ATG5_KLUMD
ID ATG5_KLUMD Reviewed; 271 AA.
AC W0T4V8; J3QW33;
DT 25-APR-2018, integrated into UniProtKB/Swiss-Prot.
DT 19-MAR-2014, sequence version 1.
DT 25-MAY-2022, entry version 26.
DE RecName: Full=Autophagy-related protein 5 {ECO:0000303|PubMed:26442587};
GN Name=ATG5 {ECO:0000303|PubMed:26442587}; ORFNames=KLMA_20199;
OS Kluyveromyces marxianus (strain DMKU3-1042 / BCC 29191 / NBRC 104275)
OS (Yeast) (Candida kefyr).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Kluyveromyces.
OX NCBI_TaxID=1003335;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=DMKU3-1042 / BCC 29191 / NBRC 104275;
RX PubMed=25834639; DOI=10.1186/s13068-015-0227-x;
RA Lertwattanasakul N., Kosaka T., Hosoyama A., Suzuki Y., Rodrussamee N.,
RA Matsutani M., Murata M., Fujimoto N., Suprayogi X., Tsuchikane K.,
RA Limtong S., Fujita N., Yamada M.;
RT "Genetic basis of the highly efficient yeast Kluyveromyces marxianus:
RT complete genome sequence and transcriptome analyses.";
RL Biotechnol. Biofuels 8:47-47(2015).
RN [2]
RP IDENTIFICATION, FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=26442587; DOI=10.1074/jbc.m115.684233;
RA Yamamoto H., Shima T., Yamaguchi M., Mochizuki Y., Hoshida H., Kakuta S.,
RA Kondo-Kakuta C., Noda N.N., Inagaki F., Itoh T., Akada R., Ohsumi Y.;
RT "The thermotolerant yeast Kluyveromyces marxianus is a useful organism for
RT structural and biochemical studies of autophagy.";
RL J. Biol. Chem. 290:29506-29518(2015).
RN [3] {ECO:0007744|PDB:3VQI}
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS), INTERACTION WITH ATG10 AND ATG12,
RP FUNCTION, AND MUTAGENESIS OF LEU-127; LYS-145; VAL-208 AND GLN-210.
RX PubMed=22682742; DOI=10.1016/j.str.2012.04.018;
RA Yamaguchi M., Noda N.N., Yamamoto H., Shima T., Kumeta H., Kobashigawa Y.,
RA Akada R., Ohsumi Y., Inagaki F.;
RT "Structural insights into Atg10-mediated formation of the autophagy-
RT essential Atg12-Atg5 conjugate.";
RL Structure 20:1244-1254(2012).
CC -!- FUNCTION: Involved in cytoplasm to vacuole transport (Cvt) and
CC autophagic vesicle formation (PubMed:26442587). Autophagy is essential
CC for maintenance of amino acid levels and protein synthesis under
CC nitrogen starvation (By similarity). Required for selective autophagic
CC degradation of the nucleus (nucleophagy) (By similarity). Also required
CC for mitophagy, which eliminates defective or superfluous mitochondria
CC in order to fulfill cellular energy requirements and prevent excess ROS
CC production (By similarity). Conjugation with ATG12, through a
CC ubiquitin-like conjugating system involving ATG7 as an E1-like
CC activating enzyme and ATG10 as an E2-like conjugating enzyme, is
CC essential for its function (PubMed:22682742). The ATG12-ATG5 conjugate
CC acts as an E3-like enzyme which is required for lipidation of ATG8 and
CC ATG8 association to the vesicle membranes (By similarity). ATG12-ATG5
CC rearranges the ATG3 catalytic center and enhances its E2 activity (By
CC similarity). {ECO:0000250|UniProtKB:Q12380,
CC ECO:0000269|PubMed:22682742, ECO:0000269|PubMed:26442587}.
CC -!- SUBUNIT: Conjugated with ATG12 (PubMed:22682742). Interacts with ATG10
CC (PubMed:22682742). The ATG5-ATG12 conjugate forms a complex with
CC several units of ATG16 (By similarity). The ATG12-ATG5 conjugate
CC associates also with ATG3 (By similarity).
