Androgen receptor signaling pathway (Canis familiaris)

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Negative regulatorsPositive regulatorsAndrogenAndrogen Receptor Signaling PathwayNUSTAT3SMARCE1DAXXSUMO1ROCK2PIK3R2NCOR2RAC1CARM1LIMK2ROCK1SIN3APRDX1KDM1AKAT7ARCREB1NR2C2CDKN1APATZ1RAD9ARHOAKLK3NCOA3ARActin polymerizationZMIZ1SP1FKBP4RHOBDSTNAESSTUB1PTK2UBE3ALOC100856038MDM2ZNF318RELAFOXO1CDC42PIAS3PIAS1BAG1RUNX2SMAD3EGFRPSMC3IPRB1TGIF1SIRT1KAT2BBMFRNF6HDAC1NCOR1PPAP2AEFCAB6SMAD4RLN1PARK7GTPPPPPPETV5NR0B2CAV1SRCPNCOA1RANRNF14PIAS4FLNAEP300CTNNB1GNB2L1CALRPIK3R1PAKT1PPTENARPUBE2IPIAS2ARBRCA1CCND1FHL2CREBBPNCOA4JUNNCOA2GSK3BTGFB1I1ARCYAndrogenAndrogenARAndrogenKAT5CCNE1RNF4Protein - protein dissociationReceptorProteinEnzyme ComplexmRNAProteinProteinLigandSmall moleculeInduced activationInhibitionAuto catalysisTransportPositive regulation of gene expressionLeads to through unknown mechanismNegative regulation of gene expressionTranslocation UbiquitinationDeubiquitinationSumoylationInduced catalysisProtein-protein interactionAcetylationDephosphorylationLEGENDPhosphorylationDeacetylationGolgi apparatusEndosomeNucleusMitochondrionDesumoylationMethylationDemethylationPalmitoylationCytoplasmECPlasma membraneMTEndoplasmic reticulumCYPMGONUExtracellularERENProteolytic cleavageMolecule


Description

Androgens, mainly testosterone and 5alpha-dihydrotestosterone (DHT) play significant role in the growth and development of the male reproductive organs. These steroid hormones bring about their biological functions through their associations with Androgen receptor (AR), a 110 KDa ligand dependent transcription factor that falls under the group of nuclear receptor superfamily. DHT binds the receptor with high affinity compared to testosterone. The AR gene is located in the X chromosome at Xq11-12 site. AR is cytosolic protein, which in the ligand unbound state, is present as a complex with various Heat shock proteins primarily Hsp70, 90 and 56 as well as p23. Upon ligand binding, it dissociates from the complex. AR is found to be expressed in a number of tissues and cells including prostate, testis, seminal vescicle, epididymis, skin, skeletal muscle, cardiac muscle, liver and central nervous system. The protein has four functional domains- an N terminal domain (NTD), a DNA binding domain (DBD), a hinge region and a Ligand binding Domain (LBD). The DBD is a 658 amino acid residue region that has ZNF motifs which allows it bind to DNA. The rest of the domains are involved in dimerization and ligand binding. Two phosphorylation events are proposed to play very important role in the activation of the receptor upon ligand binding. The first phosphorylation event releases the ligand binding domain for hormone binding. The subsequent phosphorylation event is triggered upon hormone binding. Activated AR upon ligand binding undergoes conformational change to form a homodimer and interacts tightly with the Androgen Response Element (ARE). The androgen receptor is known to bind to many co-regulators at different time points and in different cell types. This DNA protein complex triggers the expression of various target genes that are associated with the male phenotype. Modulation of the AR activity is carried out by several transcription factors like ARA70, TR4, SRC family members and CBP/p300 and other associated proteins. FXXLF and WXXLF motifs containing coactivators such as the p160 members bind with the AF2 region of the Ligand Binding Domain of the AR. Androgen receptors are known to induce apoptosis under certain conditions. Various regulators that regulate androgen induced apoptosis include BRCA1 and Smad3 and Akt. Mutation in AR are also known to be associated in a number of diseases including spinal and bulbar muscular atrophy (SBMA) or Kennedy's disease and Androgen Insensitivity syndrome (AIS). Abnormal amplification of the androgen gene as well as deregulation of AR gene expression have been shown to be associated with prostate cancer.


