A16L1_PONAB
ID A16L1_PONAB Reviewed; 607 AA.
AC Q5RAC9;
DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 25-MAY-2022, entry version 95.
DE RecName: Full=Autophagy-related protein 16-1;
DE AltName: Full=APG16-like 1;
GN Name=ATG16L1; Synonyms=APG16L;
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=Kidney;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Plays an essential role in both canonical and non-canonical
CC autophagy: interacts with ATG12-ATG5 to mediate the lipidation to ATG8
CC family proteins (MAP1LC3A, MAP1LC3B, MAP1LC3C, GABARAPL1, GABARAPL2 and
CC GABARAP). Acts as a molecular hub, coordinating autophagy pathways via
CC distinct domains that support either canonical or non-canonical
CC signaling. During canonical autophagy, interacts with ATG12-ATG5 to
CC mediate the conjugation of phosphatidylethanolamine (PE) to ATG8
CC proteins, to produce a membrane-bound activated form of ATG8. Thereby,
CC controls the elongation of the nascent autophagosomal membrane. Also
CC involved in non-canonical autophagy, a parallel pathway involving
CC conjugation of ATG8 proteins to single membranes at endolysosomal
CC compartments, probably by catalyzing conjugation of phosphatidylserine
CC (PS) to ATG8 (By similarity). Non-canonical autophagy plays a key role
CC in epithelial cells to limit lethal infection by influenza A (IAV)
CC virus (By similarity). Regulates mitochondrial antiviral signaling
CC (MAVS)-dependent type I interferon (IFN-I) production. Negatively
CC regulates NOD1- and NOD2-driven inflammatory cytokine response.
CC Instead, promotes with NOD2 an autophagy-dependent antibacterial
CC pathway. Plays a role in regulating morphology and function of Paneth
CC cell (By similarity). {ECO:0000250|UniProtKB:Q676U5,
CC ECO:0000250|UniProtKB:Q8C0J2}.
CC -!- SUBUNIT: Homodimer (By similarity). Homooligomer (By similarity).
CC Heterooligomer with ATG16L2 (By similarity). Interacts with WIPI1.
CC Interacts with WIPI2. Interacts with RB1CC1; the interaction is
CC required for ULK1 complex-dependent autophagy. Interacts with ATG5.
CC Part of either the minor and major complexes respectively composed of 4
CC sets of ATG12-ATG5 and ATG16L1 (400 kDa) or 8 sets of ATG12-ATG5 and
CC ATG16L1 (800 kDa). Interacts with RAB33B. Interacts (via WD repeats)
CC with TMEM59; the interaction mediates unconventional autophagic
CC activity of TMEM59. Interacts with TLR2 and NOD2. Interacts (via WD
CC repeats) with MEFV. Interacts with PPP1CA; the interaction
CC dephosphorylates ATG16L1 causing dissociation of ATG12-ATG5-ATG16L1
CC complex. Interacts (via N-terminal) with CLTC. Interacts with NOD2.
CC Interacts with TUFM. Interacts with TRIM16 (By similarity). Interacts
CC (via WD repeats) with SPATA33 (By similarity).
CC {ECO:0000250|UniProtKB:Q676U5, ECO:0000250|UniProtKB:Q8C0J2}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q676U5}.
CC Preautophagosomal structure membrane {ECO:0000250|UniProtKB:Q676U5};
CC Peripheral membrane protein {ECO:0000305}. Endosome membrane
CC {ECO:0000250|UniProtKB:Q676U5}; Peripheral membrane protein
CC {ECO:0000305}. Lysosome membrane {ECO:0000305}; Peripheral membrane
CC protein {ECO:0000250|UniProtKB:Q676U5}. Note=Recruited to omegasomes
CC membranes by WIPI2. Omegasomes are endoplasmic reticulum connected
CC strutures at the origin of preautophagosomal structures. Localized to
CC preautophagosomal structure (PAS) where it is involved in the membrane
CC targeting of ATG5. Localizes also to discrete punctae along the ciliary
CC axoneme (By similarity). Upon activation of non-canonical autophagy,
CC recruited to single-membrane endolysosomal compartments (By
CC similarity). {ECO:0000250|UniProtKB:Q676U5,
CC ECO:0000250|UniProtKB:Q8C0J2}.
CC -!- DOMAIN: The WD repeats are required for non-canonical autophagy but not
CC for canonical autophagy. {ECO:0000250|UniProtKB:Q676U5}.
CC -!- PTM: Proteolytic cleavage by activated CASP3 leads to degradation and
CC may regulate autophagy upon cellular stress and apoptotic stimuli.
CC {ECO:0000250|UniProtKB:Q676U5}.
CC -!- PTM: Phosphorylation at Ser-139 promotes association with the ATG12-
CC ATG5 conjugate to form the ATG12-ATG5-ATG16L1 complex.
CC {ECO:0000250|UniProtKB:Q676U5}.
CC -!- SIMILARITY: Belongs to the WD repeat ATG16 family. {ECO:0000305}.
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DR EMBL; CR859089; CAH91281.1; -; mRNA.
DR RefSeq; NP_001125757.1; NM_001132285.2.
