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Protein

Interferon-inducible protein AIM2

Gene

AIM2

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

Functioni

Involved in innate immune response by recognizing cytosolic double-stranded DNA and inducing caspase-1-activating inflammasome formation in macrophages. Upon binding to DNA is thought to undergo oligomerization and to associate with PYCARD initiating the recruitment of caspase-1 precusrsor and processing of interleukin-1 beta and interleukin-18. Detects cytosolic dsDNA of viral and bacterial origin in a non-sequence-specific manner. Can also trigger PYCARD-dependent, caspase-1-independent cell death that involves caspase-8 (By similarity). Tumor suppressor which may act by repressing NF-kappa-B transcriptional activity.By similarity6 Publications

Miscellaneous

Defects in AIM2 may be a cause of microsatellite unstable colon cancers.

Activity regulationi

In absence of dsDNA pyrin and HIN-20 domain can interact inducing a closed conformation; an autoinhibitory mechanism is proposed in which binding to dsDNA liberates the pyrin domain for homotypic downstream signaling interactions with PYCARD.1 Publication

GO - Molecular functioni

  • double-stranded DNA binding Source: UniProtKB
  • identical protein binding Source: IntAct

GO - Biological processi

Keywordsi

Molecular functionDNA-binding
Biological processApoptosis, Immunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

ReactomeiR-HSA-844615 The AIM2 inflammasome

Names & Taxonomyi

Protein namesi
Recommended name:
Interferon-inducible protein AIM2
Alternative name(s):
Absent in melanoma 2
Gene namesi
Name:AIM2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000163568.13
HGNCiHGNC:357 AIM2
MIMi604578 gene
neXtProtiNX_O14862

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, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi14L → A: Fails to activate interleukin-1 beta production. 1 Publication1
Mutagenesisi160K → A: Impairs DNA binding; when associated with A-160; A-K162; A-163; A-198; A-204. Impairs DNA binding; when associated with A-160; A-162; A-163; A-198; A-204; A-244; A-251; A-309; A-311; A-355 and A-337. 1 Publication1
Mutagenesisi162K → A: Impairs DNA binding; when associated with A-160; A-162; A-163; A-198; A-204. Impairs DNA binding; when associated with A-160; A-162; A-163; A-198; A-204; A-244; A-251; A-309; A-311; A-355 and A-337. 1 Publication1
Mutagenesisi163K → A: Impairs DNA binding; when associated with A-160; A-162; A-163; A-198; A-204. Impairs DNA binding; when associated with A-160; A-162; A-163; A-198; A-204; A-244; A-251; A-309; A-311; A-355 and A-337. 1 Publication1
Mutagenesisi165F → A: Impairs DNA binding. 1 Publication1
Mutagenesisi198K → A: Impairs DNA binding; when associated with A-160; A-162; A-163; A-198; A-204. Impairs DNA binding; when associated with A-160; A-162; A-163; A-198; A-204; A-244; A-251; A-309; A-311; A-355 and A-337. 1 Publication1
Mutagenesisi204K → A: Impairs DNA binding; when associated with A-160; A-162; A-163; A-198; A-204. Impairs DNA binding; when associated with A-160; A-162; A-163; A-198; A-204; A-244; A-251; A-309; A-311; A-355 and A-337. 1 Publication1
Mutagenesisi244R → A: Impairs DNA binding; when associated with A-160; A-162; A-163; A-198; A-204. Impairs DNA binding; when associated with A-160; A-162; A-163; A-198; A-204; A-244; A-251; A-309; A-311; A-355 and A-337. 1 Publication1
Mutagenesisi251K → A: Impairs DNA binding; when associated with A-160; A-162; A-163; A-198; A-204. Impairs DNA binding; when associated with A-160; A-162; A-163; A-198; A-204; A-244; A-251; A-309; A-311; A-355 and A-337. 1 Publication1
Mutagenesisi309K → A: Impairs DNA binding; when associated with A-160; A-162; A-163; A-198; A-204. Impairs DNA binding; when associated with A-160; A-162; A-163; A-198; A-204; A-244; A-251; A-309; A-311; A-355 and A-337. 1 Publication1
Mutagenesisi311R → A: Impairs DNA binding; when associated with A-160; A-162; A-163; A-198; A-204. Impairs DNA binding; when associated with A-160; A-162; A-163; A-198; A-204; A-244; A-251; A-309; A-311; A-355 and A-337. 1 Publication1
Mutagenesisi335K → A: Impairs DNA binding; when associated with A-160; A-162; A-163; A-198; A-204. Impairs DNA binding; when associated with A-160; A-162; A-163; A-198; A-204; A-244; A-251; A-309; A-311; A-355 and A-337. 1 Publication1
Mutagenesisi337I → A: Impairs DNA binding; when associated with A-160; A-162; A-163; A-198; A-204. Impairs DNA binding; when associated with A-160; A-162; A-163; A-198; A-204; A-244; A-251; A-309; A-311; A-355 and A-337. 1 Publication1

