ID A16L1_HUMAN Reviewed; 607 AA. AC Q676U5; A3EXK9; Q6IPN1; Q6UXW4; Q6ZVZ5; Q8NCY2; Q96JV5; Q9H619; DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot. DT 12-APR-2005, sequence version 2. DT 07-JUL-2009, entry version 61. DE RecName: Full=Autophagy-related protein 16-1; DE AltName: Full=APG16-like 1; GN Name=ATG16L1; Synonyms=APG16L; ORFNames=UNQ9393/PRO34307; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ALA-300. RC TISSUE=Fetal brain; RX PubMed=15620219; DOI=10.1080/10425170400004104; RA Zheng H., Ji C., Li J., Jiang H., Ren M., Lu Q., Gu S., Mao Y., RA Xie Y.; RT "Cloning and analysis of human Apg16L."; RL DNA Seq. 15:303-305(2004). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND ASSOCIATION OF VARIANT RP ALA-300 WITH SUSCEPTIBILITY TO IBD10. RX PubMed=17200669; DOI=10.1038/ng1954; RA Hampe J., Franke A., Rosenstiel P., Till A., Teuber M., Huse K., RA Albrecht M., Mayr G., De La Vega F.M., Briggs J., Guenther S., RA Prescott N.J., Onnie C.M., Haesler R., Sipos B., Foelsch U.R., RA Lengauer T., Platzer M., Mathew C.G., Krawczak M., Schreiber S.; RT "A genome-wide association scan of nonsynonymous SNPs identifies a RT susceptibility variant for Crohn disease in ATG16L1."; RL Nat. Genet. 39:207-211(2007). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RX MEDLINE=22887296; PubMed=12975309; DOI=10.1101/gr.1293003; RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., RA Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., RA Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., RA Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., RA Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., RA Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., RA Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale RT effort to identify novel human secreted and transmembrane proteins: a RT bioinformatics assessment."; RL Genome Res. 13:2265-2270(2003). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), AND NUCLEOTIDE RP SEQUENCE [LARGE SCALE MRNA] OF 55-607 (ISOFORM 2). RC TISSUE=Brain, Placenta, and Small intestine; 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 114-607 (ISOFORM 2). RC TISSUE=Mammary gland; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 513-607. RC TISSUE=Testis; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Blocker H., RA Heubner D., Hoerlein A., Michel G., Wedler H., Kohrer K., RA Ottenwalder B., Poustka A., Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-287; SER-290 AND RP SER-304, AND MASS SPECTROMETRY. RC TISSUE=Epithelium; RX PubMed=17924679; DOI=10.1021/pr070152u; RA Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.; RT "Improved titanium dioxide enrichment of phosphopeptides from HeLa RT cells and high confident phosphopeptide identification by cross- RT validation of MS/MS and MS/MS/MS spectra."; RL J. Proteome Res. 6:4150-4162(2007). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-287, AND MASS RP SPECTROMETRY. RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [10] RP ASSOCIATION OF VARIANT ALA-300 WITH SUSCEPTIBILITY TO IBD10. RX PubMed=17435756; DOI=10.1038/ng2032; RA Rioux J.D., Xavier R.J., Taylor K.D., Silverberg M.S., Goyette P., RA Huett A., Green T., Kuballa P., Barmada M.M., Datta L.W., RA Shugart Y.Y., Griffiths A.M., Targan S.R., Ippoliti A.F., RA Bernard E.