CC {ECO:0000250|UniProtKB:Q12380, ECO:0000269|PubMed:22682742}.
CC -!- SUBCELLULAR LOCATION: Preautophagosomal structure membrane
CC {ECO:0000250|UniProtKB:Q12380}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q12380}. Note=Localizes to the isolation
CC membrane (IM), a membrane sac which is generated from the pre-
CC autophagosomal structure (PAS) (By similarity). Ultimately, the IM
CC expands to become a mature autophagosome (By similarity). Localizes
CC also to a dot at the junction between the IM and the vacuolar membrane,
CC termed the vacuole-IM contact site (VICS) (By similarity). Correct
CC localization to the PAS requires ATG21 (By similarity).
CC {ECO:0000250|UniProtKB:Q12380}.
CC -!- PTM: Conjugated to ATG12; which is essential for autophagy
CC (PubMed:22682742). Conjugation with ATG12 involves ATG7 as an E1-like
CC activating enzyme and ATG10 as an E2-like conjugating enzyme (By
CC similarity). {ECO:0000250|UniProtKB:Q12380,
CC ECO:0000269|PubMed:22682742}.
CC -!- DISRUPTION PHENOTYPE: Impairs the formation of preautophagosomal
CC structures (PubMed:26442587). {ECO:0000269|PubMed:26442587}.
CC -!- MISCELLANEOUS: Kluyveromyces marxianus proteins are shorter in length
CC and have a more ordered secondary structure than their S.cerevisiae
CC counterparts, which might contribute to the superior thermotolerance
CC and solubility (PubMed:26442587). K.marxianus could be therefore useful
CC as a new model organism for further elucidation of the molecular
CC details of autophagy (PubMed:26442587). {ECO:0000269|PubMed:26442587}.
CC -!- SIMILARITY: Belongs to the ATG5 family. {ECO:0000305}.
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DR EMBL; AP012214; BAO38657.1; -; Genomic_DNA.
DR PDB; 3VQI; X-ray; 2.50 A; A/B/C/D/E=1-271.
DR PDBsum; 3VQI; -.
DR AlphaFoldDB; W0T4V8; -.
DR SMR; W0T4V8; -.
DR EnsemblFungi; BAO38657; BAO38657; KLMA_20199.
DR OrthoDB; 457861at2759; -.
DR Proteomes; UP000065495; Chromosome 2.
DR GO; GO:0034274; C:Atg12-Atg5-Atg16 complex; IEA:EnsemblFungi.
DR GO; GO:0005776; C:autophagosome; IEA:EnsemblFungi.
DR GO; GO:0005829; C:cytosol; IEA:EnsemblFungi.
DR GO; GO:0061908; C:phagophore; IEA:EnsemblFungi.
DR GO; GO:0034045; C:phagophore assembly site membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0120095; C:vacuole-isolation membrane contact site; IEA:EnsemblFungi.
DR GO; GO:0019776; F:Atg8 ligase activity; IEA:EnsemblFungi.
DR GO; GO:0140355; F:cargo receptor ligand activity; IEA:EnsemblFungi.
DR GO; GO:0008047; F:enzyme activator activity; IEA:EnsemblFungi.
DR GO; GO:0000422; P:autophagy of mitochondrion; IEA:EnsemblFungi.
DR GO; GO:0006501; P:C-terminal protein lipidation; IEA:EnsemblFungi.
DR GO; GO:0032258; P:cytoplasm to vacuole transport by the Cvt pathway; IEA:EnsemblFungi.
DR GO; GO:0044805; P:late nucleophagy; IEA:EnsemblFungi.
DR GO; GO:0034727; P:piecemeal microautophagy of the nucleus; IEA:EnsemblFungi.
DR GO; GO:0061912; P:selective autophagy; IEA:EnsemblFungi.
DR Gene3D; 1.10.246.190; -; 1.
DR Gene3D; 3.10.20.620; -; 1.
DR InterPro; IPR007239; Atg5.
DR InterPro; IPR042526; Atg5_HR.
