ATG9A_PONAB
ID ATG9A_PONAB Reviewed; 839 AA.
AC Q5RCS0;
DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 75.
DE RecName: Full=Autophagy-related protein 9A {ECO:0000305};
DE AltName: Full=APG9-like 1 {ECO:0000250|UniProtKB:Q7Z3C6};
GN Name=ATG9A {ECO:0000250|UniProtKB:Q7Z3C6};
GN Synonyms=APG9L1 {ECO:0000250|UniProtKB:Q7Z3C6};
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain cortex;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Phospholipid scramblase involved in autophagy by mediating
CC autophagosomal membrane expansion. Cycles between the preautophagosomal
CC structure/phagophore assembly site (PAS) and the cytoplasmic vesicle
CC pool and supplies membrane for the growing autophagosome. Lipid
CC scramblase activity plays a key role in preautophagosomal
CC structure/phagophore assembly by distributing the phospholipids that
CC arrive through ATG2 (ATG2A or ATG2B) from the cytoplasmic to the
CC luminal leaflet of the bilayer, thereby driving autophagosomal membrane
CC expansion. Also required to supply phosphatidylinositol 4-phosphate to
CC the autophagosome initiation site by recruiting the
CC phosphatidylinositol 4-kinase beta (PI4KB) in a process dependent on
CC ARFIP2, but not ARFIP1 (By similarity). In addition to autophagy, also
CC plays a role in necrotic cell death (By similarity).
CC {ECO:0000250|UniProtKB:Q68FE2, ECO:0000250|UniProtKB:Q7Z3C6}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine(in) = a 1,2-diacyl-
CC sn-glycero-3-phosphocholine(out); Xref=Rhea:RHEA:38571,
CC ChEBI:CHEBI:57643; Evidence={ECO:0000250|UniProtKB:Q7Z3C6};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-L-serine(in) = a 1,2-diacyl-
CC sn-glycero-3-phospho-L-serine(out); Xref=Rhea:RHEA:38663,
CC ChEBI:CHEBI:57262; Evidence={ECO:0000250|UniProtKB:Q7Z3C6};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphoethanolamine(in) = a 1,2-
CC diacyl-sn-glycero-3-phosphoethanolamine(out); Xref=Rhea:RHEA:38895,
CC ChEBI:CHEBI:64612; Evidence={ECO:0000250|UniProtKB:Q7Z3C6};
CC -!- SUBUNIT: Homotrimer; forms a homotrimer with a central pore that forms
CC a path between the two membrane leaflets. Interacts (via cytoplasmic
CC its C-terminus) with ATG2A. Interacts with SUPT20H. Interacts (via the
CC tyrosine-based sorting signal motif) with AP4M1; promoting association
CC with the AP-4 complex. Interacts with ARFIP1 and ARFIP2. Interacts with
CC PI4K2A and PI4KB. Interacts with ATG4A; the interaction is direct and
CC promotes ATG9A trafficking. {ECO:0000250|UniProtKB:Q7Z3C6}.
CC -!- SUBCELLULAR LOCATION: Preautophagosomal structure membrane
CC {ECO:0000250|UniProtKB:Q7Z3C6}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q7Z3C6}. Cytoplasmic vesicle, autophagosome
CC membrane {ECO:0000250|UniProtKB:Q7Z3C6}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q7Z3C6}. Golgi apparatus, trans-Golgi network
CC membrane {ECO:0000250|UniProtKB:Q7Z3C6}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q7Z3C6}. Late endosome membrane
CC {ECO:0000250|UniProtKB:Q7Z3C6}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q7Z3C6}. Recycling endosome membrane
CC {ECO:0000250|UniProtKB:Q7Z3C6}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q7Z3C6}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q7Z3C6}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q7Z3C6}. Mitochondrion membrane
CC {ECO:0000250|UniProtKB:Q7Z3C6}; Multi-pass membrane protein
CC {ECO:0000255}. Note=Mainly localizes to the trans-Golgi network (TGN)
CC and the endosomal system; cycles between them though vesicle
CC trafficking. Export from the TGN to promote formation of autophagosomes
CC is mediated by the AP-4 complex. Under amino acid starvation or
CC rapamycin treatment, redistributes to preautophagosomal
CC structure/phagophore assembly site (PAS). The starvation-induced
CC redistribution depends on ULK1, ATG13, as well as SH3GLB1. Upon
CC autophagy induction, a small portion transiently localizes to the
CC autophagic membranes. Recruited to damaged mitochondria during
CC mitophagy in a RIMOC1-dependent manner. {ECO:0000250|UniProtKB:Q7Z3C6}.
CC -!- DOMAIN: Forms a homotrimer with a solvated central pore, which is
CC connected laterally to the cytosol through the cavity within each
CC protomer. Acts as a lipid scramblase that uses its central pore to
CC function: the central pore opens laterally to accommodate lipid
CC headgroups, thereby enabling lipid flipping and redistribution of
CC lipids added to the outer leaflet of ATG9A-containing vesicles, thereby
CC enabling growth into autophagosomes. {ECO:0000250|UniProtKB:Q7Z3C6}.
CC -!- DOMAIN: The tyrosine-based sorting signal motif, also named YXX-psi
CC motif, promotes interaction with the AP-4 complex.
CC {ECO:0000250|UniProtKB:Q7Z3C6}.
CC -!- SIMILARITY: Belongs to the ATG9 family. {ECO:0000305}.
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; CR858199; CAH90437.1; -; mRNA.
DR RefSeq; NP_001127287.1; NM_001133815.1.
DR RefSeq; XP_009236371.1; XM_009238096.1.
