Reviewed, UniProtKB/Swiss-Prot Q676U5 (A16L1_HUMAN)

Names and origin

Protein names

Recommended name:
    Autophagy-related protein 16-1
Alternative name(s):
    APG16-like 1

Gene names

Name:	ATG16L1
Synonyms:	APG16L
ORF Names:	UNQ9393/PRO34307

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	607 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Plays an essential role in autophagy By similarity.
Subunit structure	Homooligomer. Interacts with ATG5. Part of either the minor and major complexes respectively composed of 4 sets of ATG12-ATG5 and ATG16L1 (400 kDa) or 8 sets of ATG12-ATG5 and ATG16L1 (800 kDa) By similarity.
Subcellular location	Cytoplasm By similarity. Preautophagosomal structure membrane; Peripheral membrane protein By similarity. Note: Localized to preautophagosomal structure (PAS) where it is involved in the membrane targeting of ATG5 By similarity.
Involvement in disease	Genetic variations in ATG16L1 are associated with susceptibility to inflammatory bowel disease type 10 (IBD10) [MIM:611081]. IBD is characterized by a chronic relapsing intestinal inflammation. IBD is subdivided into Crohn disease (CD) and ulcerative colitis phenotypes. IBD10 individuals show the phenotype characteristic to CD. It may involve any part of the gastrointestinal tract, but most frequently the terminal ileum and colon. CD is commonly classified as autoimmune disease. Ref.2 Ref.10
Sequence similarities	Belongs to the WD repeat ATG16 family. Contains 7 WD repeats.
Sequence caution	The sequence BAB15448.1 differs from that shown. Reason: Erroneous translation. Wrong choice of CDS.

Ontologies

Keywords
Biological process	Autophagy Protein transport Transport
Cellular component	Cytoplasm Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Coiled coil Repeat WD repeat
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	autophagic vacuole formation Ref.1 Non-traceable author statement. Source: UniProtKB protein homooligomerization Ref.1 Non-traceable author statement. Source: UniProtKB protein transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	autophagic vacuole Ref.1 Inferred from sequence or structural similarity. Source: UniProtKB pre-autophagosomal structure membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ATG12	O94817	1	EBI-535909,EBI-746742

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q676U5-1)

Also known as: APG16L beta;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q676U5-2)

The sequence of this isoform differs from the canonical sequence as follows:
     266-284: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoform 3 (identifier: Q676U5-3)

The sequence of this isoform differs from the canonical sequence as follows:
     443-470: IKTVFAGSSCNDIVCTEQCVMSGHFDKK → EEIQSLCLCICLDVSVEVCVCTSEPAFM
     471-607: Missing.

Note: No experimental confirmation available.

Isoform 4 (identifier: Q676U5-4)

