Androgen receptor signaling pathway (Homo sapiens)

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1Negative regulatorsPositive regulatorsAndrogen receptor signaling pathwayActin polymerizationAndrogenNUPTK2RAD9ACDC42ARSP1KAT2BDAXXFOXO1KDM1ATGIF1RAC1NCOR1PARK7ZMIZ1EGFRBMFBAG1RHOBKLK3DSTNPAK6PIAS3UBE3ARELAPRDX1RHOAROCK1EFCAB6RNF6NCOR2PIK3R2STUB1ARSMAD4STAT3TZFMYST2NCOA3NR2C2SIRT1FKBP4PIAS1SMARCE1RUNX2PPAP2AMDM2SUMO1HDAC1SIN3APATZ1LIMK2SMAD3RB1PSMC3IPROCK2AESRLN1CDKN1ACARM1CREB1PPGTPPPPETV5NR0B2CAV1SRCPNCOA1RANRNF14PIAS4FLNAEP300CTNNB1GNB2L1CALRPIK3R1PAKT1PPTENARPUBE2IPIAS2ARBRCA1CCND1FHL2CREBBPNCOA4JUNNCOA2GSK3BTGFB1I1ARCYAndrogenAndrogenARAndrogenKAT5CCNE1RNF4Protein - 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


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 vesicle, 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 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.

Proteins on this pathway have targeted assays available via the CPTAC Assay Portal

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  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


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122133view12:51, 13 March 2022Ted23Modified description
120688view12:32, 23 December 2021EweitzStandardize font, weight, case
115904view09:19, 20 March 2021EgonwCopied the NetPath paper into the literature list
115899view08:07, 20 March 2021EgonwModified description
108320view20:48, 6 December 2019L DupuisConverted interactions to graphical lines in legend
105881view04:52, 16 August 2019KhanspersModified description
105528view06:00, 9 August 2019KhanspersModified description
79958view12:55, 28 April 2015ZariChanged label for Actin polymerization because it is process not protein
79277view21:48, 19 March 2015ZariAdded Identifier for TGIF1
78526view10:29, 7 January 2015MaintBotadded missing graphIds
72130view07:56, 25 October 2013Mkutmonadded datasource to SIN3A and PIAS2
71364view18:36, 17 October 2013MaintBotAutomated update of data sources
63142view19:17, 8 May 2013MaintBotUpdating GPML version
53243view19:04, 1 November 2012RobertbaertschAdd gene id to RLN1
47971view14:16, 23 April 2012NetPathModified description
47970view14:14, 23 April 2012NetPathModified description
44951view12:35, 6 October 2011MartijnVanIerselOntology Term : 'androgen signaling pathway' added !
44596view20:59, 21 September 2011KhanspersModified categories
44595view20:59, 21 September 2011KhanspersModified description
44594view20:58, 21 September 2011KhanspersUpdating content to NetSlim
44118view20:49, 24 August 2011KhanspersReverted to version '23:17, 1 March 2011' by Khanspers
44046view23:41, 22 August 2011KhanspersModified description
44045view23:39, 22 August 2011KhanspersUpdating pathway from NetSlim
41063view23:17, 1 March 2011MaintBotRemoved redundant pathway information and comments
35667view22:37, 12 February 2010AlexanderPicoModified description
35427view11:00, 12 February 2010AndraAdded references
35299view23:19, 11 February 2010NsalomonisModified description
20973view11:30, 14 November 2008MaintBot[[Pathway:Homo sapiens:Androgen-Receptor NetPath 2]] moved to [[Pathway:WP138]]: Moved to stable identifier
7902view13:46, 7 January 2008MaintBot[[Pathway:Human:Androgen-Receptor NetPath 2]] moved to [[Pathway:Homo sapiens:Androgen-Receptor NetPath 2]]: Renaming species
7576view16:01, 18 December 2007MaintBotfixed category names
7195view12:33, 4 November 2007MaintBotAdded categories to GPML
6294view22:17, 22 May 2007A.Pandeygpml file for [[Human:Androgen-Receptor_NetPath_2]]

