ATG4D_HUMAN
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 03-AUG-2022, entry version 150.
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},
GN AUTL4 {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}.
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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; 12.
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 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; Q86TL0; -.
DR PeptideAtlas; Q86TL0; -.
DR PRIDE; Q86TL0; -.
DR ProteomicsDB; 69710; -. [Q86TL0-1]
DR ProteomicsDB; 75778; -.
DR Antibodypedia; 25362; 639 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 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; 58543at2759; -.
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 1076 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 95 other tissues.
DR ExpressionAtlas; Q86TL0; baseline and differential.
DR Genevisible; Q86TL0; HS.
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:0008234; F:cysteine-type peptidase activity; IDA:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
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 PANTHER; PTHR22624; PTHR22624; 1.
DR Pfam; PF03416; Peptidase_C54; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
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; unknown pathological significance; decreased
FT expression 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; unknown pathological significance;
FT 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; unknown pathological significance;
FT 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; unknown pathological significance;
FT 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
