LOCUS       NM_032885               1963 bp    mRNA    linear   PRI 06-JUN-2024
DEFINITION  Homo sapiens autophagy related 4D cysteine peptidase (ATG4D),
            transcript variant 1, mRNA.
ACCESSION   NM_032885
VERSION     NM_032885.6
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 1963)
  AUTHORS   Zhao,J.Y., Li,X.Y., Liu,T.D., Liang,B., Huang,Y. and Li,W.
  TITLE     Silencing of ATG4D suppressed proliferation and enhanced
            cisplatin-induced apoptosis in hepatocellular carcinoma through
            Akt/Caspase-3 pathway
  JOURNAL   Mol Cell Biochem 476 (11), 4153-4159 (2021)
   PUBMED   34313895
  REMARK    GeneRIF: Silencing of ATG4D suppressed proliferation and enhanced
            cisplatin-induced apoptosis in hepatocellular carcinoma through
            Akt/Caspase-3 pathway.
REFERENCE   2  (bases 1 to 1963)
  AUTHORS   Sha,Y., Liu,W., Wei,X., Zhu,X., Tang,B., Zhang,X., Yang,X., Wang,Y.
            and Wang,X.
  TITLE     Pathogenic variants of ATG4D in infertile men with non-obstructive
            azoospermia identified using whole-exome sequencing
  JOURNAL   Clin Genet 100 (3), 280-291 (2021)
   PUBMED   33988247
  REMARK    GeneRIF: Pathogenic variants of ATG4D in infertile men with
            non-obstructive azoospermia identified using whole-exome
            sequencing.
REFERENCE   3  (bases 1 to 1963)
  AUTHORS   Nguyen,T.N., Padman,B.S., Zellner,S., Khuu,G., Uoselis,L.,
            Lam,W.K., Skulsuppaisarn,M., Lindblom,R.S.J., Watts,E.M.,
            Behrends,C. and Lazarou,M.
  TITLE     ATG4 family proteins drive phagophore growth independently of the
            LC3/GABARAP lipidation system
  JOURNAL   Mol Cell 81 (9), 2013-2030 (2021)
   PUBMED   33773106
  REMARK    GeneRIF: ATG4 family proteins drive phagophore growth independently
            of the LC3/GABARAP lipidation system.
REFERENCE   4  (bases 1 to 1963)
  AUTHORS   Agrotis,A., Pengo,N., Burden,J.J. and Ketteler,R.
  TITLE     Redundancy of human ATG4 protease isoforms in autophagy and
            LC3/GABARAP processing revealed in cells
  JOURNAL   Autophagy 15 (6), 976-997 (2019)
   PUBMED   30661429
  REMARK    GeneRIF: Human HAP1 and HeLa cells lacking ATG4B exhibit a severe
            but incomplete defect in LC3/GABARAP processing and autophagy. By
            further genetic depletion of ATG4 isoforms using CRISPR-Cas9 and
            siRNA we uncover that ATG4A, ATG4C and ATGD all contribute to
            residual priming activity, which is sufficient to enable lipidation
            of endogenous GABARAPL1 on autophagic structures.
REFERENCE   5  (bases 1 to 1963)
  AUTHORS   Gil,J., Ramsey,D., Pawlowski,P., Szmida,E., Leszczynski,P.,
            Bebenek,M. and Sasiadek,M.M.
  TITLE     The Influence of Tumor Microenvironment on ATG4D Gene Expression in
            Colorectal Cancer Patients
  JOURNAL   Med Oncol 35 (12), 159 (2018)
   PUBMED   30374741
  REMARK    GeneRIF: High ATG4D expression is associated with Colorectal
            Cancer.
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 1963)
  AUTHORS   Zhang,X., Li,C., Wang,D., Chen,Q., Li,C.L. and Li,H.J.
  TITLE     Aberrant methylation of ATG2B, ATG4D, ATG9A and ATG9B CpG island
            promoter is associated with decreased mRNA expression in sporadic
            breast carcinoma
  JOURNAL   Gene 590 (2), 285-292 (2016)
   PUBMED   27265029
  REMARK    GeneRIF: This study highlights the transcriptional inactivation
            mechanisms of ATG2B, ATG4D, ATG9A and ATG9B promoter methylation
            status and the possible origin of autophagy signal pathway
            repression in invasive ductal carcinomas.
