ID ATG9B_HUMAN Reviewed; 924 AA. AC Q674R7; A1A5D3; Q6JRW5; Q8N8I8; DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot. DT 11-OCT-2004, sequence version 1. DT 29-SEP-2021, entry version 123. DE RecName: Full=Autophagy-related protein 9B {ECO:0000305}; DE AltName: Full=APG9-like 2 {ECO:0000303|PubMed:15755735}; DE AltName: Full=Nitric oxide synthase 3-overlapping antisense gene protein {ECO:0000303|PubMed:15234981}; DE Short=Protein sONE {ECO:0000303|PubMed:15234981}; GN Name=ATG9B; GN Synonyms=APG9L2 {ECO:0000303|PubMed:15755735}, GN NOS3AS {ECO:0000303|PubMed:15234981}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY. RC TISSUE=Testis; RX PubMed=15234981; DOI=10.1074/jbc.m400271200; RA Robb G.B., Carson A.R., Tai S.C., Fish J.E., Singh S., Yamada T., RA Scherer S.W., Nakabayashi K., Marsden P.A.; RT "Post-transcriptional regulation of endothelial nitric-oxide synthase by an RT overlapping antisense mRNA transcript."; RL J. Biol. Chem. 279:37982-37996(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Placenta; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H., RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., RA Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [4] RP IDENTIFICATION. RX PubMed=15755735; DOI=10.1074/jbc.m413957200; RA Yamada T., Carson A.R., Caniggia I., Umebayashi K., Yoshimori T., RA Nakabayashi K., Scherer S.W.; RT "Endothelial nitric-oxide synthase antisense (NOS3AS) gene encodes an RT autophagy-related protein (APG9-like2) highly expressed in trophoblast."; RL J. Biol. Chem. 280:18283-18290(2005). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP INDUCTION. RX PubMed=17403686; DOI=10.1074/jbc.m608318200; RA Fish J.E., Matouk C.C., Yeboah E., Bevan S.C., Khan M., Patil K., Ohh M., RA Marsden P.A.; RT "Hypoxia-inducible expression of a natural cis-antisense transcript RT inhibits endothelial nitric-oxide synthase."; RL J. Biol. Chem. 282:15652-15666(2007). RN [7] RP SUBCELLULAR LOCATION. RX PubMed=18936157; DOI=10.1128/mcb.01082-08; RA Chan E.Y.W., Longatti A., McKnight N.C., Tooze S.A.; RT "Kinase-inactivated ULK proteins inhibit autophagy via their conserved C- RT terminal domains using an Atg13-independent mechanism."; RL Mol. Cell. Biol. 29:157-171(2009). 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 (By similarity). In addition to autophagy, also plays a role CC in necrotic cell death (By similarity). {ECO:0000250|UniProtKB:Q68FE2, CC 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. CC {ECO:0000250|UniProtKB:Q7Z3C6}. CC -!- INTERACTION: CC Q674R7-2; P49639: HOXA1; NbExp=3; IntAct=EBI-12837280, EBI-740785; CC Q674R7-2; P32242: OTX1; NbExp=3; IntAct=EBI-12837280, EBI-740446; CC -!- SUBCELLULAR LOCATION: Preautophagosomal structure membrane CC {ECO:0000269|PubMed:18936157}; Multi-pass membrane protein CC {ECO:0000269|PubMed:18936157}. Note=Under amino acid starvation or CC rapamycin treatment, redistributes from a juxtanuclear clustered pool CC to a dispersed peripheral cytosolic pool (PubMed:18936157). The CC starvation-induced redistribution depends on ULK1 and ATG13 CC (PubMed:18936157). {ECO:0000269|PubMed:18936157}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q674R7-1; Sequence=Displayed; CC Name=2; CC IsoId=Q674R7-2; Sequence=VSP_030410, VSP_030413; CC Name=3; CC IsoId=Q674R7-3; Sequence=VSP_030411, VSP_030412; CC -!- TISSUE SPECIFICITY: Highly expressed in placenta (trophoblast cells) CC and pituitary gland. Not expressed in vascular endothelial. CC {ECO:0000269|PubMed:15234981}. CC -!- INDUCTION: By hypoxia, leading to inhibit NOS3 expression. CC {ECO:0000269|PubMed:17403686}. 