The sequence of this isoform differs from the canonical sequence as follows:
     70-213: Missing.
     334-368: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 607	607	Autophagy-related protein 16-1		PRO_0000050848
Regions
	Repeat	320 – 359	40	WD 1
	Repeat	364 – 403	40	WD 2
	Repeat	406 – 445	40	WD 3
	Repeat	447 – 484	38	WD 4
	Repeat	486 – 525	40	WD 5
	Repeat	532 – 573	42	WD 6
	Repeat	575 – 607	33	WD 7
	Coiled coil	78 – 230	153	Potential
Amino acid modifications
	Modified residue	287	1	Phosphoserine Ref.8 Ref.9
	Modified residue	289	1	Phosphoserine By similarity
	Modified residue	290	1	Phosphoserine Ref.8
	Modified residue	304	1	Phosphoserine Ref.8
Natural variations
	Alternative sequence	70 – 213	144	Missing in isoform 4.		VSP_013389
	Alternative sequence	266 – 284	19	Missing in isoform 2.		VSP_013386
	Alternative sequence	334 – 368	35	Missing in isoform 4.		VSP_013390
	Alternative sequence	443 – 470	28	IKTVF…HFDKK → EEIQSLCLCICLDVSVEVCV CTSEPAFM in isoform 3.		VSP_013387
	Alternative sequence	471 – 607	137	Missing in isoform 3.		VSP_013388
	Natural variant	300	1	T → A Associated with susceptibility to IBD10. dbSNP rs2241880. Ref.2 Ref.10 Ref.1		VAR_021834
	Natural variant	307	1	E → K: dbSNP rs1866878.		VAR_053386
Experimental info
	Sequence conflict	151	1	K → R in BAB55412. Ref.5
	Sequence conflict	328	1	V → A in BAB55412. Ref.5
	Sequence conflict	529	1	P → T in BAB55412. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (APG16L beta) [UniParc]. Last modified April 12, 2005. Version 2. Checksum: 5A5816AE2CF03CA0	FASTA	607	68,265
	10 20 30 40 50 60 MSSGLRAADF PRWKRHISEQ LRRRDRLQRQ AFEEIILQYN KLLEKSDLHS VLAQKLQAEK 70 80 90 100 110 120 HDVPNRHEIS PGHDGTWNDN QLQEMAQLRI KHQEELTELH KKRGELAQLV IDLNNQMQRK 130 140 150 160 170 180 DREMQMNEAK IAECLQTISD LETECLDLRT KLCDLERANQ TLKDEYDALQ ITFTALEGKL 190 200 210 220 230 240 RKTTEENQEL VTRWMAEKAQ EANRLNAENE KDSRRRQARL QKELAEAAKE PLPVEQDDDI 250 260 270 280 290 300 EVIVDETSDH TEETSPVRAI SRAATKRLSQ PAGGLLDSIT NIFGRRSVSS FPVPQDNVDT 310 320 330 340 350 360 HPGSGKEVRV PATALCVFDA HDGEVNAVQF SPGSRLLATG GMDRRVKLWE VFGEKCEFKG 370 380 390 400 410 420 SLSGSNAGIT SIEFDSAGSY LLAASNDFAS RIWTVDDYRL RHTLTGHSGK VLSAKFLLDN 430 440 450 460 470 480 ARIVSGSHDR TLKLWDLRSK VCIKTVFAGS SCNDIVCTEQ CVMSGHFDKK IRFWDIRSES 490 500 510 520 530 540 IVREMELLGK ITALDLNPER TELLSCSRDD LLKVIDLRTN AIKQTFSAPG FKCGSDWTRV 550 560 570 580 590 600 VFSPDGSYVA AGSAEGSLYI WSVLTGKVEK VLSKQHSSSI NAVAWSPSGS HVVSVDKGCK AVLWAQY
	Isoform 2. Checksum: 168A0E53B2190149	FASTA	588	66,296
	10 20 30 40 50 60 MSSGLRAADF PRWKRHISEQ LRRRDRLQRQ AFEEIILQYN KLLEKSDLHS VLAQKLQAEK 70 80 90 100 110 120 HDVPNRHEIS PGHDGTWNDN QLQEMAQLRI KHQEELTELH KKRGELAQLV IDLNNQMQRK 130 140 150 160 170 180 DREMQMNEAK IAECLQTISD LETECLDLRT KLCDLERANQ TLKDEYDALQ ITFTALEGKL 190 200 210 220 230 240 RKTTEENQEL VTRWMAEKAQ EANRLNAENE KDSRRRQARL QKELAEAAKE PLPVEQDDDI 250 260 270 280 290 300 EVIVDETSDH TEETSPVRAI SRAATRRSVS SFPVPQDNVD THPGSGKEVR VPATALCVFD 310 320 330 340 350 360 AHDGEVNAVQ FSPGSRLLAT GGMDRRVKLW EVFGEKCEFK GSLSGSNAGI TSIEFDSAGS 370 380 390 400 410 420 YLLAASNDFA SRIWTVDDYR LRHTLTGHSG KVLSAKFLLD NARIVSGSHD RTLKLWDLRS 430 440 450 460 470 480 KVCIKTVFAG SSCNDIVCTE QCVMSGHFDK KIRFWDIRSE SIVREMELLG KITALDLNPE 490 500 510 520 530 540 RTELLSCSRD DLLKVIDLRT NAIKQTFSAP GFKCGSDWTR VVFSPDGSYV AAGSAEGSLY 550 560 570 580 IWSVLTGKVE KVLSKQHSSS INAVAWSPSG SHVVSVDKGC KAVLWAQY
