Androgen receptor signaling pathway (WP1133)

Canis familiaris

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.


Alex Pico , Christine Chichester , and Egon Willighagen


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Canis familiaris



Pathway Ontology

androgen signaling pathway


Label Type Compact URI Comment
KDM1A Protein ncbigene:478193
PIAS3 Protein ncbigene:483160
SIRT1 Protein ncbigene:489012
SMARCE1 Protein ncbigene:608250
RNF6 Protein ncbigene:477332
NR2C2 Protein ncbigene:484641
RAD9A Protein ncbigene:483696
RHOA Protein ncbigene:403954
RHOB Protein ncbigene:403670
PSMC3IP Protein ncbigene:607659
SMAD4 Protein ncbigene:476196
FKBP4 Protein ncbigene:477726
NCOR2 Protein ncbigene:486242
PIAS1 Protein ncbigene:478350
SUMO1 Protein ncbigene:478874
AR Protein ncbigene:403588
RAC1 Protein ncbigene:403955
PRDX1 Protein ncbigene:475375
KAT2B Protein ncbigene:477052
CDC42 Protein ncbigene:403934
NCOR1 Protein ncbigene:479515
STAT3 Protein ncbigene:490967
ROCK1 Protein ncbigene:480181
EGFR Protein ncbigene:404306
HDAC1 Protein ncbigene:487309
PIK3R2 Protein ncbigene:609956
CREB1 Protein ncbigene:607922
FOXO1 Protein ncbigene:477295
KAT7 Protein ncbigene:491072
DSTN Protein ncbigene:477147
RB1 Protein ncbigene:476915
CARM1 Protein ncbigene:484947
PATZ1 Protein ncbigene:486365
NCOA3 Protein ncbigene:485915
ZNF318 Protein ncbigene:609493
SMAD3 Protein ncbigene:610902
PARK7 Protein ncbigene:479595
ZMIZ1 Protein ncbigene:489063
EFCAB6 Protein ncbigene:481218
DAXX Protein ncbigene:474873
RELA Protein ncbigene:483729
BAG1 Protein ncbigene:611781
LIMK2 Protein ncbigene:486363
AR Protein ncbigene:403588
MDM2 Protein ncbigene:403693
STUB1 Protein ncbigene:479892
SP1 Protein ncbigene:486507
ROCK2 Protein ncbigene:482970
PTK2 Protein ncbigene:475108 DHT and testosterone induces phosphorylation of FAK in LNCaP cells.
LOC100856038 Protein ncbigene:100856038
UBE3A Protein ncbigene:479010
ETV5 Protein ncbigene:607474
NR0B2 Protein ncbigene:612125
CAV1 Protein ncbigene:403980
SRC Protein ncbigene:485864
NCOA1 Protein ncbigene:475684
RAN Protein ncbigene:100499482
RNF14 Protein ncbigene:478042
PIAS4 Protein ncbigene:485049
FLNA Protein ncbigene:481084
EP300 Protein ncbigene:100684945
CTNNB1 Protein ncbigene:477032
CALR Protein ncbigene:476694
PIK3R1 Protein ncbigene:487235
AKT1 Protein ncbigene:490878
PTEN Protein ncbigene:403832
AR Protein ncbigene:403588
UBE2I Protein ncbigene:491332
AR Protein ncbigene:403588
BRCA1 Protein ncbigene:403437
CCND1 Protein ncbigene:449028
FHL2 Protein ncbigene:474544
CREBBP Protein ncbigene:479866
NCOA4 Protein ncbigene:477750
JUN Protein ncbigene:609429
NCOA2 Protein ncbigene:486989
GSK3B Protein ncbigene:478575
TGFB1I1 Protein ncbigene:489932
AR Protein ncbigene:403588
AR Protein ncbigene:403588
KAT5 Protein ncbigene:483728
CCNE1 Protein ncbigene:484610
RNF4 Protein ncbigene:610552


  1. NetPath: a public resource of curated signal transduction pathways. Kandasamy K, Mohan SS, Raju R, Keerthikumar S, Kumar GSS, Venugopal AK, et al. Genome Biol. 2010 Jan 12;11(1):R3. PubMed Europe PMC Scholia