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 ATG9B-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 -!- MISCELLANEOUS: ATG9B gene is located on the opposite DNA strand of the CC NOS3 gene at chromosome 7q36. The genes are oriented in a tail-to-tail CC configuration and the mRNAs encoding ATG9B and NOS3 are complementary CC for 662 nucleotides. ATG9B transcription may a role in NOS3 CC transcription regulation. {ECO:0000269|PubMed:15234981}. CC -!- SIMILARITY: Belongs to the ATG9 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAQ86941.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=AC010973; Type=Frameshift; Evidence={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; AY515311; AAS87212.1; -; mRNA. DR EMBL; AY316116; AAQ86941.1; ALT_INIT; mRNA. DR EMBL; AK096734; BAC04853.1; -; mRNA. DR EMBL; AC010973; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC128587; AAI28588.1; -; mRNA. DR EMBL; BK004019; DAA05200.1; -; mRNA. DR CCDS; CCDS83242.1; -. [Q674R7-1] DR RefSeq; NP_001303985.1; NM_001317056.1. [Q674R7-1] DR RefSeq; XP_011514367.1; XM_011516065.1. DR RefSeq; XP_011514368.1; XM_011516066.2. DR SMR; Q674R7; -. DR BioGRID; 130263; 6. DR IntAct; Q674R7; 5. DR TCDB; 9.A.15.2.1; the autophagy-related phagophore-formation transporter (apt) family. DR GlyGen; Q674R7; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q674R7; -. DR PhosphoSitePlus; Q674R7; -. DR BioMuta; ATG9B; -. DR DMDM; 74708555; -. DR EPD; Q674R7; -. DR jPOST; Q674R7; -. DR MassIVE; Q674R7; -. DR MaxQB; Q674R7; -. DR PeptideAtlas; Q674R7; -. DR PRIDE; Q674R7; -. DR ProteomicsDB; 65973; -. [Q674R7-1] DR ProteomicsDB; 65974; -. [Q674R7-2] DR ProteomicsDB; 65975; -. [Q674R7-3] DR Antibodypedia; 32933; 269 antibodies. DR DNASU; 285973; -. DR Ensembl; ENST00000469530; ENSP00000479879; ENSG00000181652. [Q674R7-1] DR Ensembl; ENST00000605952; ENSP00000475737; ENSG00000181652. [Q674R7-1] DR Ensembl; ENST00000639579; ENSP00000491504; ENSG00000181652. [Q674R7-1] DR GeneID; 285973; -. DR KEGG; hsa:285973; -. DR UCSC; uc064jfi.1; human. [Q674R7-1] DR CTD; 285973; -. DR DisGeNET; 285973; -. DR GeneCards; ATG9B; -. DR HGNC; HGNC:21899; ATG9B. DR HPA; ENSG00000181652; Tissue enriched (placenta). DR MIM; 612205; gene. DR neXtProt; NX_Q674R7; -. DR OpenTargets; ENSG00000181652; -. DR PharmGKB; PA134883165; -. DR VEuPathDB; HostDB:ENSG00000181652; -. DR GeneTree; ENSGT00390000014839; -. DR HOGENOM; CLU_006200_2_0_1; -. DR InParanoid; Q674R7; -. DR OMA; QQWGTQR; -. DR OrthoDB; 712239at2759; -. DR PhylomeDB; Q674R7; -. DR PathwayCommons; Q674R7; -. DR Reactome; R-HSA-1632852; Macroautophagy. DR BioGRID-ORCS; 285973; 8 hits in 164 CRISPR screens. DR GenomeRNAi; 285973; -. DR Pharos; Q674R7; Tbio. DR PRO; PR:Q674R7; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; Q674R7; protein. DR Bgee; ENSG00000181652; Expressed in lower esophagus mucosa and 142 other tissues. DR Genevisible; Q674R7; HS. DR GO; GO:0005776; C:autophagosome; IBA:GO_Central. DR GO; GO:0000421; C:autophagosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW. DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW. DR GO; GO:0000407; C:phagophore assembly site; IBA:GO_Central. DR GO; GO:0000045; P:autophagosome assembly; IDA:MGI. DR GO; GO:0000422; P:autophagy of mitochondrion; IBA:GO_Central. DR GO; GO:0044805; P:late nucleophagy; IBA:GO_Central. DR GO; GO:0034497; P:protein localization to phagophore assembly site; IBA:GO_Central. DR InterPro; IPR007241; Autophagy-rel_prot_9. DR PANTHER; PTHR13038; PTHR13038; 1. DR Pfam; PF04109; APG9; 1. PE 1: Evidence at protein level; KW Alternative splicing; Autophagy; Lipid transport; Membrane; KW Reference proteome; Transmembrane; Transmembrane helix; Transport. FT CHAIN 1..924 FT /note="Autophagy-related protein 9B" FT /id="PRO_0000314867" FT TOPO_DOM 1..207 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 208..228 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 229..276 FT /note="Lumenal" FT /evidence="ECO:0000305" FT TRANSMEM 277..297 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 298..438 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT INTRAMEM 439..459 FT /evidence="ECO:0000250|UniProtKB:Q7Z3C6" FT TOPO_DOM 460..526 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 527..547 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 548..551 FT /note="Lumenal" FT /evidence="ECO:0000305" FT TRANSMEM 552..572 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 573..624 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT INTRAMEM 625..645 FT /evidence="ECO:0000250|UniProtKB:Q7Z3C6" FT TOPO_DOM 646..924 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT REGION 1..144 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 847..924 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 151..154 FT /note="Tyrosine-based sorting signal" FT /evidence="ECO:0000250|UniProtKB:Q7Z3C6" FT COMPBIAS 26..42 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 54..95 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 102..121 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 874..916 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT VAR_SEQ 1..514 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_030410" FT VAR_SEQ 322..340 FT /note="EELSSVPWAEVQSRLLALQ -> GKGREDTGMYWRGQPGGLD (in FT isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_030411" FT VAR_SEQ 341..924 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_030412" FT VAR_SEQ 515..572 FT /note="RTAAPPAPLRTLLARQLVFFAGALFAALLVLTVYDEDVLAVEHVLTAMTALG FT VTATVA -> MPSYPQPSVLRGSAPARCWSSSWSWLPASGWSNCFAQSATSSATGTSRC FT FTGRPCTSP (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_030413" FT VARIANT 166 FT /note="P -> L (in dbSNP:rs61078191)" FT /id="VAR_061030" FT CONFLICT 12 FT /note="R -> K (in Ref. 2; BAC04853)" FT /evidence="ECO:0000305" FT CONFLICT 751 FT /note="S -> P (in Ref. 1; AAQ86941)" FT /evidence="ECO:0000305" FT CONFLICT 752 FT /note="T -> P (in Ref. 1; AAQ86941)" FT /evidence="ECO:0000305" FT CONFLICT 760 FT /note="T -> A (in Ref. 1; AAQ86941)" FT /evidence="ECO:0000305" SQ SEQUENCE 924 AA; 101019 MW; 80C242069DF3D91E CRC64; MVSRMGWGGR RRRLGRWGDL GPGSVPLLPM PLPPPPPPSC RGPGGGRISI FSLSPAPHTR SSPSSFSPPT AGPPCSVLQG TGASQSCHSA LPIPATPPTQ AQPAMTPASA SPSWGSHSTP PLAPATPTPS QQCPQDSPGL RVGPLIPEQD YERLEDCDPE GSQDSPIHGE EQQPLLHVPE GLRGSWHHIQ NLDSFFTKIY SYHQRNGFAC ILLEDVFQLG QFIFIVTFTT FLLRCVDYNV LFANQPSNHT RPGPFHSKVT LSDAILPSAQ CAERIRSSPL LVLLLVLAAG FWLVQLLRSV CNLFSYWDIQ VFYREALHIP PEELSSVPWA EVQSRLLALQ RSGGLCVQPR PLTELDIHHR ILRYTNYQVA LANKGLLPAR CPLPWGGSAA FLSRGLALNV DLLLFRGPFS LFRGGWELPH AYKRSDQRGA LAARWGRTVL LLAALNLALS PLVLAWQVLH VFYSHVELLR REPGALGARG WSRLARLQLR HFNELPHELR ARLARAYRPA AAFLRTAAPP APLRTLLARQ LVFFAGALFA ALLVLTVYDE DVLAVEHVLT AMTALGVTAT VARSFIPEEQ CQGRAPQLLL QTALAHMHYL PEEPGPGGRD RAYRQMAQLL QYRAVSLLEE LLSPLLTPLF LLFWFRPRAL EIIDFFHHFT VDVAGVGDIC SFALMDVKRH GHPQWLSAGQ TEASLSQRAE DGKTELSLMR FSLAHPLWRP PGHSSKFLGH LWGRVQQDAA AWGATSARGP STPGVLSNCT SPLPEAFLAN LFVHPLLPPR DLSPTAPCPA AATASLLASI SRIAQDPSSV SPGGTGGQKL AQLPELASAE MSLHVIYLHQ LHQQQQQQEP WGEAAASILS RPCSSPSQPP SPDEEKPSWS SDGSSPASSP RQQWGTQKAR NLFPGGFQVT TDTQKEPDRA SCTD //