	Isoform 3. Checksum: 7598952D2C1F2A79	FASTA	470	53,220
	10 20 30 40 50 60 MSSGLRAADF PRWKRHISEQ LRRRDRLQRQ AFEEIILQYN KLLEKSDLHS VLAQKLQAEK 70 80 90 100 110 120 HDVPNRHEIS PGHDGTWNDN QLQEMAQLRI KHQEELTELH KKRGELAQLV IDLNNQMQRK 130 140 150 160 170 180 DREMQMNEAK IAECLQTISD LETECLDLRT KLCDLERANQ TLKDEYDALQ ITFTALEGKL 190 200 210 220 230 240 RKTTEENQEL VTRWMAEKAQ EANRLNAENE KDSRRRQARL QKELAEAAKE PLPVEQDDDI 250 260 270 280 290 300 EVIVDETSDH TEETSPVRAI SRAATKRLSQ PAGGLLDSIT NIFGRRSVSS FPVPQDNVDT 310 320 330 340 350 360 HPGSGKEVRV PATALCVFDA HDGEVNAVQF SPGSRLLATG GMDRRVKLWE VFGEKCEFKG 370 380 390 400 410 420 SLSGSNAGIT SIEFDSAGSY LLAASNDFAS RIWTVDDYRL RHTLTGHSGK VLSAKFLLDN 430 440 450 460 470 ARIVSGSHDR TLKLWDLRSK VCEEIQSLCL CICLDVSVEV CVCTSEPAFM
	Isoform 4. Checksum: E4F476255CDCA0A7	FASTA	428	47,686
	10 20 30 40 50 60 MSSGLRAADF PRWKRHISEQ LRRRDRLQRQ AFEEIILQYN KLLEKSDLHS VLAQKLQAEK 70 80 90 100 110 120 HDVPNRHEIR RRQARLQKEL AEAAKEPLPV EQDDDIEVIV DETSDHTEET SPVRAISRAA 130 140 150 160 170 180 TKRLSQPAGG LLDSITNIFG RRSVSSFPVP QDNVDTHPGS GKEVRVPATA LCVFDAHDGE 190 200 210 220 230 240 VNAVQFSPGI TSIEFDSAGS YLLAASNDFA SRIWTVDDYR LRHTLTGHSG KVLSAKFLLD 250 260 270 280 290 300 NARIVSGSHD RTLKLWDLRS KVCIKTVFAG SSCNDIVCTE QCVMSGHFDK KIRFWDIRSE 310 320 330 340 350 360 SIVREMELLG KITALDLNPE RTELLSCSRD DLLKVIDLRT NAIKQTFSAP GFKCGSDWTR 370 380 390 400 410 420 VVFSPDGSYV AAGSAEGSLY IWSVLTGKVE KVLSKQHSSS INAVAWSPSG SHVVSVDKGC KAVLWAQY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and analysis of human Apg16L." Zheng H., Ji C., Li J., Jiang H., Ren M., Lu Q., Gu S., Mao Y., Xie Y. DNA Seq. 15:303-305(2004) [PubMed: 15620219] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ALA-300. Tissue: Fetal brain.
[2]	"A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1." Hampe J., Franke A., Rosenstiel P., Till A., Teuber M., Huse K., Albrecht M., Mayr G., De La Vega F.M., Briggs J., Guenther S., Prescott N.J., Onnie C.M., Haesler R., Sipos B., Foelsch U.R., Lengauer T., Platzer M. , Mathew C.G., Krawczak M., Schreiber S. Nat. Genet. 39:207-211(2007) [PubMed: 17200669] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ASSOCIATION OF VARIANT ALA-300 WITH SUSCEPTIBILITY TO IBD10.
[3]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed: 12975309] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
[4]	Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 55-607 (ISOFORM 2). Tissue: Brain, Placenta and Small intestine.
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 114-607 (ISOFORM 2). Tissue: Mammary gland.
[7]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Blocker H., Heubner D., Hoerlein A., Michel G., Wedler H., Kohrer K., Ottenwalder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 513-607. Tissue: Testis.
