Androgen receptor signaling pathway (Bos taurus)

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Negative regulatorsPositive regulatorsAndrogen Receptor Signaling PathwayActin polymerizationAndrogenNUBAG1CARM1NCOA3HDAC1RUNX2RELAUBE3AKDM1AEFCAB6TGIF1ROCK1DAXXNR2C2PPAP2ARNF6DSTNSMAD3NCOR2MYST2STAT3PIK3R2PRDX1ZMIZ1STUB1NCOR1ARRB1SP1RHOABMFPATZ1SMARCE1FKBP4SIN3ALIMK2RAD9AAREGFRSMAD4SIRT1AESCDKN1AROCK2RLN1KLK3FOXO1PIAS1CREB1ZNF318PTK2CDC42PIAS3PCAFPSMC3IPPARK7SUMO1RAC1PAK6MDM2RHOBPPPPPGTPETV5NR0B2CAV1SRCPNCOA1RANRNF14PIAS4FLNAEP300CTNNB1GNB2L1CALRPIK3R1PAKT1PPTENARPUBE2IPIAS2ARBRCA1CCND1FHL2CREBBPNCOA4JUNNCOA2GSK3BTGFB1I1ARCYAndrogenAndrogenARAndrogenKAT5CCNE1RNF4Protein - 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(79958) with a 96.0% conversion rate.

Quality Tags

Ontology Terms

 

