Androgen receptor signaling pathway (WP1014)

Bos taurus

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 [http://www.netpath.org/netslim/ar_pathway.html 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.

Authors

Alex Pico , Christine Chichester , Martina Summer-Kutmon , and Egon Willighagen

Activity

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Organisms

Bos taurus

Communities

Annotations

Pathway Ontology

androgen signaling pathway

Participants

Label Type Compact URI Comment
KDM1A Protein ensembl:ENSBTAG00000009500 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:23028
PIAS3 Protein ensembl:ENSBTAG00000021634 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:10401
SIRT1 Protein ensembl:ENSBTAG00000014023 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:23411
SMARCE1 Protein ensembl:ENSBTAG00000015308 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6605
RNF6 Protein ensembl:ENSBTAG00000005318 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6049
NR2C2 Protein ensembl:ENSBTAG00000013716 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7182
RAD9A Protein ensembl:ENSBTAG00000012141 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5883
RHOA Protein ensembl:ENSBTAG00000004279 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:387
RHOB Protein ensembl:ENSBTAG00000046054 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:388
PSMC3IP Protein ensembl:ENSBTAG00000020907 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:29893
SMAD4 Protein ensembl:ENSBTAG00000006919 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4089
FKBP4 Protein ensembl:ENSBTAG00000007605 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2288
NCOR2 Protein ensembl:ENSBTAG00000024603 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:9612
PIAS1 Protein ensembl:ENSBTAG00000005564 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8554
SUMO1 Protein ensembl:ENSBTAG00000009859 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7341
AR Protein ensembl:ENSBTAG00000022255 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:367
RUNX2 Protein ensembl:ENSBTAG00000004104 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:860
RAC1 Protein ensembl:ENSBTAG00000009233 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5879
PRDX1 Protein ensembl:ENSBTAG00000003642 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5052
PCAF Protein ensembl:ENSBTAG00000000746 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8850
CDC42 Protein ensembl:ENSBTAG00000001700 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:998
NCOR1 Protein ensembl:ENSBTAG00000013271 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:9611
STAT3 Protein ensembl:ENSBTAG00000021523 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6774
ROCK1 Protein ensembl:ENSBTAG00000008403 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6093
EGFR Protein ensembl:ENSBTAG00000011628 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1956
HDAC1 Protein ensembl:ENSBTAG00000012698 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3065
CREB1 Protein ensembl:ENSBTAG00000005474 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1385
FOXO1 Protein ensembl:ENSBTAG00000044105 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2308
MYST2 Protein ensembl:ENSBTAG00000018699 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:11143
SIN3A Protein ensembl:ENSBTAG00000009985 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:25942
DSTN Protein ensembl:ENSBTAG00000015434 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:11034
RB1 Protein ensembl:ENSBTAG00000006640 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5925
AES Protein ensembl:ENSBTAG00000031363 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:166
CARM1 Protein ensembl:ENSBTAG00000012048 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:10498
PATZ1 Protein ensembl:ENSBTAG00000005478 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:23598
TGIF1 Protein ensembl:ENSBTAG00000007718 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7050
NCOA3 Protein ensembl:ENSBTAG00000007489 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8202
ZNF318 Protein ensembl:ENSBTAG00000010217 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:24149
SMAD3 Protein ensembl:ENSBTAG00000012599 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4088
PARK7 Protein ensembl:ENSBTAG00000020518 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:11315
ZMIZ1 Protein ensembl:ENSBTAG00000019313 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:57178
EFCAB6 Protein ensembl:ENSBTAG00000030189 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:64800
DAXX Protein ensembl:ENSBTAG00000016830 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1616
RELA Protein ensembl:ENSBTAG00000013895 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5970
BAG1 Protein ensembl:ENSBTAG00000017845 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:573
LIMK2 Protein ensembl:ENSBTAG00000010662 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3985
MDM2 Protein ensembl:ENSBTAG00000010422 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4193
STUB1 Protein ensembl:ENSBTAG00000019136 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:10273
SP1 Protein ensembl:ENSBTAG00000003021 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6667
ROCK2 Protein ensembl:ENSBTAG00000005847 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:9475
PTK2 Protein ensembl:ENSBTAG00000009578 DHT and testosterone induces phosphorylation of FAK in LNCaP cells.
HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5747
PAK6 Protein ensembl:ENSBTAG00000019076 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:56924
UBE3A Protein ensembl:ENSBTAG00000002487 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7337
ETV5 Protein ensembl:ENSBTAG00000014915 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2119
NR0B2 Protein ensembl:ENSBTAG00000014848 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8431
CAV1 Protein ensembl:ENSBTAG00000017869 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:857
SRC Protein ensembl:ENSBTAG00000008938 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6714
NCOA1 Protein ensembl:ENSBTAG00000015007 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8648
RAN Protein ensembl:ENSBTAG00000014223 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5901
RNF14 Protein ensembl:ENSBTAG00000005249 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:9604
PIAS4 Protein ensembl:ENSBTAG00000000753 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:51588
FLNA Protein ensembl:ENSBTAG00000011190 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2316
EP300 Protein ensembl:ENSBTAG00000016198 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2033
CTNNB1 Protein ensembl:ENSBTAG00000016420 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1499
GNB2L1 Protein ensembl:ENSBTAG00000019648 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:10399
CALR Protein ensembl:ENSBTAG00000015114 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:811
PIK3R1 Protein ensembl:ENSBTAG00000010989 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5295
AKT1 Protein ensembl:ENSBTAG00000017636 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:207
PTEN Protein ensembl:ENSBTAG00000009498 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5728
UBE2I Protein ensembl:ENSBTAG00000038866 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7329
PIAS2 Protein ensembl:ENSBTAG00000007833 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:9063
BRCA1 Protein ensembl:ENSBTAG00000022520 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:672
CCND1 Protein ensembl:ENSBTAG00000017514 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:595
FHL2 Protein ensembl:ENSBTAG00000001086 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2274
CREBBP Protein ensembl:ENSBTAG00000026403 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1387
NCOA4 Protein ensembl:ENSBTAG00000019565 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8031
JUN Protein ensembl:ENSBTAG00000004037 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3725
NCOA2 Protein ensembl:ENSBTAG00000020312 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:10499
GSK3B Protein ensembl:ENSBTAG00000048057 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2932
TGFB1I1 Protein ensembl:ENSBTAG00000002391 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7041
KAT5 Protein ensembl:ENSBTAG00000005578 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:10524
CCNE1 Protein ensembl:ENSBTAG00000004735 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:898
RNF4 Protein ensembl:ENSBTAG00000027453 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6047

References

  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