DR InterPro; IPR042527; Atg5_UblA_dom.
DR PANTHER; PTHR13040; PTHR13040; 1.
DR Pfam; PF04106; APG5; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Autophagy; Isopeptide bond; Membrane; Protein transport;
KW Transport; Ubl conjugation.
FT CHAIN 1..271
FT /note="Autophagy-related protein 5"
FT /id="PRO_0000443876"
FT CROSSLNK 145
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ATG12)"
FT /evidence="ECO:0000269|PubMed:22682742"
FT MUTAGEN 127
FT /note="L->A: Reduces the formation of the ATG12-ATG5
FT conjugate."
FT /evidence="ECO:0000269|PubMed:22682742"
FT MUTAGEN 145
FT /note="K->A: Impairs the formation of the ATG12-ATG5
FT conjugate."
FT /evidence="ECO:0000269|PubMed:22682742"
FT MUTAGEN 208
FT /note="V->A: Reduces the formation of the ATG12-ATG5
FT conjugate."
FT /evidence="ECO:0000269|PubMed:22682742"
FT MUTAGEN 210
FT /note="Q->A: Reduces the formation of the ATG12-ATG5
FT conjugate."
FT /evidence="ECO:0000269|PubMed:22682742"
FT HELIX 3..9
FT /evidence="ECO:0007829|PDB:3VQI"
FT STRAND 12..19
FT /evidence="ECO:0007829|PDB:3VQI"
FT TURN 21..23
FT /evidence="ECO:0007829|PDB:3VQI"
FT HELIX 31..33
FT /evidence="ECO:0007829|PDB:3VQI"
FT STRAND 34..40
FT /evidence="ECO:0007829|PDB:3VQI"
FT HELIX 45..56
FT /evidence="ECO:0007829|PDB:3VQI"
FT HELIX 57..59
FT /evidence="ECO:0007829|PDB:3VQI"
FT STRAND 71..75
FT /evidence="ECO:0007829|PDB:3VQI"
FT HELIX 86..93
FT /evidence="ECO:0007829|PDB:3VQI"
FT STRAND 111..118
FT /evidence="ECO:0007829|PDB:3VQI"
FT HELIX 132..152
FT /evidence="ECO:0007829|PDB:3VQI"
FT STRAND 153..155
FT /evidence="ECO:0007829|PDB:3VQI"
FT TURN 157..160
FT /evidence="ECO:0007829|PDB:3VQI"
FT HELIX 163..175
FT /evidence="ECO:0007829|PDB:3VQI"
FT HELIX 178..186
FT /evidence="ECO:0007829|PDB:3VQI"
FT HELIX 191..193
FT /evidence="ECO:0007829|PDB:3VQI"
FT STRAND 199..202
FT /evidence="ECO:0007829|PDB:3VQI"
FT HELIX 222..227
FT /evidence="ECO:0007829|PDB:3VQI"
FT TURN 228..230
FT /evidence="ECO:0007829|PDB:3VQI"
FT STRAND 238..241
FT /evidence="ECO:0007829|PDB:3VQI"
FT STRAND 244..247
FT /evidence="ECO:0007829|PDB:3VQI"
FT HELIX 252..259
FT /evidence="ECO:0007829|PDB:3VQI"
FT STRAND 266..269
FT /evidence="ECO:0007829|PDB:3VQI"
SQ SEQUENCE 271 AA; 31242 MW; CBB29B25D24B9A02 CRC64;
MEELRERVWN GTINVEVVVS DAIVVPNTTL ADKSCHIVML RDAYLGFYLP TVVRKLADTI
KVPYESDYRN WWFEYNGEGV PWEYPCGVLF DLLNKKRKKQ GNELDDTSLQ MWELQLCHGD
KYPRGILPLV DGHSQIKDYW RHQWKQACFI LNGSAKRIMS LSIPDFENFW VSILSRNRSD
FMAVRSKLFS MNKAKSLPVR VWTSNYAVLQ PTVPVTDKEL SVAELLDSIK LSSDGVKSVI
IQGIDVSIED NIFELYDIFA SIDGFLYLVT K