Keywords - Diseasei

Tumor suppressor

Organism-specific databases

DisGeNETi9447
OpenTargetsiENSG00000163568
PharmGKBiPA24651

Polymorphism and mutation databases

BioMutaiAIM2

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001537261 – 343Interferon-inducible protein AIM2Add BLAST343

Proteomic databases

MaxQBiO14862
PaxDbiO14862
PeptideAtlasiO14862
PRIDEiO14862
ProteomicsDBi48275

PTM databases

iPTMnetiO14862
PhosphoSitePlusiO14862

Expressioni

Tissue specificityi

Expressed in spleen, small intestine, peripheral blood leukocytes, and testis.1 Publication

Inductioni

By IFNG/IFN-gamma and IFNB1/IFN-beta.3 Publications

Gene expression databases

BgeeiENSG00000163568 Expressed in 134 organ(s), highest expression level in small intestine Peyer's patch
CleanExiHS_AIM2
ExpressionAtlasiO14862 baseline and differential
GenevisibleiO14862 HS

Organism-specific databases

HPAiHPA031365
HPA040309

Interactioni

Subunit structurei

Self-associates; forms homooligomers in response to cytosolic dsDNA and the dsDNA seems to serve as oligomerization platform. Component of the AIM2 inflammasome. Interacts with PYCARD, IFI16, EIF2AK2/PKR and MAPRE1. Interacts with PYDC5; disrupts assembly of the ALR inflammasome complex (PubMed:24531343).9 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114837, 2 interactors
DIPiDIP-59741N
IntActiO14862, 109 interactors
STRINGi9606.ENSP00000357112

Structurei

Secondary structure

1343
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO14862
SMRiO14862
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 87PyrinPROSITE-ProRule annotationAdd BLAST87
Domaini138 – 337HIN-200PROSITE-ProRule annotationAdd BLAST200

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi206 – 209Poly-Ile4

Domaini

The pyrin domain mediates homotypic interaction with PYCARD (PubMed:19158676, PubMed:19158675).2 Publications
The HIN-20 domain mediates dsDNA binding via electrostatic interactions.1 Publication

Sequence similaritiesi

Belongs to the HIN-200 family.Curated

Phylogenomic databases

eggNOGiENOG410J5NP Eukaryota
ENOG410Y78B LUCA
GeneTreeiENSGT00390000013296
HOGENOMiHOG000033871
HOVERGENiHBG006122
InParanoidiO14862
KOiK12966
OMAiQEMFHAT
PhylomeDBiO14862
TreeFamiTF337385

Family and domain databases

InterProiView protein in InterPro
IPR004020 DAPIN
IPR011029 DEATH-like_dom_sf
IPR004021 HIN200/IF120x
PfamiView protein in Pfam
PF02760 HIN, 1 hit
PF02758 PYRIN, 1 hit
SMARTiView protein in SMART
SM01289 PYRIN, 1 hit
SUPFAMiSSF47986 SSF47986, 1 hit
PROSITEiView protein in PROSITE
PS50824 DAPIN, 1 hit
PS50834 HIN_200, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

O14862-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MESKYKEILL LTGLDNITDE ELDRFKFFLS DEFNIATGKL HTANRIQVAT
60 70 80 90 100
LMIQNAGAVS AVMKTIRIFQ KLNYMLLAKR LQEEKEKVDK QYKSVTKPKP
110 120 130 140 150
LSQAEMSPAA SAAIRNDVAK QRAAPKVSPH VKPEQKQMVA QQESIREGFQ
160 170 180 190 200
KRCLPVMVLK AKKPFTFETQ EGKQEMFHAT VATEKEFFFV KVFNTLLKDK
210 220 230 240 250
FIPKRIIIIA RYYRHSGFLE VNSASRVLDA ESDQKVNVPL NIIRKAGETP
260 270 280 290 300
KINTLQTQPL GTIVNGLFVV QKVTEKKKNI LFDLSDNTGK MEVLGVRNED
310 320 330 340
TMKCKEGDKV RLTFFTLSKN GEKLQLTSGV HSTIKVIKAK KKT
Length:343
Mass (Da):38,954
Last modified:January 1, 1998 - v1
Checksum:i92EC418AB28CE1E6
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q5T3W0Q5T3W0_HUMAN
Interferon-inducible protein AIM2
AIM2
167Annotation score:

Sequence cautioni

The sequence AAH10940 differs from that shown. Reason: Frameshift at position 340.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti253N → D in BAF84731 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02202232E → K1 PublicationCorresponds to variant dbSNP:rs2276405Ensembl.1
Natural variantiVAR_043379304C → Y1 PublicationCorresponds to variant dbSNP:rs778047649Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF024714 mRNA Translation: AAB81613.1
AK292042 mRNA Translation: BAF84731.1
AL359753 Genomic DNA No translation available.
BC010940 mRNA Translation: AAH10940.1 Frameshift.
CCDSiCCDS1181.1
RefSeqiNP_004824.1, NM_004833.2
XP_016858337.1, XM_017002848.1
UniGeneiHs.733411

Genome annotation databases

EnsembliENST00000368130; ENSP00000357112; ENSG00000163568
GeneIDi9447
KEGGihsa:9447
UCSCiuc001ftj.2 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF024714 mRNA Translation: AAB81613.1
AK292042 mRNA Translation: BAF84731.1
AL359753 Genomic DNA No translation available.
BC010940 mRNA Translation: AAH10940.1 Frameshift.
CCDSiCCDS1181.1
RefSeqiNP_004824.1, NM_004833.2
XP_016858337.1, XM_017002848.1
UniGeneiHs.733411

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3RN2X-ray2.55A/B144-343[»]
3RN5X-ray2.50A/B/C/D144-343[»]
3VD8X-ray2.07A1-107[»]
4O7QX-ray1.82A1-93[»]
6MB2electron microscopy5.00A/B/C/D/E/F/G/H/I/J/K/L/M/N/O1-93[»]
ProteinModelPortaliO14862
SMRiO14862
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114837, 2 interactors
DIPiDIP-59741N
IntActiO14862, 109 interactors
STRINGi9606.ENSP00000357112

PTM databases

iPTMnetiO14862
PhosphoSitePlusiO14862

Polymorphism and mutation databases

BioMutaiAIM2

Proteomic databases

MaxQBiO14862
PaxDbiO14862
PeptideAtlasiO14862
PRIDEiO14862
ProteomicsDBi48275

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000368130; ENSP00000357112; ENSG00000163568
GeneIDi9447
KEGGihsa:9447
UCSCiuc001ftj.2 human

Organism-specific databases

CTDi9447
DisGeNETi9447
EuPathDBiHostDB:ENSG00000163568.13
GeneCardsiAIM2
HGNCiHGNC:357 AIM2
HPAiHPA031365
HPA040309
MIMi604578 gene
neXtProtiNX_O14862
OpenTargetsiENSG00000163568
PharmGKBiPA24651
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410J5NP Eukaryota
ENOG410Y78B LUCA
GeneTreeiENSGT00390000013296
HOGENOMiHOG000033871
HOVERGENiHBG006122
InParanoidiO14862
KOiK12966
OMAiQEMFHAT
PhylomeDBiO14862
TreeFamiTF337385

Enzyme and pathway databases

ReactomeiR-HSA-844615 The AIM2 inflammasome

Miscellaneous databases

GeneWikiiAIM2
GenomeRNAii9447
PROiPR:O14862
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000163568 Expressed in 134 organ(s), highest expression level in small intestine Peyer's patch
CleanExiHS_AIM2
ExpressionAtlasiO14862 baseline and differential
GenevisibleiO14862 HS

Family and domain databases

InterProiView protein in InterPro
IPR004020 DAPIN
IPR011029 DEATH-like_dom_sf
IPR004021 HIN200/IF120x
PfamiView protein in Pfam
PF02760 HIN, 1 hit
PF02758 PYRIN, 1 hit
SMARTiView protein in SMART
SM01289 PYRIN, 1 hit
SUPFAMiSSF47986 SSF47986, 1 hit
PROSITEiView protein in PROSITE
PS50824 DAPIN, 1 hit
PS50834 HIN_200, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiAIM2_HUMAN
AccessioniPrimary (citable) accession number: O14862
Secondary accession number(s): A8K7M7, Q5T3V9, Q96FG9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: January 1, 1998
Last modified: November 7, 2018
This is version 140 of the entry and version 1 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. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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Main funding by: National Institutes of Health

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