DR AlphaFoldDB; Q5RAC9; -.
DR SMR; Q5RAC9; -.
DR STRING; 9601.ENSPPYP00000014856; -.
DR GeneID; 100172682; -.
DR KEGG; pon:100172682; -.
DR CTD; 55054; -.
DR eggNOG; KOG0288; Eukaryota.
DR InParanoid; Q5RAC9; -.
DR OrthoDB; 404224at2759; -.
DR Proteomes; UP000001595; Unplaced.
DR GO; GO:0034274; C:Atg12-Atg5-Atg16 complex; ISS:UniProtKB.
DR GO; GO:0000421; C:autophagosome membrane; ISS:UniProtKB.
DR GO; GO:0005930; C:axoneme; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0036020; C:endolysosome membrane; ISS:UniProtKB.
DR GO; GO:0034045; C:phagophore assembly site membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0097225; C:sperm midpiece; ISS:UniProtKB.
DR GO; GO:0120095; C:vacuole-isolation membrane contact site; ISS:UniProtKB.
DR GO; GO:0000045; P:autophagosome assembly; IEA:InterPro.
DR GO; GO:0006501; P:C-terminal protein lipidation; ISS:UniProtKB.
DR GO; GO:0016237; P:lysosomal microautophagy; ISS:UniProtKB.
DR GO; GO:0016236; P:macroautophagy; ISS:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR Gene3D; 2.130.10.10; -; 2.
DR InterPro; IPR045160; ATG16.
DR InterPro; IPR013923; Autophagy-rel_prot_16_dom.
DR InterPro; IPR020472; G-protein_beta_WD-40_rep.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR019775; WD40_repeat_CS.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR PANTHER; PTHR19878; PTHR19878; 1.
DR Pfam; PF08614; ATG16; 1.
DR Pfam; PF00400; WD40; 4.
DR PRINTS; PR00320; GPROTEINBRPT.
DR SMART; SM00320; WD40; 7.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 2.
DR PROSITE; PS50082; WD_REPEATS_2; 5.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 2: Evidence at transcript level;
KW Autophagy; Coiled coil; Cytoplasm; Endosome; Lysosome; Membrane;
KW Phosphoprotein; Protein transport; Reference proteome; Repeat; Transport;
KW WD repeat.
FT CHAIN 1..607
FT /note="Autophagy-related protein 16-1"
FT /id="PRO_0000050850"
FT REPEAT 320..359
FT /note="WD 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00221"
FT REPEAT 364..403
FT /note="WD 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00221"
FT REPEAT 406..445
FT /note="WD 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00221"
FT REPEAT 447..484
FT /note="WD 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00221"
FT REPEAT 486..525
FT /note="WD 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00221"
FT REPEAT 532..573
FT /note="WD 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00221"
FT REPEAT 575..607
FT /note="WD 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00221"
FT REGION 13..43
FT /note="Interaction with ATG5"
FT /evidence="ECO:0000250|UniProtKB:Q676U5"
FT REGION 207..230
FT /note="WIPI2-binding"
FT /evidence="ECO:0000250|UniProtKB:Q676U5"
FT REGION 230..242
FT /note="RB1CC1-binding"
FT /evidence="ECO:0000250|UniProtKB:Q676U5"
FT COILED 79..230
FT /evidence="ECO:0000255"
FT MOTIF 296..299
FT /note="Caspase cleavage"
FT MOD_RES 139
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q676U5"
FT MOD_RES 269
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q676U5"
FT MOD_RES 287
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q676U5"
SQ SEQUENCE 607 AA; 68230 MW; F0951C0720F2B213 CRC64;
MSSGLRAADF PRWKRHISEQ LRRRDRLQRQ AFEEIILQYN KLLEKSDLHS VLAQKLQAEK
HDVPNRHEIS PGHDGTWNDS QLQEMAQLRI KHQEELTELH KKRGELAQLV IDLNNQMQRK
DREMQMNEAK IAECLQTISD LETECLDLRT KLCDLERANQ TLKDEYDALQ ITFTALEGKL
RKTTEENQEL VTRWMAEKAQ EANRLNAENE KDSRRRQARL QKELAEAAKE PLPVEQDDDI
EVIVDETSDH TEETSPVRAI SRAATKRLSQ PAGGLLDSIT NIFGRRSVSS FPVPQDNVDT
HPGSGKEVRV PTTALCVFDA HDGEVNAVQF SPGSRLLATG GMDRRVKLWE VFGEKCEFKG
SLSGSNAGIT SIEFDSAGSY LLAASNDFAS RIWTVDDSRL RHTLTGHSGK VLSAKFLLDN
ARIVSGSHDR TLKHWDLRSK VCIKTVFAGS SCNDIVCTEQ CVMSGHFDKK IRFWDIRSES
IVREMELLGK ITALDLNPER TELLSCSRDD LLKVIDLRTN AIKQTFSAPG FKCGSDWTRV
VFSPDGSYVA AGSAEGSLYT WSVLTGKVEK VLSKQHSSSI NAVAWSPSGL HVVSVDKGCK
AVLWAQY