REFERENCE   7  (bases 1 to 1963)
  AUTHORS   Betin,V.M., Singleton,B.K., Parsons,S.F., Anstee,D.J. and Lane,J.D.
  TITLE     Autophagy facilitates organelle clearance during differentiation of
            human erythroblasts: evidence for a role for ATG4 paralogs during
            autophagosome maturation
  JOURNAL   Autophagy 9 (6), 881-893 (2013)
   PUBMED   23508006
  REMARK    GeneRIF: The actions of ATG4 family members (particularly ATG4B)
            are required for the control of autophagosome fusion with late,
            degradative compartments in differentiating human erythroblasts.
REFERENCE   8  (bases 1 to 1963)
  AUTHORS   Betin,V.M., MacVicar,T.D., Parsons,S.F., Anstee,D.J. and Lane,J.D.
  TITLE     A cryptic mitochondrial targeting motif in Atg4D links caspase
            cleavage with mitochondrial import and oxidative stress
  JOURNAL   Autophagy 8 (4), 664-676 (2012)
   PUBMED   22441018
  REMARK    GeneRIF: the import of Atg4D during cellular stress and
            differentiation may play important roles in the regulation of
            mitochondrial physiology, reactive oxygen species, mitophagy and
            cell viability.
REFERENCE   9  (bases 1 to 1963)
  AUTHORS   Li,M., Hou,Y., Wang,J., Chen,X., Shao,Z.M. and Yin,X.M.
  TITLE     Kinetics comparisons of mammalian Atg4 homologues indicate
            selective preferences toward diverse Atg8 substrates
  JOURNAL   J Biol Chem 286 (9), 7327-7338 (2011)
   PUBMED   21177865
REFERENCE   10 (bases 1 to 1963)
  AUTHORS   Betin,V.M. and Lane,J.D.
  TITLE     Caspase cleavage of Atg4D stimulates GABARAP-L1 processing and
            triggers mitochondrial targeting and apoptosis
  JOURNAL   J Cell Sci 122 (Pt 14), 2554-2566 (2009)
   PUBMED   19549685
  REMARK    GeneRIF: Caspase cleavage of Atg4D stimulates GABARAP-L1 processing
            and triggers mitochondrial targeting and apoptosis.
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from HY063028.1 and BC068992.1.
            
            On Nov 22, 2018 this sequence version replaced NM_032885.5.
            
            Summary: Autophagy is the process by which endogenous proteins and
            damaged organelles are destroyed intracellularly. Autophagy is
            postulated to be essential for cell homeostasis and cell remodeling
            during differentiation, metamorphosis, non-apoptotic cell death,
            and aging. Reduced levels of autophagy have been described in some
            malignant tumors, and a role for autophagy in controlling the
            unregulated cell growth linked to cancer has been proposed. This
            gene belongs to the autophagy-related protein 4 (Atg4) family of
            C54 endopeptidases. Members of this family encode proteins that
            play a role in the biogenesis of autophagosomes, which sequester
            the cytosol and organelles for degradation by lysosomes.
            Alternative splicing results in multiple transcript variants.
            [provided by RefSeq, Jul 2013].
            
            Transcript Variant: This variant (1) encodes the longer isoform
            (1).
