in fetal liver.
CC -!- SIMILARITY: Belongs to the peptidase C54 family.
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DR EMBL; AJ504651; CAD43218.1; -; mRNA.
DR EMBL; AB066214; BAB83889.1; -; mRNA.
DR EMBL; AJ320508; CAC69076.1; -; mRNA.
DR EMBL; AJ320509; CAC69077.1; -; mRNA.
DR EMBL; AK314429; BAG37044.1; -; mRNA.
DR EMBL; AL031177; CAI43137.1; -; Genomic_DNA.
DR EMBL; AL031177; CAI43138.1; -; Genomic_DNA.
DR EMBL; AL031177; CAI43141.1; -; Genomic_DNA.
DR EMBL; AL031177; CAI43142.1; -; Genomic_DNA.
DR EMBL; CH471120; EAX02689.1; -; Genomic_DNA.
DR EMBL; CH471120; EAX02691.1; -; Genomic_DNA.
DR EMBL; CH471120; EAX02693.1; -; Genomic_DNA.
DR EMBL; BC041862; AAH41862.1; -; mRNA.
DR EMBL; BC061696; AAH61696.1; -; mRNA.
DR RefSeq; NP_443168.2; NM_052936.3.
DR RefSeq; NP_840054.1; NM_178270.2.
DR RefSeq; XP_005262120.1; XM_005262063.1.
DR RefSeq; XP_005262121.1; XM_005262064.1.
DR RefSeq; XP_005262122.1; XM_005262065.1.
DR RefSeq; XP_005262123.1; XM_005262066.1.
DR UniGene; Hs.8763; -.
DR PDB; 2FUY; Model; -; A=1-398.
DR PDB; 2P82; X-ray; 2.10 A; A/B/C/D=23-359.
DR PDBsum; 2FUY; -.
DR PDBsum; 2P82; -.
DR ProteinModelPortal; Q8WYN0; -.
DR SMR; Q8WYN0; 26-359.
DR IntAct; Q8WYN0; 2.
DR MINT; MINT-3048289; -.
DR MEROPS; C54.002; -.
DR DMDM; 61211859; -.
DR PaxDb; Q8WYN0; -.
DR PRIDE; Q8WYN0; -.
DR DNASU; 115201; -.
DR Ensembl; ENST00000345734; ENSP00000298131; ENSG00000101844.
DR Ensembl; ENST00000372232; ENSP00000361306; ENSG00000101844.
DR Ensembl; ENST00000372254; ENSP00000361328; ENSG00000101844.
DR GeneID; 115201; -.
DR KEGG; hsa:115201; -.
DR UCSC; uc004enr.3; human.
DR CTD; 115201; -.
DR GeneCards; GC0XP107334; -.
DR HGNC; HGNC:16489; ATG4A.
DR HPA; HPA036374; -.
DR MIM; 300663; gene.
DR neXtProt; NX_Q8WYN0; -.
DR PharmGKB; PA25184; -.
DR eggNOG; NOG239662; -.
DR HOVERGEN; HBG050536; -.
DR InParanoid; Q8WYN0; -.
DR KO; K08342; -.
DR OMA; KGTSAYC; -.
DR OrthoDB; EOG73V6KD; -.
DR PhylomeDB; Q8WYN0; -.
DR EvolutionaryTrace; Q8WYN0; -.
DR GeneWiki; ATG4A; -.
DR GenomeRNAi; 115201; -.
DR NextBio; 79530; -.
DR PRO; PR:Q8WYN0; -.
DR ArrayExpress; Q8WYN0; -.
DR Bgee; Q8WYN0; -.
DR Genevestigator; Q8WYN0; -.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0008234; F:cysteine-type peptidase activity; IDA:UniProtKB.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
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; Alternative splicing; Autophagy; Complete proteome;
KW Cytoplasm; Hydrolase; Protease; Protein transport; Reference proteome;
KW Thiol protease; Transport; Ubl conjugation pathway.
FT CHAIN 1 398 Cysteine protease ATG4A.
FT /FTId=PRO_0000215838.
FT ACT_SITE 77 77 Nucleophile (By similarity).
FT ACT_SITE 279 279 Potential.
FT ACT_SITE 281 281 By similarity.
FT VAR_SEQ 1 77 Missing (in isoform 3).
FT /FTId=VSP_025902.
FT VAR_SEQ 41 64 Missing (in isoform 4).
FT /FTId=VSP_030499.
FT VAR_SEQ 211 272 Missing (in isoform 2).
FT /FTId=VSP_013025.
FT MUTAGEN 81 81 C->A: Reduces the redox sensitivity and
FT retains activity in presence of H(2)O(2).
FT CONFLICT 49 49 I -> Y (in Ref. 7; AAH41862).
