ID ATG4D_HUMAN Reviewed; 474 AA. AC Q86TL0; Q969K0; DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2003, sequence version 1. DT 24-JAN-2024, entry version 158. DE RecName: Full=Cysteine protease ATG4D {ECO:0000305}; DE EC=3.4.22.- {ECO:0000269|PubMed:21177865}; DE AltName: Full=AUT-like 4 cysteine endopeptidase; DE AltName: Full=Autophagy-related cysteine endopeptidase 4 {ECO:0000303|PubMed:12446702}; DE Short=Autophagin-4 {ECO:0000303|PubMed:12446702}; DE AltName: Full=Autophagy-related protein 4 homolog D {ECO:0000305}; DE Short=HsAPG4D {ECO:0000303|PubMed:29458288}; DE Contains: DE RecName: Full=Cysteine protease ATG4D, mitochondrial {ECO:0000305}; GN Name=ATG4D {ECO:0000303|PubMed:19549685, ECO:0000312|HGNC:HGNC:20789}; GN Synonyms=APG4D {ECO:0000312|HGNC:HGNC:20789}, AUTL4 GN {ECO:0000312|HGNC:HGNC:20789}; 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 [LARGE SCALE GENOMIC DNA]. RX PubMed=15057824; DOI=10.1038/nature02399; RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A., RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., RA Rubin E.M., Lucas S.M.; RT "The DNA sequence and biology of human chromosome 19."; RL Nature 428:529-535(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Lung, Ovary, 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 [4] RP RETRACTED PAPER. RC TISSUE=Fetal liver; RX PubMed=12446702; DOI=10.1074/jbc.m208247200; RA Marino G., Uria J.A., Puente X.S., Quesada V., Bordallo J., Lopez-Otin C.; RT "Human autophagins, a family of cysteine proteinases potentially implicated RT in cell degradation by autophagy."; RL J. Biol. Chem. 278:3671-3678(2003). RN [5] RP RETRACTION NOTICE OF PUBMED:12446702. RX PubMed=30808002; DOI=10.1074/jbc.w118.007325; RA Marino G., Uria J.A., Puente X.S., Quesada V., Bordallo J., Lopez-Otin C.; RL J. Biol. Chem. 294:1431-1431(2019). RN [6] RP FUNCTION (CYSTEINE PROTEASE ATG4D; MITOCHONDRIAL), CLEAVAGE BY CASP3, RP MUTAGENESIS OF ASP-63, AND SUBCELLULAR LOCATION. RX PubMed=19549685; DOI=10.1242/jcs.046250; RA Betin V.M., Lane J.D.; RT "Caspase cleavage of Atg4D stimulates GABARAP-L1 processing and triggers RT mitochondrial targeting and apoptosis."; RL J. Cell Sci. 122:2554-2566(2009). RN [7] RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY REGULATION. 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 [8] RP FUNCTION (CYSTEINE PROTEASE ATG4D; MITOCHONDRIAL), CLEAVAGE BY CASP3, RP SUBCELLULAR LOCATION, DOMAIN, AND CRYPTIC SIGNAL PEPTIDE. RX PubMed=22441018; DOI=10.4161/auto.19227; RA Betin V.M., MacVicar T.D., Parsons S.F., Anstee D.J., Lane J.D.; RT "A cryptic mitochondrial targeting motif in Atg4D links caspase cleavage RT with mitochondrial import and oxidative stress."; RL Autophagy 8:664-676(2012). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-467, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE 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 [10] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=29458288; DOI=10.1080/15548627.2018.1437341; RA Kauffman K.J., Yu S., Jin J., Mugo B., Nguyen N., O'Brien A., Nag S., RA Lystad A.H., Melia T.J.; RT "Delipidation of mammalian Atg8-family proteins by each of the four ATG4 RT proteases."; RL Autophagy 14:992-1010(2018). RN [11] RP FUNCTION. RX