Androgen receptor signaling pathway (Pan troglodytes)

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Negative regulatorsPositive regulatorsAndrogen Receptor Signaling PathwayAndrogenNUPIAS3FKBP4MYST2SMAD3SP1NCOR2SMARCE1SIN3ADAXXBMFZNF318RAD9ARNF6PIK3R2HDAC1PAK6EFCAB6PARK7RHOASMAD4ROCK1Actin polymerizationPPAP2ANR2C2BAG1STUB1STAT3RHOBCDKN1AARFOXO1NCOR1RB1KLK3PRDX1KAT2BRLN1CDC42LIMK2PATZ1MDM2PSMC3IPSUMO1LOC458308PTK2PIAS1LOC741907CARM1UBE3ACREB1RELAZMIZ1EGFRTGIF1SIRT1ROCK2KDM1ARUNX2DSTNAESARPPPGTPPPETV5NR0B2CAV1SRCPNCOA1RANRNF14PIAS4FLNAEP300CTNNB1GNB2L1CALRPIK3R1PAKT1PPTENARPUBE2IPIAS2ARBRCA1CCND1FHL2CREBBPNCOA4JUNNCOA2LOC100616510TGFB1I1ARCYAndrogenAndrogenARAndrogenKAT5CCNE1LOC461077Protein - 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, you must cite 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 83% conversion rate.

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Ontology Terms

 

Bibliography

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History

View all...
CompareRevisionActionTimeUserComment
78369view10:19, 7 January 2015MaintBotadded missing graphIds
71674view19:41, 17 October 2013MaintBotAutomated update of data sources
69267view18:38, 8 July 2013MaintBotUpdated to 2013 gpml schema
67047view09:59, 26 June 2013Christine ChichesterOntology Term : 'androgen signaling pathway' added !
48149view18:42, 9 May 2012MaintBotUpdating from human to fix xrefs
41575view02:00, 2 March 2011MaintBotRemoved redundant pathway information and comments
35683view22:53, 12 February 2010AlexanderPico
35679view22:50, 12 February 2010AlexanderPicoadding description and refs
34303view22:06, 9 December 2009MaintBotAutomatic update of empty xrefs
31586view22:04, 13 August 2009MaintBotFixed text labels
30466view21:30, 29 July 2009MaintBotNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
AESProtein744806 (Entrez Gene)
AKT1Protein
ARProtein747460 (Entrez Gene)
Actin polymerizationProtein
BAG1Protein465041 (Entrez Gene)
BMFRna90427 (Entrez Gene)
BRCA1Protein449497 (Entrez Gene)
CALRProtein455756 (Entrez Gene)
CARM1Protein
CAV1Protein463670 (Entrez Gene)
CCND1Protein
CCNE1Protein455914 (Entrez Gene)
CDC42Protein
CDKN1ARna1026 (Entrez Gene)
CREB1Protein459901 (Entrez Gene)
CREBBPProtein467891 (Entrez Gene)
CTNNB1Protein450183 (Entrez Gene)
DAXXProtein462613 (Entrez Gene)
DSTNProtein458108 (Entrez Gene)
EFCAB6Protein458892 (Entrez Gene)
EGFRProtein463415 (Entrez Gene)
EP300Protein
ETV5Protein460906 (Entrez Gene)
FHL2Protein459469 (Entrez Gene)
FKBP4Protein451748 (Entrez Gene)
FLNAProtein
FOXO1Protein467352 (Entrez Gene)
GNB2L1Protein462344 (Entrez Gene)
HDAC1Protein
JUNProtein456893 (Entrez Gene)
KAT2BProtein460219 (Entrez Gene)
KAT5Protein451329 (Entrez Gene)
KDM1AProtein456614 (Entrez Gene)
KLK3Rna354 (Entrez Gene)
LIMK2Protein458970 (Entrez Gene)
LOC100616510Protein100616510 (Entrez Gene)
LOC458308Protein458308 (Entrez Gene)
LOC461077Protein461077 (Entrez Gene)
LOC741907Protein741907 (Entrez Gene)
MDM2Protein742141 (Entrez Gene)
MYST2Protein455108 (Entrez Gene)
NCOA1Protein459068 (Entrez Gene)
NCOA2Protein464226 (Entrez Gene)
NCOA4Protein450455 (Entrez Gene)
NCOR1Protein468370 (Entrez Gene)
NCOR2Protein
NR0B2Protein737687 (Entrez Gene)
NR2C2Protein460199 (Entrez Gene)
PAK6Protein453327 (Entrez Gene)
PARK7Protein746063 (Entrez Gene)
PATZ1Protein470184 (Entrez Gene)
PIAS1Protein467715 (Entrez Gene)
PIAS2Protein
PIAS3Protein
PIAS4Protein
PIK3R1Protein461836 (Entrez Gene)
PIK3R2Protein455855 (Entrez Gene)
PPAP2ARna8611 (Entrez Gene)
PRDX1Protein456537 (Entrez Gene)
PSMC3IPProtein742143 (Entrez Gene)
PTENProtein466142 (Entrez Gene)
PTK2Protein464422 (Entrez Gene) DHT and testosterone induces phosphorylation of FAK in LNCaP cells.
RAD9AProtein
RANProtein452414 (Entrez Gene)
RB1Protein452715 (Entrez Gene)
RELAProtein466665 (Entrez Gene)
RHOAProtein461014 (Entrez Gene)
RHOBProtein459054 (Entrez Gene)
RLN1Rna
RNF14Protein471678 (Entrez Gene)
RNF6Protein452499 (Entrez Gene)
ROCK1Protein455326 (Entrez Gene)
ROCK2Protein470307 (Entrez Gene)
RUNX2Protein472017 (Entrez Gene)
SIN3AProtein
SIRT1Protein466088 (Entrez Gene)
SMAD3Protein748161 (Entrez Gene)
SMAD4Protein468537 (Entrez Gene)
SMARCE1Protein454655 (Entrez Gene)
SP1Protein451939 (Entrez Gene)
SRCProtein458229 (Entrez Gene)
STAT3Protein454682 (Entrez Gene)
STUB1Protein453803 (Entrez Gene)
SUMO1Protein459882 (Entrez Gene)
TGFB1I1Protein467962 (Entrez Gene)
TGIF1Protein
UBE2IProtein749975 (Entrez Gene)
UBE3AProtein453269 (Entrez Gene)
ZMIZ1Protein466119 (Entrez Gene)
ZNF318Protein462712 (Entrez Gene)

Annotated Interactions

No annotated interactions
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