FT CONFLICT 218 218 S -> T (in Ref. 3; CAC69076/CAC69077).
FT STRAND 28 31
FT STRAND 34 37
FT TURN 38 41
FT HELIX 42 50
FT STRAND 57 61
FT TURN 64 67
FT TURN 73 75
FT HELIX 77 94
FT HELIX 110 116
FT STRAND 119 121
FT HELIX 128 136
FT TURN 137 139
FT HELIX 148 159
FT TURN 163 165
FT STRAND 168 171
FT STRAND 176 178
FT HELIX 179 186
FT STRAND 223 230
FT STRAND 233 235
FT HELIX 238 240
FT HELIX 241 249
FT STRAND 253 260
FT STRAND 263 271
FT STRAND 274 278
FT STRAND 282 285
FT HELIX 298 300
FT STRAND 307 310
FT HELIX 311 313
FT STRAND 316 326
FT HELIX 327 340
FT TURN 341 343
FT STRAND 344 346
FT STRAND 348 354
SQ SEQUENCE 398 AA; 45378 MW; 3BE892E22E432151 CRC64;
MESVLSKYED QITIFTDYLE EYPDTDELVW ILGKQHLLKT EKSKLLSDIS ARLWFTYRRK
FSPIGGTGPS SDAGWGCMLR CGQMMLAQAL ICRHLGRDWS WEKQKEQPKE YQRILQCFLD
RKDCCYSIHQ MAQMGVGEGK SIGEWFGPNT VAQVLKKLAL FDEWNSLAVY VSMDNTVVIE
DIKKMCRVLP LSADTAGDRP PDSLTASNQS KGTSAYCSAW KPLLLIVPLR LGINQINPVY
VDAFKECFKM PQSLGALGGK PNNAYYFIGF LGDELIFLDP HTTQTFVDTE ENGTVNDQTF
HCLQSPQRMN ILNLDPSVAL GFFCKEEKDF DNWCSLVQKE ILKENLRMFE LVQKHPSHWP
PFVPPAKPEV TTTGAEFIDS TEQLEEFDLE EDFEILSV
//
MIM
300663
*RECORD*
*FIELD* NO
300663
*FIELD* TI
*300663 AUTOPHAGY 4, S. CEREVISIAE, HOMOLOG OF, A; ATG4A
;;APG4, S. CEREVISIAE, HOMOLOG OF, A; APG4A;;
read moreAUTOPHAGIN 2;;
AUTL2
*FIELD* TX
DESCRIPTION
Autophagy is the biologic process leading to intracellular destruction
of endogenous proteins and removal of damaged organelles. ATG4A is a
homolog of yeast Apg4, a cysteine protease involved in autophagy (Marino
et al., 2003).
CLONING
By searching for sequences similar to yeast Apg4, followed by PCR of
human cDNA libraries, Marino et al. (2003) cloned ATG4A, which they
called autophagin-2. The deduced 398-amino acid protein contains a
putative active-site cysteine at position 77. ATG4A 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 ATG4A is a cytoplasmic enzyme. Northern blot analysis detected a
3.2-kb transcript that was highly expressed in skeletal muscle, with
lower expression in fetal liver and other adult tissues.
MAPPING
By genomic sequence analysis, Marino et al. (2003) mapped the ATG4A gene
to chromosome Xq22.
*FIELD* RF
1. 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.
*FIELD* CD
Patricia A. Hartz: 8/16/2007
*FIELD* ED
mgross: 08/16/2007
*RECORD*
*FIELD* NO
300663
*FIELD* TI
*300663 AUTOPHAGY 4, S. CEREVISIAE, HOMOLOG OF, A; ATG4A
;;APG4, S. CEREVISIAE, HOMOLOG OF, A; APG4A;;
read moreAUTOPHAGIN 2;;
AUTL2
*FIELD* TX
DESCRIPTION
Autophagy is the biologic process leading to intracellular destruction
of endogenous proteins and removal of damaged organelles. ATG4A is a
homolog of yeast Apg4, a cysteine protease involved in autophagy (Marino
et al., 2003).
CLONING
By searching for sequences similar to yeast Apg4, followed by PCR of
human cDNA libraries, Marino et al. (2003) cloned ATG4A, which they
called autophagin-2. The deduced 398-amino acid protein contains a
putative active-site cysteine at position 77. ATG4A 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 ATG4A is a cytoplasmic enzyme. Northern blot analysis detected a
3.2-kb transcript that was highly expressed in skeletal muscle, with
lower expression in fetal liver and other adult tissues.
MAPPING
By genomic sequence analysis, Marino et al. (2003) mapped the ATG4A gene
to chromosome Xq22.
*FIELD* RF
1. 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.
*FIELD* CD
Patricia A. Hartz: 8/16/2007
*FIELD* ED
mgross: 08/16/2007