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Protein

Autophagy-related protein 16-1

Gene

ATG16L1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Plays an essential role in autophagy: interacts with ATG12-ATG5 to mediate the conjugation of phosphatidylethanolamine (PE) to LC3 (MAP1LC3A, MAP1LC3B or MAP1LC3C), to produce a membrane-bound activated form of LC3 named LC3-II. Thereby, controls the elongation of the nascent autophagosomal membrane (PubMed:24553140, PubMed:23376921, PubMed:24954904, PubMed:27273576, PubMed:23392225). Regulates mitochondrial antiviral signaling (MAVS)-dependent type I interferon (IFN-I) production (PubMed:25645662). Negatively regulates NOD1- and NOD2-driven inflammatory cytokine response (PubMed:24238340). Plays a role in regulating morphology and function of Paneth cell (PubMed:18849966).8 Publications

GO - Molecular functioni

  • GTPase binding Source: UniProtKB
  • identical protein binding Source: IntAct
  • ubiquitin-like protein transferase activity Source: Reactome

GO - Biological processi

Keywordsi

Biological processAutophagy, Protein transport, Transport

Enzyme and pathway databases

ReactomeiR-HSA-1632852. Macroautophagy.
SignaLinkiQ676U5.
SIGNORiQ676U5.

Names & Taxonomyi

Protein namesi
Recommended name:
Autophagy-related protein 16-1
Alternative name(s):
APG16-like 1
Gene namesi
Name:ATG16L1
Synonyms:APG16L
ORF Names:UNQ9393/PRO34307
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000085978.21.
HGNCiHGNC:21498. ATG16L1.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Membrane

Pathology & Biotechi

Involvement in diseasei

Inflammatory bowel disease 10 (IBD10)11 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA chronic, relapsing inflammation of the gastrointestinal tract with a complex etiology. It is subdivided into Crohn disease and ulcerative colitis phenotypes. Crohn disease may affect any part of the gastrointestinal tract from the mouth to the anus, but most frequently it involves the terminal ileum and colon. Bowel inflammation is transmural and discontinuous; it may contain granulomas or be associated with intestinal or perianal fistulas. In contrast, in ulcerative colitis, the inflammation is continuous and limited to rectal and colonic mucosal layers; fistulas and granulomas are not observed. Both diseases include extraintestinal inflammation of the skin, eyes, or joints.
See also OMIM:611081
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_021834300T → A in IBD10; has no effect on the stability of the protein under normal conditions; enhances the cleavage and the degradation mediated by activated CASP3; results in reduced autophagy and defective clearance of intestinal pathogens; impairs interaction with TMEM59; slows TMEM59 intracellular trafficking; increases production of type I IFNs. 11 PublicationsCorresponds to variant dbSNP:rs2241880Ensembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi17I → W: Abolishes interaction with ATG5. 1 Publication1
Mutagenesisi21L → W: Abolishes interaction with ATG5. 1 Publication1
Mutagenesisi24R → D: Abolishes interaction with ATG5. 1 Publication1
Mutagenesisi36I → W: Reduces interaction with ATG5. 1 Publication1
Mutagenesisi139S → A: Abolishes phosphorylation. Impairs interaction with ATG12-ATG5 complex. 1 Publication1
Mutagenesisi226E → R: Impairs interaction with WIPI2. 1 Publication1
Mutagenesisi230E → R: Impairs interaction with WIPI2. 1 Publication1
Mutagenesisi299D → E: Prevents cleavage by activated CASP3. 1 Publication1
Mutagenesisi540V → A: Impairs interaction with PPP1CA; when associated with A-542. 1 Publication1
Mutagenesisi542F → A: Impairs interaction with PPP1CA; when associated with A-540. 1 Publication1

Organism-specific databases

DisGeNETi55054.
MalaCardsiATG16L1.
MIMi611081. phenotype.
OpenTargetsiENSG00000085978.
Orphaneti206. Crohn disease.
PharmGKBiPA134902949.

Polymorphism and mutation databases

BioMutaiATG16L1.
DMDMi62510482.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000508481 – 607Autophagy-related protein 16-1Add BLAST607

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei139Phosphoserine; by CK21 Publication1
Modified residuei269PhosphoserineCombined sources1
Modified residuei287PhosphoserineCombined sources1

Post-translational modificationi

Proteolytic cleavage by activated CASP3 leads to degradation and may regulate autophagy upon cellular stress and apoptotic stimuli.1 Publication
Phosphorylation at Ser-139 promotes association with the ATG12-ATG5 conjugate to form the ATG12-ATG5-ATG16L1 complex.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ676U5.
MaxQBiQ676U5.
PaxDbiQ676U5.
PeptideAtlasiQ676U5.
PRIDEiQ676U5.