Bibliography

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History

View all...
CompareRevisionActionTimeUserComment
80748view15:24, 30 June 2015Mkutmonhomology conversion
78596view14:51, 7 January 2015MaintBotadded missing graphIds
71402view19:00, 17 October 2013MaintBotAutomated update of data sources
67041view09:58, 26 June 2013Christine ChichesterOntology Term : 'androgen signaling pathway' added !
63334view21:13, 9 May 2013MaintBotUpdated to 2013 gpml schema
48135view05:53, 9 May 2012MaintBotUpdating from human to fix xref duplication
40513view19:29, 1 March 2011MaintBotRemoved redundant pathway information and comments
35686view22:55, 12 February 2010AlexanderPico
35684view22:55, 12 February 2010AlexanderPicoadding description and refs
33756view00:00, 9 December 2009MaintBotAutomatic update of empty xrefs
32492view12:46, 17 August 2009MaintBotFixed text labels
31190view19:30, 13 August 2009MaintBotFixed text labels
30583view22:10, 29 July 2009MaintBotNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
AESProteinENSBTAG00000031363 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:166
AKT1ProteinENSBTAG00000017636 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:207
ARProteinENSBTAG00000022255 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:367
BAG1ProteinENSBTAG00000017845 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:573
BMFRnaENSBTAG00000012180 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:90427
BRCA1ProteinENSBTAG00000022520 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:672
CALRProteinENSBTAG00000015114 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:811
CARM1ProteinENSBTAG00000012048 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:10498
CAV1ProteinENSBTAG00000017869 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:857
CCND1ProteinENSBTAG00000017514 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:595
CCNE1ProteinENSBTAG00000004735 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:898
CDC42ProteinENSBTAG00000001700 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:998
CDKN1ARnaENSBTAG00000008353 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1026
CREB1ProteinENSBTAG00000005474 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1385
CREBBPProteinENSBTAG00000026403 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1387
CTNNB1ProteinENSBTAG00000016420 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1499
DAXXProteinENSBTAG00000016830 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1616
DSTNProteinENSBTAG00000015434 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:11034
EFCAB6ProteinENSBTAG00000030189 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:64800
EGFRProteinENSBTAG00000011628 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1956
EP300ProteinENSBTAG00000016198 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2033
ETV5ProteinENSBTAG00000014915 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2119
FHL2ProteinENSBTAG00000001086 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2274
FKBP4ProteinENSBTAG00000007605 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2288
FLNAProteinENSBTAG00000011190 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2316
FOXO1ProteinENSBTAG00000044105 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2308
GNB2L1ProteinENSBTAG00000019648 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:10399
GSK3BProteinENSBTAG00000048057 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2932
HDAC1ProteinENSBTAG00000012698 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3065
JUNProteinENSBTAG00000004037 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3725
KAT5ProteinENSBTAG00000005578 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:10524
KDM1AProteinENSBTAG00000009500 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:23028
KLK3Rna
LIMK2ProteinENSBTAG00000010662 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3985
MDM2ProteinENSBTAG00000010422 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4193
MYST2ProteinENSBTAG00000018699 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:11143
NCOA1ProteinENSBTAG00000015007 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8648
NCOA2ProteinENSBTAG00000020312 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:10499
NCOA3ProteinENSBTAG00000007489 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8202
NCOA4ProteinENSBTAG00000019565 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8031
NCOR1ProteinENSBTAG00000013271 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:9611
NCOR2ProteinENSBTAG00000024603 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:9612
NR0B2ProteinENSBTAG00000014848 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8431
NR2C2ProteinENSBTAG00000013716 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7182
PAK6ProteinENSBTAG00000019076 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:56924
PARK7ProteinENSBTAG00000020518 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:11315
PATZ1ProteinENSBTAG00000005478 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:23598
PCAFProteinENSBTAG00000000746 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8850
PIAS1ProteinENSBTAG00000005564 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8554
PIAS2ProteinENSBTAG00000007833 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:9063
PIAS3ProteinENSBTAG00000021634 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:10401
PIAS4ProteinENSBTAG00000000753 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:51588
PIK3R1ProteinENSBTAG00000010989 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5295
PIK3R2ProteinHomologyConvert: Multiple homologues found: En:ENSBTAG00000002350;En:ENSBTAG00000002350;
PPAP2ARnaENSBTAG00000010526 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8611
PRDX1ProteinENSBTAG00000003642 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5052
PSMC3IPProteinENSBTAG00000020907 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:29893
PTENProteinENSBTAG00000009498 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5728
PTK2ProteinENSBTAG00000009578 (Ensembl)
  • DHT and testosterone induces phosphorylation of FAK in LNCaP cells.
  • HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5747
RAC1ProteinENSBTAG00000009233 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5879
RAD9AProteinENSBTAG00000012141 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5883
RANProteinENSBTAG00000014223 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5901
RB1ProteinENSBTAG00000006640 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5925
RELAProteinENSBTAG00000013895 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5970
RHOAProteinENSBTAG00000004279 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:387
RHOBProteinENSBTAG00000046054 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:388
RLN1GeneProduct
RNF14ProteinENSBTAG00000005249 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:9604
RNF4ProteinENSBTAG00000027453 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6047
RNF6ProteinENSBTAG00000005318 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6049
ROCK1ProteinENSBTAG00000008403 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6093
ROCK2ProteinENSBTAG00000005847 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:9475
RUNX2ProteinENSBTAG00000004104 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:860
SIN3AProteinENSBTAG00000009985 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:25942
SIRT1ProteinENSBTAG00000014023 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:23411
SMAD3ProteinENSBTAG00000012599 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4088
SMAD4ProteinENSBTAG00000006919 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4089
SMARCE1ProteinENSBTAG00000015308 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6605
SP1ProteinENSBTAG00000003021 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6667
SRCProteinENSBTAG00000008938 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6714
STAT3ProteinENSBTAG00000021523 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6774
STUB1ProteinENSBTAG00000019136 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:10273
SUMO1ProteinENSBTAG00000009859 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7341
TGFB1I1ProteinENSBTAG00000002391 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7041
TGIF1ProteinENSBTAG00000007718 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7050
UBE2IProteinENSBTAG00000038866 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7329
UBE3AProteinENSBTAG00000002487 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7337
ZMIZ1ProteinENSBTAG00000019313 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:57178
ZNF318ProteinENSBTAG00000010217 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:24149

Annotated Interactions

No annotated interactions
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