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Protein

Interferon-inducible protein AIM2

Gene

AIM2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Enzyme 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

GO - Biological processi

  • activation of innate immune response Source: UniProtKB
  • apoptotic process Source: UniProtKB-KW
  • cellular response to drug Source: MGI
  • cellular response to interferon-beta Source: Ensembl
  • immune response Source: ProtInc
  • inflammatory response Source: UniProtKB-KW
  • innate immune response Source: UniProtKB-KW
  • interleukin-1 beta secretion Source: MGI
  • negative regulation of NF-kappaB transcription factor activity Source: UniProtKB
  • positive regulation of cysteine-type endopeptidase activity Source: UniProtKB
  • positive regulation of defense response to virus by host Source: UniProtKB
  • positive regulation of interleukin-1 beta production Source: UniProtKB
  • positive regulation of interleukin-1 beta secretion Source: UniProtKB
  • positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
  • positive regulation of protein oligomerization Source: UniProtKB
  • pyroptosis Source: UniProtKB
  • tumor necrosis factor-mediated signaling pathway Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Apoptosis, Immunity, Inflammatory response, Innate immunity

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000163568-MONOMER.
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

HGNCiHGNC:357. AIM2.

Subcellular locationi

  • Nucleus
  • Cytoplasm

  • Note: Activated inflammasomes can aggregate in the cytosol as speck-like particles.

GO - Cellular componenti

  • AIM2 inflammasome complex Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • nucleus Source: UniProtKB-SubCell
Complete GO annotation...

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.

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.
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 MAPRE1.8 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself3EBI-6253193,EBI-6253193
PYCARDQ9ULZ311EBI-6253193,EBI-751215

Protein-protein interaction databases

BioGridi114837. 2 interactors.
DIPiDIP-59741N.
IntActiO14862. 108 interactors.
STRINGi9606.ENSP00000357112.

Structurei

Secondary structure

1343
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi1 – 11Combined sources11
Helixi14 – 16Combined sources3
Helixi19 – 29Combined sources11
Turni30 – 32Combined sources3
Helixi37 – 40Combined sources4
Helixi45 – 56Combined sources12
Helixi58 – 71Combined sources14
Helixi75 – 91Combined sources17
Beta strandi148 – 150Combined sources3
Beta strandi154 – 161Combined sources8
Beta strandi165 – 169Combined sources5
Beta strandi172 – 182Combined sources11
Beta strandi187 – 192Combined sources6
Helixi195 – 199Combined sources5
Beta strandi206 – 214Combined sources9
Beta strandi219 – 221Combined sources3
Beta strandi225 – 229Combined sources5
Helixi240 – 247Combined sources8
Helixi252 – 256Combined sources5
Beta strandi263 – 275Combined sources13
Beta strandi277 – 286Combined sources10
Beta strandi289 – 296Combined sources8
Helixi300 – 302Combined sources3
Beta strandi309 – 319Combined sources11
Beta strandi321 – 327Combined sources7
Beta strandi333 – 337Combined sources5

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[»]
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
Contains 1 HIN-200 domain.PROSITE-ProRule annotation
Contains 1 pyrin domain.PROSITE-ProRule annotation

Phylogenomic databases

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

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
InterProiIPR004020. DAPIN.
IPR011029. DEATH-like_dom.
IPR004021. HIN200/IF120x.
[Graphical view]
PfamiPF02760. HIN. 1 hit.
PF02758. PYRIN. 1 hit.
[Graphical view]
SMARTiSM01289. PYRIN. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
PROSITEiPS50824. DAPIN. 1 hit.
PS50834. HIN_200. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

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 → K.1 PublicationCorresponds to variant rs2276405dbSNPEnsembl.1
Natural variantiVAR_043379304C → Y.1 PublicationCorresponds to variant rs778047649dbSNPEnsembl.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. Translation: CAI15088.1.
BC010940 mRNA. Translation: AAH10940.1. Frameshift.
CCDSiCCDS1181.1.
RefSeqiNP_004824.1. NM_004833.1.
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

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. Translation: CAI15088.1.
BC010940 mRNA. Translation: AAH10940.1. Frameshift.
CCDSiCCDS1181.1.
RefSeqiNP_004824.1. NM_004833.1.
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[»]
ProteinModelPortaliO14862.
SMRiO14862.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114837. 2 interactors.
DIPiDIP-59741N.
IntActiO14862. 108 interactors.
STRINGi9606.ENSP00000357112.

PTM databases

iPTMnetiO14862.
PhosphoSitePlusiO14862.

Polymorphism and mutation databases

BioMutaiAIM2.

Proteomic databases

MaxQBiO14862.
PaxDbiO14862.
PeptideAtlasiO14862.
PRIDEiO14862.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

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

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000163568-MONOMER.
ReactomeiR-HSA-844615. The AIM2 inflammasome.

Miscellaneous databases

GeneWikiiAIM2.
GenomeRNAii9447.
PROiO14862.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000163568.
CleanExiHS_AIM2.
ExpressionAtlasiO14862. baseline and differential.
GenevisibleiO14862. HS.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
InterProiIPR004020. DAPIN.
IPR011029. DEATH-like_dom.
IPR004021. HIN200/IF120x.
[Graphical view]
PfamiPF02760. HIN. 1 hit.
PF02758. PYRIN. 1 hit.
[Graphical view]
SMARTiSM01289. PYRIN. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
PROSITEiPS50824. DAPIN. 1 hit.
PS50834. HIN_200. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiAIM2_HUMAN
AccessioniPrimary (citable) accession number: O14862
Secondary accession number(s): A8K7M7, Q5T3V9, Q96FG9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: January 1, 1998
Last modified: November 2, 2016
This is version 128 of the entry and version 1 of the sequence. [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

Miscellaneous

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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.