-J., Mei L., Nicolae D.L., Regueiro M., Schumm L.P., RA Steinhart A.H., Rotter J.I., Duerr R.H., Cho J.H., Daly M.J., RA Brant S.R.; RT "Genome-wide association study identifies new susceptibility loci for RT Crohn disease and implicates autophagy in disease pathogenesis."; RL Nat. Genet. 39:596-604(2007). CC -!- FUNCTION: Plays an essential role in autophagy (By similarity). CC -!- SUBUNIT: Homooligomer. Interacts with ATG5. Part of either the CC minor and major complexes respectively composed of 4 sets of CC ATG12-ATG5 and ATG16L1 (400 kDa) or 8 sets of ATG12-ATG5 and CC ATG16L1 (800 kDa) (By similarity). CC -!- INTERACTION: CC O94817:ATG12; NbExp=1; IntAct=EBI-535909, EBI-746742; CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity). Preautophagosomal CC structure membrane; Peripheral membrane protein (By similarity). CC Note=Localized to preautophagosomal structure (PAS) where it is CC involved in the membrane targeting of ATG5 (By similarity). CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; Synonyms=APG16L beta; CC IsoId=Q676U5-1; Sequence=Displayed; CC Name=2; CC IsoId=Q676U5-2; Sequence=VSP_013386; CC Note=May be produced at very low levels due to a premature stop CC codon in the mRNA, leading to nonsense-mediated mRNA decay; CC Name=3; CC IsoId=Q676U5-3; Sequence=VSP_013387, VSP_013388; CC Note=No experimental confirmation available; CC Name=4; CC IsoId=Q676U5-4; Sequence=VSP_013389, VSP_013390; CC Note=No experimental confirmation available; CC -!- DISEASE: Genetic variations in ATG16L1 are associated with CC susceptibility to inflammatory bowel disease type 10 (IBD10) CC [MIM:611081]. IBD is characterized by a chronic relapsing CC intestinal inflammation. IBD is subdivided into Crohn disease (CD) CC and ulcerative colitis phenotypes. IBD10 individuals show the CC phenotype characteristic to CD. It may involve any part of the CC gastrointestinal tract, but most frequently the terminal ileum and CC colon. CD is commonly classified as autoimmune disease. CC -!- SIMILARITY: Belongs to the WD repeat ATG16 family. CC -!- SIMILARITY: Contains 7 WD repeats. CC -!- SEQUENCE CAUTION: CC Sequence=BAB15448.1; Type=Erroneous translation; Note=Wrong choice of CDS; 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; AY398617; AAR32130.1; -; mRNA. DR EMBL; EF079889; ABN48554.1; -; mRNA. DR EMBL; AY358182; AAQ88549.1; -; mRNA. DR EMBL; AK026330; BAB15448.1; ALT_SEQ; mRNA. DR EMBL; AK027854; BAB55412.1; ALT_INIT; mRNA. DR EMBL; AK123876; BAC85713.1; -; mRNA. DR EMBL; CH471063; EAW71034.1; -; Genomic_DNA. DR EMBL; BC071846; AAH71846.1; -; mRNA. DR EMBL; AL834526; CAD39182.1; -; mRNA. DR IPI; IPI00432751; -. DR IPI; IPI00446614; -. DR IPI; IPI00470446; -. DR IPI; IPI00555905; -. DR RefSeq; NP_110430.5; -. DR UniGene; Hs.529322; -. DR HSSP; P16649; 1ERJ. DR IntAct; Q676U5; 2. DR PhosphoSite; Q676U5; -. DR PRIDE; Q676U5; -. DR Ensembl; ENSG00000085978; Homo sapiens. DR GeneID; 55054; -. DR UCSC; uc002vty.1; human. DR UCSC; uc002vtz.1; human. DR UCSC; uc002vua.1; human. DR GeneCards; GC02P233825; -. DR H-InvDB; HIX0002933; -. DR H-InvDB; HIX0009913; -. DR HGNC; HGNC:21498; ATG16L1. DR HPA; HPA012577; -. DR MIM; 610767; gene. DR