Toggle navigation
About
What is Reactome ?
News
Team
Scientific Advisory Board
Funding
Editorial Calendar
Release Calendar
Statistics
Our Logo
License Agreement
Privacy Notice
Disclaimer
Digital Preservation
Contact us
Content
Table of Contents
DOIs
Data Schema
Reactome Research Spotlight
ORCID Integration Project
COVID-19 Disease Pathways
Docs
Userguide
Pathway Browser
How do I search ?
Details Panel
Analysis Tools
Analysis Data
Analysis Gene Expression
Species Comparison
Tissue Distribution
Diseases
Cytomics
Review Status of Reactome Events
ReactomeFIViz
Developer's Zone
Graph Database
Analysis Service
Content Service
Pathways Overview
Pathway Diagrams
Icon Info
EHLD Specs & Guidelines
Icon Library Guidelines
Data Model
Curator Guide
Release Documentation
Computationally inferred events
FAQ
Linking to Us
Citing us
Tools
Pathway Browser
Analyse gene list
Analyse gene expression
Species Comparison
Tissue Distribution
Analysis Service
Content Service
ReactomeFIViz
Advanced Data Search
Site Search
Community
Contribute Pathway Knowledge
Icon Library
Outreach
Events
Publications
Partners
Contributors
Resources Guide
Download
About
What is Reactome ?
News
Team
Scientific Advisory Board
Funding
Editorial Calendar
Release Calendar
Statistics
Our Logo
License Agreement
Privacy Notice
Disclaimer
Digital Preservation
Contact us
Content
Table of Contents
DOIs
Data Schema
Reactome Research Spotlight
ORCID Integration Project
COVID-19 Disease Pathways
Docs
Userguide
Pathway Browser
How do I search ?
Details Panel
Analysis Tools
Analysis Data
Analysis Gene Expression
Species Comparison
Tissue Distribution
Diseases
Cytomics
Review Status of Reactome Events
ReactomeFIViz
Developer's Zone
Graph Database
Analysis Service
Content Service
Pathways Overview
Pathway Diagrams
Icon Info
EHLD Specs & Guidelines
Icon Library Guidelines
Data Model
Curator Guide
Release Documentation
Computationally inferred events
FAQ
Linking to Us
Citing us
Tools
Pathway Browser
Analyse gene list
Analyse gene expression
Species Comparison
Tissue Distribution
Analysis Service
Content Service
ReactomeFIViz
Advanced Data Search
Site Search
Community
Contribute Pathway Knowledge
Icon Library
Outreach
Events
Publications
Partners
Contributors
Resources Guide
Download
Search ...
Go!
FKBP1A binds sirolimus
Stable Identifier
R-HSA-9679044
Type
Reaction [binding]
Species
Homo sapiens
Compartment
cytosol
ReviewStatus
5/5
Locations in the PathwayBrowser
Expand all
Disease (Homo sapiens)
Infectious disease (Homo sapiens)
Viral Infection Pathways (Homo sapiens)
SARS-CoV Infections (Homo sapiens)
Potential therapeutics for SARS (Homo sapiens)
FKBP1A binds sirolimus (Homo sapiens)
Signal Transduction (Homo sapiens)
MTOR signalling (Homo sapiens)
mTORC1-mediated signalling (Homo sapiens)
FKBP1A binds sirolimus (Homo sapiens)
General
SBML
|
BioPAX
Level 2
Level 3
|
PDF
SVG
|
PNG
Low
Medium
High
|
PPTX
|
SBGN
Click the image above or
here
to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
Sirolimus is a macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to immunophilins. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties. Sirolimus inhibits T lymphocyte activation and proliferation that occurs in response to antigenic and cytokine (Interleukin IL-2, IL-4, and IL-15) stimulation by a mechanism that is distinct from that of other immunosuppressants. Sirolimus also inhibits antibody production. In cells, sirolimus binds to the immunophilin, peptidyl-prolyl cis-trans isomerase (FKBP1A, FKBP-12), to generate an immunosuppressive complex. The sirolimus:FKBP1A complex has no effect on calcineurin activity (Bierer et al. 1991). This complex binds to and inhibits the activation of the mammalian Target Of Rapamycin (mTOR), a key regulatory kinase. This inhibition suppresses cytokine-driven T-cell proliferation, inhibiting the progression from the G1 to the S phase of the cell cycle (Sehgal 1998, 2003).
Literature References
PubMed ID
Title
Journal
Year
9721431
Rapamune (RAPA, rapamycin, sirolimus): mechanism of action immunosuppressive effect results from blockade of signal transduction and inhibition of cell cycle progression
Sehgal, SN
Clin. Biochem.
1998
1715244
Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes
Lane, WS
,
Schreiber, SL
,
Friedman, J
,
Liu, J
,
Farmer, JD
,
Weissman, I
Cell
1991
12742462
Sirolimus: its discovery, biological properties, and mechanism of action
Sehgal, SN
Transplant. Proc.
2003
Participants
Input
FKBP1A [cytosol]
(Homo sapiens)
sirolimus [cytosol]
Output
FKBP1A:sirolimus [cytosol]
(Homo sapiens)
Participates
as an event of
Potential therapeutics for SARS (Homo sapiens)
mTORC1-mediated signalling (Homo sapiens)
Orthologous Events
FKBP1A binds sirolimus (Bos taurus)
FKBP1A binds sirolimus (Caenorhabditis elegans)
FKBP1A binds sirolimus (Canis familiaris)
FKBP1A binds sirolimus (Danio rerio)
FKBP1A binds sirolimus (Dictyostelium discoideum)
FKBP1A binds sirolimus (Drosophila melanogaster)
FKBP1A binds sirolimus (Gallus gallus)
FKBP1A binds sirolimus (Mus musculus)
FKBP1A binds sirolimus (Rattus norvegicus)
FKBP1A binds sirolimus (Saccharomyces cerevisiae)
FKBP1A binds sirolimus (Schizosaccharomyces pombe)
FKBP1A binds sirolimus (Sus scrofa)
FKBP1A binds sirolimus (Xenopus tropicalis)
Authored
Jassal, B (2020-03-23)
Reviewed
Shoichet, BK (2020-05-14)
Created
Jassal, B (2020-03-23)
© 2025
Reactome
Cite Us!
Cite Us!
Cite Us!
Warning!
Unable to extract citation. Please try again later.
Download As:
BibTeX
RIS
Text