PTM databases

iPTMnetiQ676U5.
PhosphoSitePlusiQ676U5.
SwissPalmiQ676U5.

Expressioni

Gene expression databases

BgeeiENSG00000085978.
CleanExiHS_ATG16L1.
ExpressionAtlasiQ676U5. baseline and differential.
GenevisibleiQ676U5. HS.

Organism-specific databases

HPAiHPA012577.
HPA063900.

Interactioni

Subunit structurei

Homodimer (PubMed:25484072). Homooligomer (By similarity). Interacts with WIPI2 (PubMed:24954904). Interacts with RB1CC1; the interaction is required for ULK1 complex-dependent autophagy (PubMed:23262492, PubMed:24954904, PubMed:23392225). Interacts with ATG5 (PubMed:23202584, PubMed:24191030, PubMed:25484072, PubMed:26812546). 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) (PubMed:26083323, PubMed:23202584, PubMed:24191030). Interacts with RAB33B (PubMed:21808068). Interacts (via WD repeats) with TMEM59; the interaction mediates unconventional autophagic activity of TMEM59 (PubMed:23376921, PubMed:27273576). Interacts with TLR2 and NOD2 (PubMed:23376921). Interacts (via WD repeats) with MEFV (PubMed:26347139). Interacts with PPP1CA; the interaction dephosphorylates ATG16L1 causing dissociation of ATG12-ATG5-ATG16L1 complex (PubMed:26083323). Interacts (via N-terminal) with CLTC (PubMed:20639872).By similarity13 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • GTPase binding Source: UniProtKB
  • identical protein binding Source: IntAct

Protein-protein interaction databases

BioGridi120375. 51 interactors.
CORUMiQ676U5.
DIPiDIP-27552N.
DIP-50290N.
IntActiQ676U5. 37 interactors.
MINTiMINT-1141152.
STRINGi9606.ENSP00000375872.

Structurei

Secondary structure

1607
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi12 – 28Combined sources17
Helixi30 – 42Combined sources13
Beta strandi313 – 319Combined sources7
Beta strandi321 – 323Combined sources3
Beta strandi325 – 330Combined sources6
Beta strandi334 – 341Combined sources8
Beta strandi346 – 351Combined sources6
Beta strandi356 – 362Combined sources7
Beta strandi369 – 374Combined sources6
Beta strandi378 – 385Combined sources8
Beta strandi390 – 394Combined sources5
Turni395 – 398Combined sources4
Beta strandi399 – 404Combined sources6
Beta strandi411 – 416Combined sources6
Beta strandi422 – 427Combined sources6
Beta strandi430 – 436Combined sources7
Turni437 – 440Combined sources4
Beta strandi441 – 447Combined sources7
Beta strandi452 – 457Combined sources6
Beta strandi459 – 466Combined sources8
Beta strandi469 – 475Combined sources7
Turni476 – 479Combined sources4
Beta strandi480 – 486Combined sources7
Beta strandi491 – 496Combined sources6
Beta strandi502 – 507Combined sources6
Turni508 – 510Combined sources3
Beta strandi511 – 516Combined sources6
Turni517 – 520Combined sources4
Beta strandi521 – 526Combined sources6
Beta strandi540 – 542Combined sources3
Beta strandi546 – 552Combined sources7
Beta strandi558 – 562Combined sources5
Turni563 – 565Combined sources3
Beta strandi568 – 572Combined sources5
Beta strandi580 – 585Combined sources6
Beta strandi592 – 596Combined sources5
Beta strandi599 – 605Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4GDKX-ray2.70C/F11-43[»]
4GDLX-ray2.88C11-43[»]
4NAWX-ray2.20C/G/K/O11-43[»]
4TQ0X-ray2.70B/D/F1-69[»]
5D7GX-ray3.00B/D/F/H1-69[»]
5NPVX-ray3.10B/D11-307[»]
5NPWX-ray3.10B/D/F/H11-307[»]
5NUVX-ray1.55A303-607[»]
ProteinModelPortaliQ676U5.
SMRiQ676U5.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati320 – 359WD 1PROSITE-ProRule annotationAdd BLAST40
Repeati364 – 403WD 2PROSITE-ProRule annotationAdd BLAST40
Repeati406 – 445WD 3PROSITE-ProRule annotationAdd BLAST40
Repeati447 – 484WD 4PROSITE-ProRule annotationAdd BLAST38
Repeati486 – 525WD 5PROSITE-ProRule annotationAdd BLAST40
Repeati532 – 573WD 6PROSITE-ProRule annotationAdd BLAST42
Repeati575 – 607WD 7PROSITE-ProRule annotationAdd BLAST33