Please access this pathway at NetSlim database.

If you use this pathway, please cite the following paper:

Kandasamy, K., Mohan, S. S., Raju, R., Keerthikumar, S., Kumar, G. S. S., Venugopal, A. K., Telikicherla, D., Navarro, J. D., Mathivanan, S., Pecquet, C., Gollapudi, S. K., Tattikota, S. G., Mohan, S., Padhukasahasram, H., Subbannayya, Y., Goel, R., Jacob, H. K. C., Zhong, J., Sekhar, R., Nanjappa, V., Balakrishnan, L., Subbaiah, R., Ramachandra, Y. L., Rahiman, B. A., Prasad, T. S. K., Lin, J., Houtman, J. C. D., Desiderio, S., Renauld, J., Constantinescu, S. N., Ohara, O., Hirano, T., Kubo, M., Singh, S., Khatri, P., Draghici, S., Bader, G. D., Sander, C., Leonard, W. J. and Pandey, A. (2010). NetPath: A public resource of curated signal transduction pathways. Genome Biology. 11:R3.

Comments

HomologyConvert 
This pathway was inferred from Homo sapiens pathway WP138(r47971) with a 92% conversion rate.

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Bibliography

  1. Kandasamy K, Mohan SS, Raju R, Keerthikumar S, Kumar GS, Venugopal AK, Telikicherla D, Navarro JD, Mathivanan S, Pecquet C, Gollapudi SK, Tattikota SG, Mohan S, Padhukasahasram H, Subbannayya Y, Goel R, Jacob HK, Zhong J, Sekhar R, Nanjappa V, Balakrishnan L, Subbaiah R, Ramachandra YL, Rahiman BA, Prasad TS, Lin JX, Houtman JC, Desiderio S, Renauld JC, Constantinescu SN, Ohara O, Hirano T, Kubo M, Singh S, Khatri P, Draghici S, Bader GD, Sander C, Leonard WJ, Pandey A; ''NetPath: a public resource of curated signal transduction pathways.''; Genome Biol, 2010 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
115921view17:01, 20 March 2021EgonwCopied the NetPath paper into the literature list
115916view15:31, 20 March 2021EgonwModified description
78442view10:26, 7 January 2015MaintBotadded missing graphIds
71482view19:18, 17 October 2013MaintBotAutomated update of data sources
68580view23:07, 5 July 2013MaintBotUpdated to 2013 gpml schema
67042view09:58, 26 June 2013Christine ChichesterOntology Term : 'androgen signaling pathway' added !
48158view18:53, 9 May 2012MaintBotUpdating from human to fix xrefs
40739view21:53, 1 March 2011MaintBotRemoved redundant pathway information and comments
35691view22:59, 12 February 2010AlexanderPico
35689view22:57, 12 February 2010AlexanderPicoadding description and refs
34014view18:43, 9 December 2009MaintBotAutomatic update of empty xrefs
32564view13:10, 17 August 2009MaintBotFixed text labels
31262view19:55, 13 August 2009MaintBotFixed text labels
30702view22:50, 29 July 2009MaintBotNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
AESProtein
AKT1Protein490878 (Entrez Gene)
ARProtein403588 (Entrez Gene)
Actin polymerizationProtein
BAG1Protein611781 (Entrez Gene)
BMFRna90427 (Entrez Gene)
BRCA1Protein403437 (Entrez Gene)