External references


View all...
NameTypeDatabase referenceComment
AESProtein166 (Entrez Gene)
AKT1Protein207 (Entrez Gene)
ARProtein367 (Entrez Gene)
BAG1Protein573 (Entrez Gene)
BMFRna90427 (Entrez Gene)
BRCA1Protein672 (Entrez Gene)
CALRProtein811 (Entrez Gene)
CARM1Protein10498 (Entrez Gene)
CAV1Protein857 (Entrez Gene)
CCND1Protein595 (Entrez Gene)
CCNE1Protein898 (Entrez Gene)
CDC42Protein998 (Entrez Gene)
CDKN1ARna1026 (Entrez Gene)
CREB1Protein1385 (Entrez Gene)
CREBBPProtein1387 (Entrez Gene)
CTNNB1Protein1499 (Entrez Gene)
DAXXProtein1616 (Entrez Gene)
DSTNProtein11034 (Entrez Gene)
EFCAB6Protein64800 (Entrez Gene)
EGFRProtein1956 (Entrez Gene)
EP300Protein2033 (Entrez Gene)
ETV5Protein2119 (Entrez Gene)
FHL2Protein2274 (Entrez Gene)
FKBP4Protein2288 (Entrez Gene)
FLNAProtein2316 (Entrez Gene)
FOXO1Protein2308 (Entrez Gene)
GNB2L1Protein10399 (Entrez Gene)
GSK3BProtein2932 (Entrez Gene)
HDAC1Protein3065 (Entrez Gene)
JUNProtein3725 (Entrez Gene)
KAT2BProtein8850 (Entrez Gene)
KAT5Protein10524 (Entrez Gene)
KDM1AProtein23028 (Entrez Gene)
KLK3Rna354 (Entrez Gene)
LIMK2Protein3985 (Entrez Gene)
MDM2Protein4193 (Entrez Gene)
MYST2Protein11143 (Entrez Gene)
NCOA1Protein8648 (Entrez Gene)
NCOA2Protein10499 (Entrez Gene)
NCOA3Protein8202 (Entrez Gene)
NCOA4Protein8031 (Entrez Gene)
NCOR1Protein9611 (Entrez Gene)
NCOR2Protein9612 (Entrez Gene)
NR0B2Protein8431 (Entrez Gene)
NR2C2Protein7182 (Entrez Gene)
PAK6Protein56924 (Entrez Gene)
PARK7Protein11315 (Entrez Gene)
PATZ1Protein23598 (Entrez Gene)
PIAS1Protein8554 (Entrez Gene)
PIAS2Protein9063 (Entrez Gene)
PIAS3Protein10401 (Entrez Gene)
PIAS4Protein51588 (Entrez Gene)
PIK3R1Protein5295 (Entrez Gene)
PIK3R2Protein5296 (Entrez Gene)
PPAP2ARna8611 (Entrez Gene)
PRDX1Protein5052 (Entrez Gene)
PSMC3IPProtein29893 (Entrez Gene)
PTENProtein5728 (Entrez Gene)
PTK2Protein5747 (Entrez Gene) DHT and testosterone induces phosphorylation of FAK in LNCaP cells.
RAC1Protein5879 (Entrez Gene)
RAD9AProtein5883 (Entrez Gene)
RANProtein5901 (Entrez Gene)
RB1Protein5925 (Entrez Gene)
RELAProtein5970 (Entrez Gene)
RHOAProtein387 (Entrez Gene)
RHOBProtein388 (Entrez Gene)
RLN1GeneProduct6013 (Entrez Gene)
RNF14Protein9604 (Entrez Gene)
RNF4Protein6047 (Entrez Gene)
RNF6Protein6049 (Entrez Gene)
ROCK1Protein6093 (Entrez Gene)
ROCK2Protein9475 (Entrez Gene)
RUNX2Protein860 (Entrez Gene)
SIN3AProtein25942 (Entrez Gene)
SIRT1Protein23411 (Entrez Gene)
SMAD3Protein4088 (Entrez Gene)
SMAD4Protein4089 (Entrez Gene)
SMARCE1Protein6605 (Entrez Gene)
SP1Protein6667 (Entrez Gene)
SRCProtein6714 (Entrez Gene)
STAT3Protein6774 (Entrez Gene)
STUB1Protein10273 (Entrez Gene)
SUMO1Protein7341 (Entrez Gene)
TGFB1I1Protein7041 (Entrez Gene)
TGIF1Protein7050 (Entrez Gene)
TZFProtein24149 (Entrez Gene)
UBE2IProtein7329 (Entrez Gene)
UBE3AProtein7337 (Entrez Gene)
ZMIZ1Protein57178 (Entrez Gene)

Annotated Interactions

No annotated interactions

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