PubMed=30661429; DOI=10.1080/15548627.2019.1569925; RA Agrotis A., Pengo N., Burden J.J., Ketteler R.; RT "Redundancy of human ATG4 protease isoforms in autophagy and LC3/GABARAP RT processing revealed in cells."; RL Autophagy 15:976-997(2019). RN [12] RP FUNCTION. RX PubMed=33773106; DOI=10.1016/j.molcel.2021.03.001; RA Nguyen T.N., Padman B.S., Zellner S., Khuu G., Uoselis L., Lam W.K., RA Skulsuppaisarn M., Lindblom R.S.J., Watts E.M., Behrends C., Lazarou M.; RT "ATG4 family proteins drive phagophore growth independently of the RT LC3/GABARAP lipidation system."; RL Mol. Cell 81:2013-2030(2021). RN [13] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=33909989; DOI=10.1016/j.molcel.2021.03.020; RA Durgan J., Lystad A.H., Sloan K., Carlsson S.R., Wilson M.I., Marcassa E., RA Ulferts R., Webster J., Lopez-Clavijo A.F., Wakelam M.J., Beale R., RA Simonsen A., Oxley D., Florey O.; RT "Non-canonical autophagy drives alternative ATG8 conjugation to RT phosphatidylserine."; RL Mol. Cell 81:2031-2040(2021). RN [14] RP VARIANTS LEU-125; ILE-273; ASP-295 AND MET-395, CHARACTERIZATION OF VARIANT RP LEU-125, AND TISSUE SPECIFICITY. RX PubMed=33988247; DOI=10.1111/cge.13995; RA Sha Y., Liu W., Wei X., Zhu X., Tang B., Zhang X., Yang X., Wang Y., RA Wang X.; RT "Pathogenic variants of ATG4D in infertile men with non-obstructive RT azoospermia identified using whole-exome sequencing."; RL Clin. Genet. 100:280-291(2021). CC -!- FUNCTION: [Cysteine protease ATG4D]: Cysteine protease that plays a key CC role in autophagy by mediating both proteolytic activation and CC delipidation of ATG8 family proteins (PubMed:21177865, PubMed:29458288, CC PubMed:30661429). The protease activity is required for proteolytic CC activation of ATG8 family proteins: cleaves the C-terminal amino acid CC of ATG8 proteins MAP1LC3 and GABARAPL2, to reveal a C-terminal glycine CC (PubMed:21177865). Exposure of the glycine at the C-terminus is CC essential for ATG8 proteins conjugation to phosphatidylethanolamine CC (PE) and insertion to membranes, which is necessary for autophagy (By CC similarity). In addition to the protease activity, also mediates CC delipidation of ATG8 family proteins (PubMed:29458288, CC PubMed:33909989). Catalyzes delipidation of PE-conjugated forms of ATG8 CC proteins during macroautophagy (PubMed:29458288, PubMed:33909989). Also CC involved in non-canonical autophagy, a parallel pathway involving CC conjugation of ATG8 proteins to single membranes at endolysosomal CC compartments, by catalyzing delipidation of ATG8 proteins conjugated to CC phosphatidylserine (PS) (PubMed:33909989). ATG4D plays a role in the CC autophagy-mediated neuronal homeostasis in the central nervous system CC (By similarity). Compared to other members of the family (ATG4A, ATG4B CC or ATG4C), constitutes the major protein for the delipidation activity, CC while it promotes weak proteolytic activation of ATG8 proteins (By CC similarity). Involved in phagophore growth during mitophagy CC independently of its protease activity and of ATG8 proteins: acts by CC regulating ATG9A trafficking to mitochondria and promoting phagophore- CC endoplasmic reticulum contacts during the lipid transfer phase of CC mitophagy (PubMed:33773106). {ECO:0000250|UniProtKB:Q8BGV9, CC ECO:0000250|UniProtKB:Q9Y4P1, ECO:0000269|PubMed:21177865, CC ECO:0000269|PubMed:29458288, ECO:0000269|PubMed:30661429, CC ECO:0000269|PubMed:33773106, ECO:0000269|PubMed:33909989}. CC -!