ATG1_KLUMD
ID ATG1_KLUMD Reviewed; 836 AA.
AC W0T9X4;
DT 25-APR-2018, integrated into UniProtKB/Swiss-Prot.
DT 19-MAR-2014, sequence version 1.
DT 03-AUG-2022, entry version 44.
DE RecName: Full=Serine/threonine-protein kinase ATG1 {ECO:0000305};
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:P53104};
DE AltName: Full=Autophagy-related protein 1 {ECO:0000303|PubMed:26442587};
GN Name=ATG1 {ECO:0000303|PubMed:26442587}; ORFNames=KLMA_30321;
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, 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:4P1N}
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 566-836 IN COMPLEX WITH ATG13,
RP DOMAIN, AND IDENTIFICATION IN THE ATG11-ATG13-ATG17 COMPLEX.
RX PubMed=24793651; DOI=10.1038/nsmb.2822;
RA Fujioka Y., Suzuki S.W., Yamamoto H., Kondo-Kakuta C., Kimura Y.,
RA Hirano H., Akada R., Inagaki F., Ohsumi Y., Noda N.N.;
RT "Structural basis of starvation-induced assembly of the autophagy
RT initiation complex.";
RL Nat. Struct. Mol. Biol. 21:513-521(2014).
CC -!- FUNCTION: Serine/threonine protein kinase involved in the cytoplasm to
CC vacuole transport (Cvt) and found to be essential in autophagy, where
CC it is required for the formation of autophagosomes (By similarity).
CC Involved in the clearance of protein aggregates which cannot be
CC efficiently cleared by the proteasome (By similarity). Required for
CC selective autophagic degradation of the nucleus (nucleophagy) as well
CC as for mitophagy which contributes to regulate mitochondrial quantity
CC and quality by eliminating the mitochondria to a basal level to fulfill
CC cellular energy requirements and preventing excess ROS production (By
CC similarity). Also involved in endoplasmic reticulum-specific autophagic
CC process, in selective removal of ER-associated degradation (ERAD)
CC substrates (By similarity). Plays a key role in ATG9 and ATG23 cycling
CC through the pre-autophagosomal structure and is necessary to promote
CC ATG18 binding to ATG9 through phosphorylation of ATG9. Catalyzes
CC phosphorylation of ATG4, decreasing the interaction between ATG4 and
CC ATG8 and impairing deconjugation of PE-conjugated forms of ATG8 (By
CC similarity). {ECO:0000250|UniProtKB:P53104}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000250|UniProtKB:P53104};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000250|UniProtKB:P53104};
CC -!- SUBUNIT: Homodimer (By similarity). Dimerization requires the presence
CC of ATG13 (By similarity). Forms a ternary complex with ATG13 and ATG17
CC (PubMed:24793651). {ECO:0000250|UniProtKB:P53104,
CC ECO:0000269|PubMed:24793651}.
CC -!- INTERACTION:
CC W0T9X4; W0TA43: ATG13; NbExp=3; IntAct=EBI-16104970, EBI-16104996;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P53104}.
CC Preautophagosomal structure membrane {ECO:0000250|UniProtKB:P53104};
CC Peripheral membrane protein {ECO:0000250|UniProtKB:P53104}.
CC -!- DOMAIN: The LIR motif is required for the interaction with ATG8 and for
CC the association of ATG1 with autophagosomes (By similarity).
CC {ECO:0000250|UniProtKB:P53104}.
CC -!- DOMAIN: The C-terminal region of ATG1 responsible for ATG13-binding
CC comprises six alpha-helices which fold into two antiparallel three-
CC helix bundles resembling each other (PubMed:24793651).
CC {ECO:0000269|PubMed:24793651}.
CC -!- DISRUPTION PHENOTYPE: Still forms preautophagosomal structures (PAS) in
CC proximity to the vacuolar membrane (PubMed:26442587).
CC {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 protein kinase superfamily. Ser/Thr protein
CC kinase family. APG1/unc-51/ULK1 subfamily. {ECO:0000305}.
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DR EMBL; AP012215; BAO39616.1; -; Genomic_DNA.
DR PDB; 4P1N; X-ray; 2.20 A; A/B=564-836.
DR PDBsum; 4P1N; -.
DR AlphaFoldDB; W0T9X4; -.
DR SMR; W0T9X4; -.
DR DIP; DIP-60843N; -.
DR IntAct; W0T9X4; 1.