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: SRR3476690.908948.1, AK056210.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: PMID: 22441018
            MANE Ensembl match                 :: ENST00000309469.9/
                                                  ENSP00000311318.3
            RefSeq Select criteria             :: based on conservation,
                                                  expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-14                HY063028.1         12-25
            15-1963             BC068992.1         1-1949
FEATURES             Location/Qualifiers
     source          1..1963
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="19"
                     /map="19p13.2"
     gene            1..1963
                     /gene="ATG4D"
                     /gene_synonym="APG4-D; APG4D; AUTL4; HsAPG4D"
                     /note="autophagy related 4D cysteine peptidase"
                     /db_xref="GeneID:84971"
                     /db_xref="HGNC:HGNC:20789"
                     /db_xref="MIM:611340"
     exon            1..422
                     /gene="ATG4D"
                     /gene_synonym="APG4-D; APG4D; AUTL4; HsAPG4D"
                     /inference="alignment:Splign:2.1.0"
     CDS             188..1612
                     /gene="ATG4D"
                     /gene_synonym="APG4-D; APG4D; AUTL4; HsAPG4D"
                     /note="isoform 1 precursor is encoded by transcript
                     variant 1; autophagin-4; ATG4 autophagy related 4 homolog
                     D; cysteine protease involved in autophagy;
                     autophagy-related cysteine endopeptidase 4; cysteine
                     protease ATG4D; AUT-like 4 cysteine endopeptidase;
                     autophagy-related protein 4 homolog D; APG4 autophagy 4
                     homolog D"
                     /codon_start=1
                     /product="cysteine protease ATG4D isoform 1 precursor"
                     /protein_id="NP_116274.3"
                     /db_xref="CCDS:CCDS12241.1"
                     /db_xref="GeneID:84971"
                     /db_xref="HGNC:HGNC:20789"
                     /db_xref="MIM:611340"
                     /translation="MNSVSPAAAQYRSSSPEDARRRPEARRPRGPRGPDPNGLGPSGA
                     SGPALGSPGAGPSEPDEVDKFKAKFLTAWNNVKYGWVVKSRTSFSKISSIHLCGRRYR
                     FEGEGDIQRFQRDFVSRLWLTYRRDFPPLPGGCLTSDCGWGCMLRSGQMMLAQGLLLH
                     FLPRDWTWAEGMGLGPPELSGSASPSRYHGPARWMPPRWAQGAPELEQERRHRQIVSW
                     FADHPRAPFGLHRLVELGQSSGKKAGDWYGPSLVAHILRKAVESCSDVTRLVVYVSQD
                     CTVYKADVARLVARPDPTAEWKSVVILVPVRLGGETLNPVYVPCVKELLRCELCLGIM
                     GGKPRHSLYFIGYQDDFLLYLDPHYCQPTVDVSQADFPLESFHCTSPRKMAFAKMDPS
                     CTVGFYAGDRKEFETLCSELTRVLSSSSATERYPMFTLAEGHAQDHSLDDLCSQLAQP
                     TLRLPRTGRLLRAKRPSSEDFVFL"
     exon            423..506
                     /gene="ATG4D"
                     /gene_synonym="APG4-D; APG4D; AUTL4; HsAPG4D"
                     /inference="alignment:Splign:2.1.0"
     exon            507..680
                     /gene="ATG4D"
                     /gene_synonym="APG4-D; APG4D; AUTL4; HsAPG4D"
                     /inference="alignment:Splign:2.1.0"
     exon            681..957
                     /gene="ATG4D"
                     /gene_synonym="APG4-D; APG4D; AUTL4; HsAPG4D"
                     /inference="alignment:Splign:2.1.0"
     exon            958..1022
                     /gene="ATG4D"
                     /gene_synonym="APG4-D; APG4D; AUTL4; HsAPG4D"
                     /inference="alignment:Splign:2.1.0"
     exon            1023..1153
                     /gene="ATG4D"