- FUNCTION: [Cysteine protease ATG4D, mitochondrial]: Plays a role as an CC autophagy regulator that links mitochondrial dysfunction with CC apoptosis. The mitochondrial import of ATG4D during cellular stress and CC differentiation may play important roles in the regulation of CC mitochondrial physiology, ROS, mitophagy and cell viability. CC {ECO:0000269|PubMed:19549685, ECO:0000269|PubMed:22441018}. CC -!- CATALYTIC ACTIVITY: CC Reaction=[protein]-C-terminal L-amino acid-glycyl- CC phosphatidylethanolamide + H2O = [protein]-C-terminal L-amino acid- CC glycine + a 1,2-diacyl-sn-glycero-3-phosphoethanolamine; CC Xref=Rhea:RHEA:67548, Rhea:RHEA-COMP:17323, Rhea:RHEA-COMP:17324, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:64612, ChEBI:CHEBI:172940, CC ChEBI:CHEBI:172941; Evidence={ECO:0000269|PubMed:29458288, CC ECO:0000269|PubMed:33909989}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67549; CC Evidence={ECO:0000269|PubMed:29458288, ECO:0000269|PubMed:33909989}; CC -!- CATALYTIC ACTIVITY: CC Reaction=[protein]-C-terminal L-amino acid-glycyl-phosphatidylserine + CC H2O = [protein]-C-terminal L-amino acid-glycine + a 1,2-diacyl-sn- CC glycero-3-phospho-L-serine; Xref=Rhea:RHEA:67576, Rhea:RHEA- CC COMP:17324, Rhea:RHEA-COMP:17326, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:57262, ChEBI:CHEBI:172940, ChEBI:CHEBI:172942; CC Evidence={ECO:0000269|PubMed:33909989}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67577; CC Evidence={ECO:0000269|PubMed:33909989}; CC -!- ACTIVITY REGULATION: Inhibited by N-ethylmaleimide. CC {ECO:0000269|PubMed:21177865}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=13.1 uM for MAP1LC3B {ECO:0000269|PubMed:21177865}; CC KM=7.2 uM for GABARAPL2 {ECO:0000269|PubMed:21177865}; CC -!- SUBCELLULAR LOCATION: [Cysteine protease ATG4D]: Cytoplasm CC {ECO:0000269|PubMed:19549685}. CC -!- SUBCELLULAR LOCATION: [Cysteine protease ATG4D, mitochondrial]: CC Cytoplasm {ECO:0000269|PubMed:19549685}. Mitochondrion matrix CC {ECO:0000269|PubMed:19549685, ECO:0000269|PubMed:22441018}. CC Note=Imported into mitochondrial matrix after cleavage by CASP3 during CC oxidative stress and cell death. {ECO:0000269|PubMed:22441018}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q86TL0-1; Sequence=Displayed; CC Name=2; CC IsoId=Q86TL0-2; Sequence=VSP_056671; CC -!- TISSUE SPECIFICITY: Widely expressed in testis. CC {ECO:0000269|PubMed:33988247}. CC -!- DOMAIN: The cryptic mitochondrial transit peptide is revealed after CC cleavage by caspase upon oxidative stress and cell death CC (PubMed:22441018). It acts then as a functional transit peptide, and CC allows the import of the cleaved protein into the mitochondria CC (PubMed:22441018). {ECO:0000269|PubMed:22441018}. CC -!- PTM: Cleaved by CASP3 during apoptosis which leads to increased CC activity (PubMed:19549685, PubMed:22441018). The cleavage by CASP3 CC reveals a cryptic mitochondrial targeting sequence immediately CC downstream of their canonical caspase cleavage sites which leads to CC mitochondrial import of the protein (PubMed:19549685, PubMed:22441018). CC {ECO:0000269|PubMed:19549685, ECO:0000269|PubMed:22441018}. CC -!