[8]	"Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra." Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D. J. Proteome Res. 6:4150-4162(2007) [PubMed: 17924679] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-287; SER-290 AND SER-304, MASS SPECTROMETRY. Tissue: Epithelium.
[9]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-287, MASS SPECTROMETRY.
[10]	"Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis." Rioux J.D., Xavier R.J., Taylor K.D., Silverberg M.S., Goyette P., Huett A., Green T., Kuballa P., Barmada M.M., Datta L.W., Shugart Y.Y., Griffiths A.M., Targan S.R., Ippoliti A.F., Bernard E.-J., Mei L., Nicolae D.L., Regueiro M. , Schumm L.P., Steinhart A.H., Rotter J.I., Duerr R.H., Cho J.H., Daly M.J., Brant S.R. Nat. Genet. 39:596-604(2007) [PubMed: 17435756] [Abstract] Cited for: ASSOCIATION OF VARIANT ALA-300 WITH SUSCEPTIBILITY TO IBD10.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AY398617 mRNA. Translation: AAR32130.1. EF079889 mRNA. Translation: ABN48554.1. AY358182 mRNA. Translation: AAQ88549.1. AK026330 mRNA. Translation: BAB15448.1. Sequence problems. AK027854 mRNA. Translation: BAB55412.1. Different initiation. AK123876 mRNA. Translation: BAC85713.1. CH471063 Genomic DNA. Translation: EAW71034.1. BC071846 mRNA. Translation: AAH71846.1. AL834526 mRNA. Translation: CAD39182.1.
IPI	IPI00432751. IPI00446614. IPI00470446. IPI00555905.
RefSeq	NP_110430.5.
UniGene	Hs.529322
3D structure databases
HSSP	HSSP built from PDB template 1ERJ based on UniProtKB P16649.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q676U5. 2 interactions.
PTM databases
PhosphoSite	Q676U5.
Proteomic databases
PRIDE	Q676U5.
Genome annotation databases
Ensembl	ENSG00000085978. Homo sapiens. [Contig view]
GeneID	55054.
Organism-specific databases
GeneCards	GC02P233825.
H-InvDB	HIX0002933. HIX0009913.
HGNC	HGNC:21498. ATG16L1.
HPA	HPA012577.
MIM	610767. gene. 611081. phenotype.
PharmGKB	PA134902949.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q676U5.
Gene expression databases
ArrayExpress	Q676U5.
Bgee	Q676U5.
CleanEx	HS_ATG16L1.
GermOnline	ENSG00000085978. Homo sapiens.
Family and domain databases
InterPro	IPR013923. Autophagy-rel_prot_16. IPR015943. WD40/YVTN_repeat-like. IPR001680. WD40_repeat. IPR019782. WD40_repeat_2. IPR019775. WD40_repeat_CS. IPR017986. WD40_repeat_region. IPR019781. WD40_repeat_sg. [Graphical view]
Gene3D	G3DSA:2.130.10.10. WD40/YVTN_repeat-like. 1 hit.
Pfam	PF08614. ATG16. 1 hit. PF00400. WD40. 6 hits. [Graphical view]
ProDom	PD000018. WD40. 2 hits. [Graphical view] [Entries sharing at least one domain]
SMART	SM00320. WD40. 7 hits. [Graphical view]
PROSITE	PS00678. WD_REPEATS_1. 3 hits. PS50082. WD_REPEATS_2. 6 hits. PS50294. WD_REPEATS_REGION. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	58531.
SOURCE	Search...

Entry information

Entry name

A16L1_HUMAN

Accession

Primary (citable) accession number: Q676U5
Secondary accession number(s): A3EXK9 , Q6IPN1, Q6UXW4, Q6ZVZ5, Q8NCY2, Q96JV5, Q9H619

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 12, 2005
Last sequence update:	April 12, 2005
Last modified:	June 16, 2009
This is version 60 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)