DR EnsemblFungi; BAO39616; BAO39616; KLMA_30321.
DR OrthoDB; 1084750at2759; -.
DR Proteomes; UP000065495; Chromosome 3.
DR GO; GO:1990316; C:Atg1/ULK1 kinase complex; IEA:EnsemblFungi.
DR GO; GO:0005829; C:cytosol; IEA:EnsemblFungi.
DR GO; GO:0097635; C:extrinsic component of autophagosome membrane; 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:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0000045; P:autophagosome assembly; IEA:EnsemblFungi.
DR GO; GO:0000422; P:autophagy of mitochondrion; 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:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0061709; P:reticulophagy; IEA:EnsemblFungi.
DR InterPro; IPR045269; Atg1-like.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR022708; Ser/Thr_kinase_C.
DR PANTHER; PTHR24348; PTHR24348; 1.
DR Pfam; PF12063; DUF3543; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Autophagy; Cytoplasm; Kinase; Membrane;
KW Nucleotide-binding; Protein transport; Transferase; Transport.
FT CHAIN 1..836
FT /note="Serine/threonine-protein kinase ATG1"
FT /id="PRO_0000443864"
FT DOMAIN 21..321
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 387..425
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 458..489
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 571..836
FT /note="Interaction with ATG13"
FT /evidence="ECO:0000269|PubMed:24793651"
FT REGION 619..642
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 395..425
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 458..486
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 168
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 27..35
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 50
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT HELIX 572..596
FT /evidence="ECO:0007829|PDB:4P1N"
FT HELIX 656..690
FT /evidence="ECO:0007829|PDB:4P1N"
FT HELIX 698..729
FT /evidence="ECO:0007829|PDB:4P1N"
FT HELIX 745..766
FT /evidence="ECO:0007829|PDB:4P1N"
FT HELIX 770..788
FT /evidence="ECO:0007829|PDB:4P1N"
FT STRAND 794..799
FT /evidence="ECO:0007829|PDB:4P1N"
FT STRAND 801..803
FT /evidence="ECO:0007829|PDB:4P1N"
FT HELIX 811..827
FT /evidence="ECO:0007829|PDB:4P1N"
FT HELIX 829..834
FT /evidence="ECO:0007829|PDB:4P1N"
SQ SEQUENCE 836 AA; 94266 MW; 7CB20B36C4869FB4 CRC64;
MSSESHGKAV AKAIRLPTEN YTVEKEIGKG SFAIVYKGVS LRDGRNIAIK AVSRSKLKNK
KLLENLEVEI AILKKIKHPH IVGLIDCERT STDFYLIMEY CALGDLTFFI KKRRSLVMKH
PLIKTVFDLY PPPSAEHNGL NRVLVVNYLQ QLSSALKFLR SKNLVHRDIK PQNLLLCTPL
QDYSDPKTFH EMGFIGIYNL PVLKIADFGF ARFLPNTSLA ETLCGSPLYM APEILNYQKY
NAKADLWSVG TVLYEMCCGR PPFKASNHLE LFQKIKKAND EVTVPSNCYI EPKIFKLIKG
LLTFDPEARM GFNEFFNNEV VTEDLSRYEA SYEPDLESKS KDVAESNMFV SEYLVRPAAQ
EKANGGLRTD EGSAMPGAEH TYNKEREHYR ERQDLQGQQQ QQQQHPDSPP RGSTQGYQSS
AGQTRMKSSY NDLILEKEYV VVEKKTVEVN SLADDFANNG PTTNNQGAQI IKPLRYRTSS
SSDGHGGRRA SLVERRLSIS SLSPSNALSK ALGLASVRLF GYQQPNTQTT STSTHPTLLN
PQIFHELTEN AVLRADHHLN LFNEQISDSN ITPFVESLSA KAFVMYSFAE MKFSQILPSP
PSSTDYYSQS DKRLSNGSCA IDDDDDLDSG NPSSNQTLTP GANKVSAANV DNLIPAPELK
KLCMESLLLY LKSLTILASS MKLTSKWWYE NESKNCTLKL NILVQWIRDR FNECLDKAEF
LRLKLHTLNQ SEDPQVLDDE PTIFVEKLIY DRALDISRNA ARLEMEGGNY NTCELAYATS
LWMLEILLDE HLSSNEVYDD GYSSNITSLD ESDKEMIRKY VSSIANRLKA LKSKMS