- SIMILARITY: Belongs to the peptidase C54 family. {ECO:0000305}. CC -!- CAUTION: A paper describing ATG4D tissue expression has been retracted, CC due to concerns of image duplication in some of the figures. CC {ECO:0000269|PubMed:12446702, ECO:0000305|PubMed:30808002}. 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; AJ312332; CAC85951.1; -; mRNA. DR EMBL; AC011461; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471106; EAW84116.1; -; Genomic_DNA. DR EMBL; BC007639; AAH07639.1; -; mRNA. DR EMBL; BC016845; AAH16845.1; -; mRNA. DR EMBL; BC068992; AAH68992.1; -; mRNA. DR CCDS; CCDS12241.1; -. [Q86TL0-1] DR RefSeq; NP_001268433.1; NM_001281504.1. DR RefSeq; NP_116274.3; NM_032885.5. [Q86TL0-1] DR AlphaFoldDB; Q86TL0; -. DR SMR; Q86TL0; -. DR BioGRID; 124401; 13. DR IntAct; Q86TL0; 3. DR STRING; 9606.ENSP00000311318; -. DR MEROPS; C54.005; -. DR TCDB; 9.A.15.2.1; the autophagy-related phagophore-formation transporter (apt) family. DR GlyGen; Q86TL0; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q86TL0; -. DR PhosphoSitePlus; Q86TL0; -. DR BioMuta; ATG4D; -. DR DMDM; 61211809; -. DR EPD; Q86TL0; -. DR jPOST; Q86TL0; -. DR MassIVE; Q86TL0; -. DR MaxQB; Q86TL0; -. DR PaxDb; 9606-ENSP00000311318; -. DR PeptideAtlas; Q86TL0; -. DR ProteomicsDB; 69710; -. [Q86TL0-1] DR ProteomicsDB; 75778; -. DR Antibodypedia; 25362; 713 antibodies from 37 providers. DR DNASU; 84971; -. DR Ensembl; ENST00000309469.9; ENSP00000311318.3; ENSG00000130734.10. [Q86TL0-1] DR GeneID; 84971; -. DR KEGG; hsa:84971; -. DR MANE-Select; ENST00000309469.9; ENSP00000311318.3; NM_032885.6; NP_116274.3. DR UCSC; uc002mov.5; human. [Q86TL0-1] DR AGR; HGNC:20789; -. DR CTD; 84971; -. DR DisGeNET; 84971; -. DR GeneCards; ATG4D; -. DR HGNC; HGNC:20789; ATG4D. DR HPA; ENSG00000130734; Low tissue specificity. DR MIM; 611340; gene. DR neXtProt; NX_Q86TL0; -. DR OpenTargets; ENSG00000130734; -. DR PharmGKB; PA134907475; -. DR VEuPathDB; HostDB:ENSG00000130734; -. DR eggNOG; KOG2674; Eukaryota. DR GeneTree; ENSGT00530000063000; -. DR HOGENOM; CLU_021259_3_2_1; -. DR InParanoid; Q86TL0; -. DR OMA; PMEATHR; -. DR OrthoDB; 276806at2759; -. DR PhylomeDB; Q86TL0; -. DR TreeFam; TF314847; -. DR PathwayCommons; Q86TL0; -. DR Reactome; R-HSA-1632852; Macroautophagy. DR SABIO-RK; Q86TL0; -. DR SignaLink; Q86TL0; -. DR BioGRID-ORCS; 84971; 10 hits in 1152 CRISPR screens. DR ChiTaRS; ATG4D; human. DR GenomeRNAi; 84971; -. DR Pharos; Q86TL0; Tbio. DR PRO; PR:Q86TL0; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; Q86TL0; Protein. DR Bgee; ENSG00000130734; Expressed in mucosa of transverse colon and 97 other cell types or tissues. DR ExpressionAtlas; Q86TL0; baseline and differential. DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell. DR GO; GO:0005739; C:mitochondrion; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0070004; F:cysteine-type exopeptidase activity; IDA:UniProt. DR GO; GO:0008234; F:cysteine-type peptidase activity; IDA:UniProtKB. DR GO; GO:0019786; F:protein-phosphatidylethanolamide deconjugating activity; IEA:InterPro. DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW. DR GO; GO:0000045; P:autophagosome assembly; IDA:UniProt. DR GO; GO:0006914; P:autophagy; IDA:UniProtKB. DR