MIM; 611081; phenotype. DR PharmGKB; PA134902949; -. DR HOVERGEN; Q676U5; -. DR NextBio; 58531; -. DR ArrayExpress; Q676U5; -. DR Bgee; Q676U5; -. DR CleanEx; HS_ATG16L1; -. DR GermOnline; ENSG00000085978; Homo sapiens. DR GO; GO:0005776; C:autophagic vacuole; ISS:UniProtKB. DR GO; GO:0034045; C:pre-autophagosomal structure membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005515; F:protein binding; IPI:IntAct. DR GO; GO:0000045; P:autophagic vacuole formation; NAS:UniProtKB. DR GO; GO:0051260; P:protein homooligomerization; NAS:UniProtKB. DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW. DR InterPro; IPR013923; Autophagy-rel_prot_16. DR InterPro; IPR015943; WD40/YVTN_repeat-like. DR InterPro; IPR001680; WD40_repeat. DR InterPro; IPR019782; WD40_repeat_2. DR InterPro; IPR019775; WD40_repeat_CS. DR InterPro; IPR017986; WD40_repeat_region. DR InterPro; IPR019781; WD40_repeat_sg. DR Gene3D; G3DSA:2.130.10.10; WD40/YVTN_repeat-like; 1. DR Pfam; PF08614; ATG16; 1. DR Pfam; PF00400; WD40; 6. DR ProDom; PD000018; WD40; 2. DR SMART; SM00320; WD40; 7. DR PROSITE; PS00678; WD_REPEATS_1; 3. DR PROSITE; PS50082; WD_REPEATS_2; 6. DR PROSITE; PS50294; WD_REPEATS_REGION; 1. PE 1: Evidence at protein level; KW Alternative splicing; Autophagy; Coiled coil; Complete proteome; KW Cytoplasm; Membrane; Phosphoprotein; Polymorphism; Protein transport; KW Repeat; Transport; WD repeat. FT CHAIN 1 607 Autophagy-related protein 16-1. FT /FTId=PRO_0000050848. FT REPEAT 320 359 WD 1. FT REPEAT 364 403 WD 2. FT REPEAT 406 445 WD 3. FT REPEAT 447 484 WD 4. FT REPEAT 486 525 WD 5. FT REPEAT 532 573 WD 6. FT REPEAT 575 607 WD 7. FT COILED 78 230 Potential. FT MOD_RES 287 287 Phosphoserine. FT MOD_RES 289 289 Phosphoserine (By similarity). FT MOD_RES 290 290 Phosphoserine. FT MOD_RES 304 304 Phosphoserine. FT VAR_SEQ 70 213 Missing (in isoform 4). FT /FTId=VSP_013389. FT VAR_SEQ 266 284 Missing (in isoform 2). FT /FTId=VSP_013386. FT VAR_SEQ 334 368 Missing (in isoform 4). FT /FTId=VSP_013390. FT VAR_SEQ 443 470 IKTVFAGSSCNDIVCTEQCVMSGHFDKK -> EEIQSLCLC FT ICLDVSVEVCVCTSEPAFM (in isoform 3). FT /FTId=VSP_013387. FT VAR_SEQ 471 607 Missing (in isoform 3). FT /FTId=VSP_013388. FT VARIANT 300 300 T -> A (associated with susceptibility to FT IBD10; dbSNP:rs2241880). FT /FTId=VAR_021834. FT VARIANT 307 307 E -> K (in dbSNP:rs1866878). FT /FTId=VAR_053386. FT CONFLICT 151 151 K -> R (in Ref. 5; BAB55412). FT CONFLICT 328 328 V -> A (in Ref. 5; BAB55412). FT CONFLICT 529 529 P -> T (in Ref. 5; BAB55412). SQ SEQUENCE 607 AA; 68265 MW; 5A5816AE2CF03CA0 CRC64; MSSGLRAADF PRWKRHISEQ LRRRDRLQRQ AFEEIILQYN KLLEKSDLHS VLAQKLQAEK HDVPNRHEIS PGHDGTWNDN QLQEMAQLRI KHQEELTELH KKRGELAQLV IDLNNQMQRK DREMQMNEAK IAECLQTISD LETECLDLRT KLCDLERANQ TLKDEYDALQ ITFTALEGKL RKTTEENQEL VTRWMAEKAQ EANRLNAENE KDSRRRQARL QKELAEAAKE PLPVEQDDDI EVIVDETSDH TEETSPVRAI SRAATKRLSQ PAGGLLDSIT NIFGRRSVSS FPVPQDNVDT HPGSGKEVRV PATALCVFDA HDGEVNAVQF SPGSRLLATG GMDRRVKLWE VFGEKCEFKG SLSGSNAGIT SIEFDSAGSY LLAASNDFAS RIWTVDDYRL RHTLTGHSGK VLSAKFLLDN ARIVSGSHDR TLKLWDLRSK VCIKTVFAGS SCNDIVCTEQ CVMSGHFDKK IRFWDIRSES IVREMELLGK ITALDLNPER TELLSCSRDD LLKVIDLRTN AIKQTFSAPG FKCGSDWTRV VFSPDGSYVA AGSAEGSLYI WSVLTGKVEK VLSKQHSSSI NAVAWSPSGS HVVSVDKGCK AVLWAQY //