Pathways of nucleic acid metabolism and innate immune sensing (Homo sapiens)

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DegradationNucleusUV lightDNA sensing pathway led by cGASLysosomeType I IFN activiationDNAreplicationDNA damageRNA degradationNucleotideexcision repairByproducts of DNA repairRibonucleotideexcision repairdsRNARNase T2SAMHD1IFIH1DDX58IFNBdNTP poolsSTINGmRNADNARetroelement1TMEM173RNase H2subunit ATREX1AdenosineOAS1dsDNARNase LADAR2, 3Type I signallingcGASMAVSIRF3cDNAMDA5RIG-IdNssDNAssDNADNARTTRNase H2subunit BRNase H2subunit CDNARssDNAssDNASAMHD1dsRNAAdsRNAIdsRNAInosineshortdsRNAfragmentsRNA sensing pathways led by MDA5 and RIG-IIRF3PISGsType II signallingrRNA


Description

Cytosolic DNA and RNA can lead to innate immune sensing via three paths. DNA is sensed by cGAS, which activates STING.

RNA is sensed by MDA5 and RIG-I, which activates MAVS. An activation of STING or MAVS lead to phosphorylation of IFR3, which triggers innate immune responses.

This pathway was inspired by Chapter 14 of the 5th edition of the book of Blau (in press).

Quality Tags

Ontology Terms

 

Bibliography

  1. Deininger PL, Batzer MA; ''Mammalian retroelements.''; Genome Res, 2002 PubMed Europe PMC
  2. Patterson JB, Samuel CE; ''''; , PubMed Europe PMC
  3. Cho DS, Yang W, Lee JT, Shiekhattar R, Murray JM, Nishikura K; ''Requirement of dimerization for RNA editing activity of adenosine deaminases acting on RNA.''; J Biol Chem, 2003 PubMed Europe PMC

History

View all...
CompareRevisionActionTimeUserComment
107300view12:13, 19 September 2019DeSlModified description
107299view12:12, 19 September 2019DeSlAdded missing IDs
107298view12:06, 19 September 2019DeSlOntology Term : 'altered DNA repair pathway' added !
107297view12:06, 19 September 2019DeSlOntology Term : 'signaling pathway in the innate immune response' added !
107296view12:05, 19 September 2019DeSlModified description
107295view12:00, 19 September 2019DeSlAdded rRNA part
107294view11:50, 19 September 2019DeSlAdded background colours, added Lysosome
107293view11:43, 19 September 2019DeSlAdded IFNB and ISGs
107291view11:37, 19 September 2019DeSlAdded phosphorylation of the transcription factor interferon regulatory factor 3 (IRF3)
107290view11:33, 19 September 2019DeSlCompleted right hand side of PW
107286view08:35, 19 September 2019DeSlAdded more details on dsRNA interaction with MDA5
107183view14:27, 17 September 2019MaintBotChEBI identifier normalization
106678view15:09, 16 September 2019DeSlAdded more details on NER and RER
106677view14:35, 16 September 2019DeSlNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ADARProteinP55265 (Uniprot-TrEMBL) Catalyzes the hydrolytic deamination of adenosine to inosine in double-stranded RNA (dsRNA) referred to as A-to-I RNA editing
AdenosineMetabolite74411 (ChEBI)
DDX58GeneProductENSG00000107201 (Ensembl)
DNA replicationPathwayWP466 (WikiPathways)
DNA sensing pathway led by cGASPathway
DNAQ7430 (Wikidata)
IFIH1GeneProductENSG00000115267 (Ensembl)
IFNBGeneProductENSG00000171855 (Ensembl)
IRF3ProteinQ14653 (Uniprot-TrEMBL)
ISGsProteinIPR000471 (InterPro) interferon-responsive genes
InosineMetabolite82852 (ChEBI)
MAVSProteinQ7Z434 (Uniprot-TrEMBL) mitochondrial antiviral signaling (MAVS)
MDA5ProteinQ9BYX4 (Uniprot-TrEMBL)
  • Cytosolic RNA sensor
  • Activating mutations in RIG-I and MDA5 increase receptor affinity resulting in constitutive type I IFN signaling.
Nucleotide

excision

repair
PathwayWP1980 (WikiPathways) The presence of ribonucleotides in genomic DNA enhances photodimerization of adjacent pyrimidines, which are repaired by nucleotide excision repair
OAS1ProteinP00973 (Uniprot-TrEMBL)
RIG-IProteinO95786 (Uniprot-TrEMBL)
  • cytosolic RNA sensor
  • Activating mutations in RIG-I and MDA5 increase receptor affinity resulting in constitutive type I IFN signaling.
RNA sensing pathways led by MDA5 and RIG-IPathway
RNase H2 subunit AProteinO75792 (Uniprot-TrEMBL) Catalytic subunit
RNase H2 subunit BProteinQ5TBB1 (Uniprot-TrEMBL) Noncatalytic subunit
RNase H2 subunit CProteinQ8TDP1 (Uniprot-TrEMBL) Noncatalytic subunit
RNase LProteinQ05823 (Uniprot-TrEMBL)
RNase T2ProteinO00584 (Uniprot-TrEMBL)
RetroelementQ1473344 (Wikidata)
SAMHD1ProteinQ9Y3Z3 (Uniprot-TrEMBL) SAMHD1 has also ribonuclease activity, suggesting that a loss of SAMHD1 may lead to RNA accumulation.
STINGProteinQ86WV6 (Uniprot-TrEMBL)
TMEM173GeneProductENSG00000184584 (Ensembl) cGAS which signals via STING (encoded by TMEM173)
TREX1ProteinQ9NSU2 (Uniprot-TrEMBL) Cytosolic deoxyribonuclease anchored in the outer nuclear membrane. A lack of TREX1 causes DNA accumulation, both within the nucleus and the cytosol.
Type I signallingPathwayWP585 (WikiPathways)
Type II signallingPathwayWP619 (WikiPathways)
cDNAQ283478 (Wikidata) Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase.
cGASProteinQ8N884 (Uniprot-TrEMBL) DNA sensor
dNMetaboliteCHEBI:18274 (ChEBI)
dNTP poolsMetaboliteCHEBI:46149 (ChEBI)
dsDNAQ55978910 (Wikidata)
dsRNAQ2819370 (Wikidata)
mRNAQ188928 (Wikidata)
rRNAQ215980 (Wikidata)
short

dsRNA

fragments
Q2819370 (Wikidata)
ssDNAQ10906438 (Wikidata) single-stranded DNA

Annotated Interactions

SourceTargetTypeDatabase referenceComment
dNTP poolsdNmim-conversion46149 (Rhea) SAMHD1 degrades deoxynucleoside triphosphates (dNTP)
dsRNAdsRNAmim-conversion10121 (Rhea) ADAR modifies dsRNA through deamination of adenosine to inosine
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