GO; GO:0000423; P:mitophagy; IMP:UniProtKB. DR GO; GO:0051697; P:protein delipidation; IDA:UniProtKB. DR GO; GO:0034497; P:protein localization to phagophore assembly site; IMP:UniProtKB. DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW. DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB. DR InterPro; IPR038765; Papain-like_cys_pep_sf. DR InterPro; IPR005078; Peptidase_C54. DR InterPro; IPR046792; Peptidase_C54_cat. DR PANTHER; PTHR22624; CYSTEINE PROTEASE ATG4; 1. DR PANTHER; PTHR22624:SF36; CYSTEINE PROTEASE ATG4D; 1. DR Pfam; PF03416; Peptidase_C54; 1. DR SUPFAM; SSF54001; Cysteine proteinases; 1. DR Genevisible; Q86TL0; HS. PE 1: Evidence at protein level; KW Alternative splicing; Apoptosis; Autophagy; Cytoplasm; Hydrolase; KW Mitochondrion; Phosphoprotein; Protease; Protein transport; KW Reference proteome; Thiol protease; Transport; Ubl conjugation pathway. FT CHAIN 1..474 FT /note="Cysteine protease ATG4D" FT /id="PRO_0000215853" FT CHAIN 64..474 FT /note="Cysteine protease ATG4D, mitochondrial" FT /id="PRO_0000423408" FT REGION 1..60 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 64..103 FT /note="Cryptic mitochondrial signal peptide" FT COMPBIAS 15..31 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 144 FT /note="Nucleophile" FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1" FT ACT_SITE 356 FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1" FT ACT_SITE 358 FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1" FT SITE 63..64 FT /note="Cleavage; by CASP3" FT /evidence="ECO:0000269|PubMed:19549685" FT MOD_RES 467 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 1..333 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_056671" FT VARIANT 125 FT /note="R -> L (found in patients with non-obstructive FT azoospermia; uncertain significance; decreased expression FT of MAP1LC3B; increased programmed cell death in FT spermatogenic cells; dbSNP:rs1216040637)" FT /evidence="ECO:0000269|PubMed:33988247" FT /id="VAR_085353" FT VARIANT 273 FT /note="V -> I (found in patients with non-obstructive FT azoospermia; uncertain significance; dbSNP:rs145807760)" FT /evidence="ECO:0000269|PubMed:33988247" FT /id="VAR_085354" FT VARIANT 295 FT /note="A -> D (found in patients with non-obstructive FT azoospermia; uncertain significance; dbSNP:rs1261979779)" FT /evidence="ECO:0000269|PubMed:33988247" FT /id="VAR_085355" FT VARIANT 395 FT /note="V -> M (found in patients with non-obstructive FT azoospermia; uncertain significance; dbSNP:rs201291151)" FT /evidence="ECO:0000269|PubMed:33988247" FT /id="VAR_085356" FT MUTAGEN 63 FT /note="D->A: Abolishes cleavage by CASP3." FT /evidence="ECO:0000269|PubMed:19549685" SQ SEQUENCE 474 AA; 52922 MW; DBD91A3F1F80D2B8 CRC64; MNSVSPAAAQ YRSSSPEDAR RRPEARRPRG PRGPDPNGLG PSGASGPALG SPGAGPSEPD EVDKFKAKFL TAWNNVKYGW VVKSRTSFSK ISSIHLCGRR YRFEGEGDIQ RFQRDFVSRL WLTYRRDFPP LPGGCLTSDC GWGCMLRSGQ MMLAQGLLLH FLPRDWTWAE GMGLGPPELS GSASPSRYHG PARWMPPRWA QGAPELEQER RHRQIVSWFA DHPRAPFGLH RLVELGQSSG KKAGDWYGPS LVAHILRKAV ESCSDVTRLV VYVSQDCTVY KADVARLVAR PDPTAEWKSV VILVPVRLGG ETLNPVYVPC VKELLRCELC LGIMGGKPRH SLYFIGYQDD FLLYLDPHYC QPTVDVSQAD FPLESFHCTS PRKMAFAKMD PSCTVGFYAG DRKEFETLCS ELTRVLSSSS ATERYPMFTL AEGHAQDHSL DDLCSQLAQP TLRLPRTGRL LRAKRPSSED FVFL //