CALRProtein476694 (Entrez Gene)
CARM1Protein484947 (Entrez Gene)
CAV1Protein403980 (Entrez Gene)
CCND1Protein449028 (Entrez Gene)
CCNE1Protein484610 (Entrez Gene)
CDC42Protein403934 (Entrez Gene)
CDKN1ARna1026 (Entrez Gene)
CREB1Protein607922 (Entrez Gene)
CREBBPProtein479866 (Entrez Gene)
CTNNB1Protein477032 (Entrez Gene)
DAXXProtein474873 (Entrez Gene)
DSTNProtein477147 (Entrez Gene)
EFCAB6Protein481218 (Entrez Gene)
EGFRProtein404306 (Entrez Gene)
EP300Protein100684945 (Entrez Gene)
ETV5Protein607474 (Entrez Gene)
FHL2Protein474544 (Entrez Gene)
FKBP4Protein477726 (Entrez Gene)
FLNAProtein481084 (Entrez Gene)
FOXO1Protein477295 (Entrez Gene)
GNB2L1Protein
GSK3BProtein478575 (Entrez Gene)
HDAC1Protein487309 (Entrez Gene)
JUNProtein609429 (Entrez Gene)
KAT2BProtein477052 (Entrez Gene)
KAT5Protein483728 (Entrez Gene)
KAT7Protein491072 (Entrez Gene)
KDM1AProtein478193 (Entrez Gene)
KLK3Rna354 (Entrez Gene)
LIMK2Protein486363 (Entrez Gene)
LOC100856038Protein100856038 (Entrez Gene)
MDM2Protein403693 (Entrez Gene)
NCOA1Protein475684 (Entrez Gene)
NCOA2Protein486989 (Entrez Gene)
NCOA3Protein485915 (Entrez Gene)
NCOA4Protein477750 (Entrez Gene)
NCOR1Protein479515 (Entrez Gene)
NCOR2Protein486242 (Entrez Gene)
NR0B2Protein612125 (Entrez Gene)
NR2C2Protein484641 (Entrez Gene)
PARK7Protein479595 (Entrez Gene)
PATZ1Protein486365 (Entrez Gene)
PIAS1Protein478350 (Entrez Gene)
PIAS2Protein
PIAS3Protein483160 (Entrez Gene)
PIAS4Protein485049 (Entrez Gene)
PIK3R1Protein487235 (Entrez Gene)
PIK3R2Protein609956 (Entrez Gene)
PPAP2ARna8611 (Entrez Gene)
PRDX1Protein475375 (Entrez Gene)
PSMC3IPProtein607659 (Entrez Gene)
PTENProtein403832 (Entrez Gene)
PTK2Protein475108 (Entrez Gene) DHT and testosterone induces phosphorylation of FAK in LNCaP cells.
RAC1Protein403955 (Entrez Gene)
RAD9AProtein483696 (Entrez Gene)
RANProtein100499482 (Entrez Gene)
RB1Protein476915 (Entrez Gene)
RELAProtein483729 (Entrez Gene)
RHOAProtein403954 (Entrez Gene)
RHOBProtein403670 (Entrez Gene)
RLN1Rna
RNF14Protein478042 (Entrez Gene)
RNF4Protein610552 (Entrez Gene)
RNF6Protein477332 (Entrez Gene)
ROCK1Protein480181 (Entrez Gene)
ROCK2Protein482970 (Entrez Gene)
RUNX2Protein
SIN3AProtein
SIRT1Protein489012 (Entrez Gene)
SMAD3Protein610902 (Entrez Gene)
SMAD4Protein476196 (Entrez Gene)
SMARCE1Protein608250 (Entrez Gene)
SP1Protein486507 (Entrez Gene)
SRCProtein485864 (Entrez Gene)
STAT3Protein490967 (Entrez Gene)
STUB1Protein479892 (Entrez Gene)
SUMO1Protein478874 (Entrez Gene)
TGFB1I1Protein489932 (Entrez Gene)
TGIF1Protein
UBE2IProtein491332 (Entrez Gene)
UBE3AProtein479010 (Entrez Gene)
ZMIZ1Protein489063 (Entrez Gene)
ZNF318Protein609493 (Entrez Gene)

Annotated Interactions

No annotated interactions
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