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni13 – 43Interaction with ATG51 PublicationAdd BLAST31
Regioni207 – 230WIPI2-binding1 PublicationAdd BLAST24
Regioni230 – 242RB1CC1-binding2 PublicationsAdd BLAST13

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili78 – 230Sequence analysisAdd BLAST153

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi296 – 299Caspase cleavage4

Sequence similaritiesi

Belongs to the WD repeat ATG16 family.Curated

Keywords - Domaini

Coiled coil, Repeat, WD repeat

Phylogenomic databases

eggNOGiKOG0288. Eukaryota.
ENOG410XQYA. LUCA.
GeneTreeiENSGT00810000125363.
HOGENOMiHOG000112569.
HOVERGENiHBG050534.
InParanoidiQ676U5.
KOiK17890.
PhylomeDBiQ676U5.
TreeFamiTF315541.

Family and domain databases

Gene3Di2.130.10.10. 2 hits.
InterProiView protein in InterPro
IPR013923. Autophagy-rel_prot_16.
IPR020472. G-protein_beta_WD-40_rep.
IPR015943. WD40/YVTN_repeat-like_dom_sf.
IPR001680. WD40_repeat.
IPR019775. WD40_repeat_CS.
IPR017986. WD40_repeat_dom.
IPR036322. WD40_repeat_dom_sf.
PfamiView protein in Pfam
PF08614. ATG16. 1 hit.
PF00400. WD40. 5 hits.
PRINTSiPR00320. GPROTEINBRPT.
SMARTiView protein in SMART
SM00320. WD40. 7 hits.
SUPFAMiSSF50978. SSF50978. 1 hit.
PROSITEiView protein in PROSITE
PS00678. WD_REPEATS_1. 3 hits.
PS50082. WD_REPEATS_2. 6 hits.
PS50294. WD_REPEATS_REGION. 1 hit.

Sequences (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q676U5-1) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MSSGLRAADF PRWKRHISEQ LRRRDRLQRQ AFEEIILQYN KLLEKSDLHS
60 70 80 90 100
VLAQKLQAEK HDVPNRHEIS PGHDGTWNDN QLQEMAQLRI KHQEELTELH
110 120 130 140 150
KKRGELAQLV IDLNNQMQRK DREMQMNEAK IAECLQTISD LETECLDLRT
160 170 180 190 200
KLCDLERANQ TLKDEYDALQ ITFTALEGKL RKTTEENQEL VTRWMAEKAQ
210 220 230 240 250
EANRLNAENE KDSRRRQARL QKELAEAAKE PLPVEQDDDI EVIVDETSDH
260 270 280 290 300
TEETSPVRAI SRAATKRLSQ PAGGLLDSIT NIFGRRSVSS FPVPQDNVDT
310 320 330 340 350
HPGSGKEVRV PATALCVFDA HDGEVNAVQF SPGSRLLATG GMDRRVKLWE
360 370 380 390 400
VFGEKCEFKG SLSGSNAGIT SIEFDSAGSY LLAASNDFAS RIWTVDDYRL
410 420 430 440 450
RHTLTGHSGK VLSAKFLLDN ARIVSGSHDR TLKLWDLRSK VCIKTVFAGS
460 470 480 490 500
SCNDIVCTEQ CVMSGHFDKK IRFWDIRSES IVREMELLGK ITALDLNPER
510 520 530 540 550
TELLSCSRDD LLKVIDLRTN AIKQTFSAPG FKCGSDWTRV VFSPDGSYVA
560 570 580 590 600
AGSAEGSLYI WSVLTGKVEK VLSKQHSSSI NAVAWSPSGS HVVSVDKGCK

AVLWAQY
Length:607
Mass (Da):68,265
Last modified:April 12, 2005 - v2
Checksum:i5A5816AE2CF03CA0
GO
Isoform 2 (identifier: Q676U5-2) [UniParc]FASTAAdd to basket

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

Show »
Length:588
Mass (Da):66,296
Checksum:i168A0E53B2190149
GO
Isoform 3 (identifier: Q676U5-3) [UniParc]FASTAAdd to basket

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

Note: No experimental confirmation available. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Show »
Length:470
Mass (Da):53,220
Checksum:i7598952D2C1F2A79
GO
Isoform 4 (identifier: Q676U5-4) [UniParc]FASTAAdd to basket

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

Note: No experimental confirmation available.
Show »
Length:428
Mass (Da):47,686
Checksum:iE4F476255CDCA0A7
GO
Isoform 5 (identifier: Q676U5-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     70-213: Missing.
     266-284: Missing.