DR RefSeq; XP_009236372.1; XM_009238097.1.
DR AlphaFoldDB; Q5RCS0; -.
DR SMR; Q5RCS0; -.
DR STRING; 9601.ENSPPYP00000014748; -.
DR Ensembl; ENSPPYT00000015345; ENSPPYP00000014748; ENSPPYG00000013199.
DR GeneID; 100174344; -.
DR KEGG; pon:100174344; -.
DR CTD; 79065; -.
DR eggNOG; KOG2173; Eukaryota.
DR GeneTree; ENSGT00390000014839; -.
DR InParanoid; Q5RCS0; -.
DR OrthoDB; 712239at2759; -.
DR Proteomes; UP000001595; Chromosome 2B.
DR GO; GO:0000421; C:autophagosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0031966; C:mitochondrial membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0034045; C:phagophore assembly site membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0055038; C:recycling endosome membrane; ISS:UniProtKB.
DR GO; GO:0005802; C:trans-Golgi network; ISS:UniProtKB.
DR GO; GO:0017128; F:phospholipid scramblase activity; ISS:UniProtKB.
DR GO; GO:0000045; P:autophagosome assembly; ISS:UniProtKB.
DR GO; GO:0060349; P:bone morphogenesis; ISS:UniProtKB.
DR GO; GO:0010940; P:positive regulation of necrotic cell death; ISS:UniProtKB.
DR InterPro; IPR007241; Autophagy-rel_prot_9.
DR PANTHER; PTHR13038; PTHR13038; 1.
DR Pfam; PF04109; ATG9; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Autophagy; Cytoplasmic vesicle; Endoplasmic reticulum;
KW Endosome; Glycoprotein; Golgi apparatus; Lipid transport; Membrane;
KW Mitochondrion; Phosphoprotein; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q7Z3C6"
FT CHAIN 2..839
FT /note="Autophagy-related protein 9A"
FT /id="PRO_0000119822"
FT TOPO_DOM 2..61
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 62..84
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q7Z3C6"
FT TOPO_DOM 85..128
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 129..154
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q7Z3C6"
FT TOPO_DOM 155..290
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT INTRAMEM 291..301
FT /evidence="ECO:0000250|UniProtKB:Q7Z3C6"
FT TOPO_DOM 302..319
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT INTRAMEM 320..328
FT /evidence="ECO:0000250|UniProtKB:Q7Z3C6"
FT TOPO_DOM 329..371
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 372..397
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q7Z3C6"
FT TOPO_DOM 398..406
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 407..424
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q7Z3C6"
FT TOPO_DOM 425..470
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT INTRAMEM 471..480
FT /evidence="ECO:0000250|UniProtKB:Q7Z3C6"
FT TOPO_DOM 481..483
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT INTRAMEM 484..492
FT /evidence="ECO:0000250|UniProtKB:Q7Z3C6"
FT TOPO_DOM 493..839
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 656..686
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 719..839
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 8..11
FT /note="Tyrosine-based sorting signal"
FT /evidence="ECO:0000250|UniProtKB:Q7Z3C6"
FT COMPBIAS 720..740
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 818..839
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z3C6"
FT MOD_RES 14
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z3C6"
FT MOD_RES 16
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q68FE2"
FT MOD_RES 18
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z3C6"
FT MOD_RES 656
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z3C6"
FT MOD_RES 735
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z3C6"
FT MOD_RES 738
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z3C6"
FT MOD_RES 741
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z3C6"
FT MOD_RES 828
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z3C6"
FT CARBOHYD 99
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 839 AA; 94433 MW; D408C0B38877A163 CRC64;
MAQFDTEYQR LEASYSDSPP GEEDLLVHVA EGSKSPWHHI ENLDLFFSRV YNLHQKNGFT
CMLIGEIFEL MQFLFVVAFT TFLVSCVDYD ILFANKMVNH SLHPTEPVKV TLPDAFLPAQ
VCSARIQENG SLITILVIAG VFWIHRLIKF IYNICCYWEI HSFYLHALRI PMSALPYCTW
QEVQARIVQT QKEHQICIHK RELTELDIYH RILRFQNYMV ALVNKSLLPL RFRLPGLGEA
VFFTRGLKYN FELILFWGPG SLFLNEWSLK AEYKRGGQRL ELAQRLSNRI LWIGIANFLL
CPLILIWQIL YAFFSYAEVL KREPGALGAR CWSLYGRCYL RHFNELEHEL QSRLNRGYKP
ASKYMNCFLS PLLTLLAKNG AFFAGSILAV LIALTIYDED VLAVEHVLTT VTLLGVTVTV
CRSFIPDQHM VFCPEQLLRV ILAHIHYMPD HWQGNAHRSQ TRDEFAQLFQ YKAVFILEEL
LSPIVTPLIL IFCLRPRALE IIDFFRNFTV EVVGVGDTCS FAQMDVRQHG HPQWLSAGQT
EASVYQQAED GKTELSLMHF AITNPGWQPP RESTAFLGFL KEQVQRDGAA ASLAQGGLLP
ENALFTSIQS LQSESEPLSL IANVVAGSSC RGPPLPRDLQ GSRHRAEVAS ALRSFSPLQP
GQAPTGRAHS TMTGSGVDAR TASSGSSVWE GQLQSLVLSE YASTEMSLHA LYMHQLHKQQ
AQAEPERHLW HRRESDESGE SAPDEGGEGA RAPQSIPRSA SYPCAAPRPG APETTALHGG
FQRRYGGITD PGTVPRAPSH FSRLPLGGWA EDGQSASRHP EPVPEEGSED ELPPQVHKV