                     /gene_synonym="APG4-D; APG4D; AUTL4; HsAPG4D"
                     /inference="alignment:Splign:2.1.0"
     exon            1154..1232
                     /gene="ATG4D"
                     /gene_synonym="APG4-D; APG4D; AUTL4; HsAPG4D"
                     /inference="alignment:Splign:2.1.0"
     exon            1233..1309
                     /gene="ATG4D"
                     /gene_synonym="APG4-D; APG4D; AUTL4; HsAPG4D"
                     /inference="alignment:Splign:2.1.0"
     exon            1310..1429
                     /gene="ATG4D"
                     /gene_synonym="APG4-D; APG4D; AUTL4; HsAPG4D"
                     /inference="alignment:Splign:2.1.0"
     exon            1430..1963
                     /gene="ATG4D"
                     /gene_synonym="APG4-D; APG4D; AUTL4; HsAPG4D"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1944..1949
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ATG4D"
                     /gene_synonym="APG4-D; APG4D; AUTL4; HsAPG4D"
                     /note="hexamer: AATAAA"
     polyA_site      1963
                     /gene="ATG4D"
                     /gene_synonym="APG4-D; APG4D; AUTL4; HsAPG4D"
                     /note="major polyA site"
ORIGIN      
        1 gtcctggccc gctaagatgg cgatggctgc ggtagcagcg gcggcggctg ttgcctggcc
       61 cggtaccctg gggacggggg ccgagtagcg ccttccccgg gccccgtgaa ccggctgcgg
      121 gtcgcccttg gggggcagcg gccgcagccc cccacctggg ccctcggtcc gccctcccgg
      181 cgcgtccatg aactcagtgt cgccggccgc cgcgcagtac cggagcagca gcccggagga
      241 cgcgcgccgc cggcccgagg cccgcaggcc gcggggtccc agaggcccag accccaacgg
      301 cctggggcct tccggagcca gcggccccgc tcttggctct cccggggctg gcccgagtga
      361 gccggacgaa gtggacaagt tcaaggccaa gttcctgaca gcctggaaca acgtcaagta
      421 cggttgggtg gttaaaagcc ggaccagctt tagcaagatc tccagcatcc acctctgtgg
      481 ccgccgctac cgtttcgagg gcgagggtga catacagcgt ttccagcggg actttgtgtc
      541 ccgcctgtgg ctcacatacc gccgggactt cccgcccctt cctgggggct gcctgacctc
      601 ggactgtggc tgggggtgca tgttacgcag cggccagatg atgctggcac agggccttct
      661 gctgcatttc ctgcccagag actggacatg ggccgagggc atgggcctgg gcccccctga
      721 gctgtcaggg tcagcctctc ccagccggta ccatgggcct gcccgctgga tgcccccacg
      781 ctgggcccag ggtgcccctg agctggagca ggaacgccgg caccggcaga ttgtgtcctg
      841 gttcgccgac cacccccggg ccccctttgg cctacaccgg ctggtggagc ttgggcagag
      901 ctcaggcaag aaggcaggtg actggtatgg gccatcgcta gtggcacaca tcctcaggaa
      961 agccgtggag agctgctccg acgtcacccg cctggtggtg tacgtttctc aggactgcac
     1021 agtgtacaag gcggatgtgg cacgcctggt ggccaggcca gaccccacag ccgagtggaa
     1081 gtctgtggtc atcctggtgc ccgtgcgact gggtggcgag actctcaacc ccgtgtatgt
     1141 gccctgcgtg aaggaactcc tgcgttgcga gctgtgcctg ggcatcatgg gtgggaaacc
     1201 gcgacactca ctgtacttca ttggctacca agatgacttc ctgctgtacc tggaccctca
     1261 ctactgccag cccactgtgg atgtcagcca ggccgacttc cccctggagt ccttccactg
     1321 cacctcgccc cgcaagatgg cctttgccaa gatggaccca agctgtaccg tgggcttcta
     1381 tgctggagac aggaaggagt ttgagacact ctgctcagag ctgaccaggg tcctcagctc
     1441 ctcctcagcc acagagcggt accccatgtt caccctggcc gagggccatg ctcaggacca
     1501 cagcctggac gacctctgct cccagctcgc ccagcccaca ctccggctcc ctcgcacagg
     1561 gcggctcctc agggccaaac gccccagctc tgaggacttt gtgtttttat aaagggaggg
     1621 gatgagggga aagatacaac actatttatt tttttattta tgtcatgtcg ggtgtgggat
     1681 cttgagctct ggcagtgatg atggtacttc ctgttgtcag cccctcaagc ccagctgcaa
     1741 ccagtctggg gccattcagc cagggacaga gcccacagag cccatacacc tgtctcccac
     1801 cagcggggcc ctcctggcag ggtagggaag gaggaccccg ggcacccccc tcagggcctg
     1861 actcacgtac tgtagtttgc actggacgcc cgggccctcc ctgtcccaaa gcccccttgg
     1921 gggaactgtg gctgctgggg gccaataaag ctgtgtaact tga
//