Note: No experimental confirmation available.
Show »
Length:444
Mass (Da):49,486
Checksum:i7F0FE84A72D619F9
GO

Sequence cautioni

The sequence BAB15448 differs from that shown. Reason: Erroneous translation. Wrong choice of CDS.Curated
The sequence BAB55412 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti151K → R in BAB55412 (Ref. 6) Curated1
Sequence conflicti328V → A in BAB55412 (Ref. 6) Curated1
Sequence conflicti529P → T in BAB55412 (Ref. 6) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_021834300T → A in IBD10; has no effect on the stability of the protein under normal conditions; enhances the cleavage and the degradation mediated by activated CASP3; results in reduced autophagy and defective clearance of intestinal pathogens; impairs interaction with TMEM59; slows TMEM59 intracellular trafficking; increases production of type I IFNs. 11 PublicationsCorresponds to variant dbSNP:rs2241880Ensembl.1
Natural variantiVAR_053386307E → K. Corresponds to variant dbSNP:rs1866878Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_01338970 – 213Missing in isoform 4 and isoform 5. 2 PublicationsAdd BLAST144
Alternative sequenceiVSP_013386266 – 284Missing in isoform 2 and isoform 5. 3 PublicationsAdd BLAST19
Alternative sequenceiVSP_013390334 – 368Missing in isoform 4. 1 PublicationAdd BLAST35
Alternative sequenceiVSP_013387443 – 470IKTVF…HFDKK → EEIQSLCLCICLDVSVEVCV CTSEPAFM in isoform 3. 1 PublicationAdd BLAST28
Alternative sequenceiVSP_013388471 – 607Missing in isoform 3. 1 PublicationAdd BLAST137

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY398617 mRNA. Translation: AAR32130.1.
EF079889 mRNA. Translation: ABN48554.1.
EF079890 mRNA. Translation: ABN48555.1.
AY358182 mRNA. Translation: AAQ88549.1.
AK026330 mRNA. Translation: BAB15448.1. Sequence problems.
AK027854 mRNA. Translation: BAB55412.1. Different initiation.
AK123876 mRNA. Translation: BAC85713.1.
AC013726 Genomic DNA. No translation available.
CH471063 Genomic DNA. Translation: EAW71034.1.
BC071846 mRNA. Translation: AAH71846.1.
AL834526 mRNA. Translation: CAD39182.1.
CCDSiCCDS2502.2. [Q676U5-2]
CCDS2503.2. [Q676U5-1]
CCDS54438.1. [Q676U5-5]
RefSeqiNP_001177195.1. NM_001190266.1.
NP_001177196.1. NM_001190267.1.
NP_060444.3. NM_017974.3. [Q676U5-2]
NP_110430.5. NM_030803.6. [Q676U5-1]
NP_942593.2. NM_198890.2. [Q676U5-5]
UniGeneiHs.529322.

Genome annotation databases

EnsembliENST00000347464; ENSP00000318259; ENSG00000085978. [Q676U5-5]
ENST00000373525; ENSP00000362625; ENSG00000085978. [Q676U5-4]
ENST00000392017; ENSP00000375872; ENSG00000085978. [Q676U5-1]
ENST00000392020; ENSP00000375875; ENSG00000085978. [Q676U5-2]
ENST00000625501; ENSP00000487542; ENSG00000281089. [Q676U5-1]
ENST00000626623; ENSP00000487298; ENSG00000281089. [Q676U5-5]
ENST00000630066; ENSP00000487446; ENSG00000281089. [Q676U5-2]
ENST00000630204; ENSP00000487455; ENSG00000281089. [Q676U5-4]
GeneIDi55054.
KEGGihsa:55054.
UCSCiuc002vtx.3. human. [Q676U5-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiA16L1_HUMAN
AccessioniPrimary (citable) accession number: Q676U5
Secondary accession number(s): A3EXK9
, A3EXL0, B6ZDH0, Q6IPN1, Q6UXW4, Q6ZVZ5, Q8NCY2, Q96JV5, Q9H619
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 12, 2005
Last sequence update: April 12, 2005
Last modified: November 22, 2017
This is version 146 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families