Find AR Products |
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| Gene AR; Gene ANDR_Human |
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| Androgen receptor (dihydrotestosterone receptor; testicular feminization; spinal and bulbar muscular atrophy; Kennedy disease) |
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| NCBI/Entrez |
367 |
| HGNC |
644 |
| UniProt/Swiss-Prot/ UniProt/TrEMBL |
P10275 |
| Ensembl |
ENSG00000169083 |
| GDB |
120556 |
| OMIM |
313700 |
| GeneLoc |
GC0XP066680 |
| Synonyms: AIS, Androgen receptor, DHTR, Dihydrotestosterone receptor, HUMARA, KD, NR3C4, SBMA, SMAX1, TFM, Nuclear receptor subfamily 3 group C member 4 |
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Gene AR; Gene ANDR_Human
Androgen receptor, AR, a nuclear steroid hormone receptor (X-linked transcription factor) normally but not always activated by dihydrotestosterone (DHT), regulates secondary sexual differentiation in males and context-dependent cell survival or JNK kinase-dependent (MEKK1) apoptosis via coordinated trans-repression and trans-activation of gene activity. It is composed of three major domains; the amino-terminal domain (NTD), the DNA-binding domain (DBD) and the ligand-binding domain (LBD). AR can induce cellular differentiation or apoptosis in a context-dependent way. The study of AR in the context of prostrate cancer dependence/independence on DHT (androgen-dependence) and progression is an important area of research.
Androgen receptor, AR, DHTR, is a 98.9 kDa, 919 amino acids long protein coded by the AR gene ((Gene map locus Xq11.2-q12) that contains eleven c-Src kinase (CSK) tyrosine phosphorylation sites at Try223, Tyr267, Tyr307, Try346, Tyr357, Tyr362, Try363, Try393, Try543, Try551 and Try915. Dephosphorylation is cAMP-PKA-inducible phosphatase pathway-dependent. AR is activated by phosphorylation. Excess levels of phosphorylation have been associated with cancer progression. The AR is post-translationally modified on lysine residues by acetylation and sumoylation. AR is reversibly post-translationally modified by sumoylation (SUMO-1) at Lys386 and Lys520 by the conjugating enzyme Ubc9. Sumoylation of AR attenuates its trans-activation function. AR is acetylated on Lys630, Lys632 or Lys633 by the histone acetylase activites (HAT) of the cointegrator proteins p300 and CBP, CREB-binding protein, (PCAF). Acetylation of AR modulates its trans-activation activity and its MEKK1-dependent induction of apoptosis. Acetylation of AR has been linked to resistance to apoptosis and the promotion of prostrate cancer.
In addition to prostrate cancer, defects in AR have been linked to a number of other diseases including testicular feminization syndrome (TFM), X-linked spinal and bulbar muscular atrophy (SBMA) (Kennedy disease); infertility male syndrome (androgen insensitivity), and Reifenstein syndrome.
Sigma offers antibodies, shRNAs and other products useful for the study of the AR gene.
References:
Callewaert L, Verrijdt G, Haelens A, Claessens F. (2004) Differential effect of small ubiquitin-like modifier (SUMO)-ylation of the androgen receptor in the control of cooperativity on selective versus canonical response elements. Mol Endocrinol. 18: 1438-49.
Fu M, Wang C, Wang J, Zhang X, Sakamaki T, Yeung YG, Chang C, Hopp T, Fuqua SA, Jaffray E, Hay RT, Palvimo JJ, Jänne OA, Pestell RG. (2002) Androgen receptor acetylation governs trans activation and MEKK1-induced apoptosis without affecting in vitro sumoylation and trans-repression function. Mol Cell Biol. 22: 3373-88.
Fu M, Rao M, Wang C, Sakamaki T, Wang J, Di Vizio D, Zhang X, Albanese C, Balk S, Chang C, Fan S, Rosen E, Palvimo JJ, Jänne OA, Muratoglu S, Avantaggiati ML, Pestell RG. (2003) Acetylation of androgen receptor enhances coactivator binding and promotes prostate cancer cell growth. Mol Cell Biol. 23: 8563-75.
Lund A, Udd B, Juvonen V, Andersen PM, Cederquist K, Davis M, Gellera C, Kölmel C, Ronnevi LO, Sperfeld AD, Sörensen SA, Tranebjaerg L, Van Maldergem L, Watanabe M, Weber M, Yeung L, Savontaus ML. (2001) Multiple founder effects in spinal and bulbar muscular atrophy (SBMA, Kennedy disease) around the world. Eur J Hum Genet. 9: 431-6.
Nakao R, Yanase T, Sakai Y, Haji M, Nawata H. (1993) A single amino acid substitution (gly743 --> val) in the steroid-binding domain of the human androgen receptor leads to Reifenstein syndrome. J Clin Endocrinol Metab. 77: 103-7.
Poukka H, Karvonen U, Janne OA, Palvimo JJ. (2000) Covalent modification of the androgen receptor by small ubiquitin-like modifier 1 (SUMO-1). Proc Natl Acad Sci U S A. 97: 14145-50.
Yarbrough WG, Quarmby VE, Simental JA, Joseph DR, Sar M, Lubahn DB, Olsen KL, French FS, Wilson EM. (1990) A single base mutation in the androgen receptor gene causes androgen insensitivity in the testicular feminized rat. J Biol Chem. 265: 8893-900.
Footnote: Gene Data Sources: HGNC, Entrez Gene, UniProt/Swiss-Prot, UniProt/TrEMBL, GDB, OMIM, GeneLoc, Ensembl.
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