InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: AR

Summary

InnateDB Protein

IDBP-238330.7

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Protein Name

androgen receptor

Synonyms

AIS; DHTR; HUMARA; HYSP1; KD; NR3C4; SBMA; SMAX1; TFM;

Species

Homo sapiens

Ensembl Protein

ENSP00000379358

InnateDB Gene

IDBG-73722 (AR)

Protein Structure

UniProt Annotation

Function

Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription factor activity is modulated by bound coactivator and corepressor proteins. Transcription activation is down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3. {ECO:0000269PubMed:14664718, ECO:0000269PubMed:15563469, ECO:0000269PubMed:17591767, ECO:0000269PubMed:17911242, ECO:0000269PubMed:18084323, ECO:0000269PubMed:19345326, ECO:0000269PubMed:20980437}.

Subcellular Localization

Nucleus. Cytoplasm. Note=Predominantly cytoplasmic in unligated form but translocates to the nucleus upon ligand-binding. Can also translocate to the nucleus in unligated form in the presence of GNB2L1.

Disease Associations

Androgen insensitivity syndrome (AIS) [MIM:300068]: An X- linked recessive form of pseudohermaphroditism due end-organ resistance to androgen. Affected males have female external genitalia, female breast development, blind vagina, absent uterus and female adnexa, and abdominal or inguinal testes, despite a normal 46,XY karyotype. {ECO:0000269PubMed:10022458, ECO:0000269PubMed:10221692, ECO:0000269PubMed:10221770, ECO:0000269PubMed:10404311, ECO:0000269PubMed:10458483, ECO:0000269PubMed:10571951, ECO:0000269PubMed:10590024, ECO:0000269PubMed:10690872, ECO:0000269PubMed:11587068, ECO:0000269PubMed:11744994, ECO:0000269PubMed:1307250, ECO:0000269PubMed:1316540, ECO:0000269PubMed:1426313, ECO:0000269PubMed:1430233, ECO:0000269PubMed:1464650, ECO:0000269PubMed:1480178, ECO:0000269PubMed:1487249, ECO:0000269PubMed:1569163, ECO:0000269PubMed:1609793, ECO:0000269PubMed:1775137, ECO:0000269PubMed:1999491, ECO:0000269PubMed:2082179, ECO:0000269PubMed:2594783, ECO:0000269PubMed:7537149, ECO:0000269PubMed:7581399, ECO:0000269PubMed:7633398, ECO:0000269PubMed:7641413, ECO:0000269PubMed:7671849, ECO:0000269PubMed:7929841, ECO:0000269PubMed:7962294, ECO:0000269PubMed:7970939, ECO:0000269PubMed:7981687, ECO:0000269PubMed:7981689, ECO:0000269PubMed:7993455, ECO:0000269PubMed:8040309, ECO:0000269PubMed:8096390, ECO:0000269PubMed:8103398, ECO:0000269PubMed:8162033, ECO:0000269PubMed:8224266, ECO:0000269PubMed:8281140, ECO:0000269PubMed:8325950, ECO:0000269PubMed:8413310, ECO:0000269PubMed:8446106, ECO:0000269PubMed:8626869, ECO:0000269PubMed:8647313, ECO:0000269PubMed:8683794, ECO:0000269PubMed:8723113, ECO:0000269PubMed:8768864, ECO:0000269PubMed:8809734, ECO:0000269PubMed:8830623, ECO:0000269PubMed:8918984, ECO:0000269PubMed:8990010, ECO:0000269PubMed:9001799, ECO:0000269PubMed:9007482, ECO:0000269PubMed:9039340, ECO:0000269PubMed:9106550, ECO:0000269PubMed:9160185, ECO:0000269PubMed:9252933, ECO:0000269PubMed:9255042, ECO:0000269PubMed:9302173, ECO:0000269PubMed:9328206, ECO:0000269PubMed:9544375, ECO:0000269PubMed:9554754, ECO:0000269PubMed:9610419, ECO:0000269PubMed:9627582, ECO:0000269PubMed:9698822, ECO:0000269PubMed:9788719, ECO:0000269PubMed:9851768, ECO:0000269PubMed:9856504, ECO:0000269Ref.107, ECO:0000269Ref.173}. Note=The disease is caused by mutations affecting the gene represented in this entry.Spinal and bulbar muscular atrophy X-linked 1 (SMAX1) [MIM:313200]: An X-linked recessive form of spinal muscular atrophy. Spinal muscular atrophy refers to a group of neuromuscular disorders characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. SMAX1 occurs only in men. Age at onset is usually in the third to fifth decade of life, but earlier involvement has been reported. It is characterized by slowly progressive limb and bulbar muscle weakness with fasciculations, muscle atrophy, and gynecomastia. The disorder is clinically similar to classic forms of autosomal spinal muscular atrophy. {ECO:0000269PubMed:15851746}. Note=The disease is caused by mutations affecting the gene represented in this entry. Caused by trinucleotide CAG repeat expansion. In SMAX1 patients the number of Gln ranges from 38 to 62. Longer expansions result in earlier onset and more severe clinical manifestations of the disease.Note=Defects in AR may play a role in metastatic prostate cancer. The mutated receptor stimulates prostate growth and metastases development despite of androgen ablation. This treatment can reduce primary and metastatic lesions probably by inducing apoptosis of tumor cells when they express the wild-type receptor.Androgen insensitivity, partial (PAIS) [MIM:312300]: A disorder that is characterized by hypospadias, hypogonadism, gynecomastia, genital ambiguity, normal XY karyotype, and a pedigree pattern consistent with X-linked recessive inheritance. Some patients present azoospermia or severe oligospermia without other clinical manifestations. {ECO:0000269PubMed:10022458, ECO:0000269PubMed:10221692, ECO:0000269PubMed:10470409, ECO:0000269PubMed:10502786, ECO:0000269PubMed:10543676, ECO:0000269PubMed:11587068, ECO:0000269PubMed:1303262, ECO:0000269PubMed:1307250, ECO:0000269PubMed:1316540, ECO:0000269PubMed:1424203, ECO:0000269PubMed:1430233, ECO:0000269PubMed:2010552, ECO:0000269PubMed:7581399, ECO:0000269PubMed:7649358, ECO:0000269PubMed:7671849, ECO:0000269PubMed:7909256, ECO:0000269PubMed:7910529, ECO:0000269PubMed:7929841, ECO:0000269PubMed:7970939, ECO:0000269PubMed:7981687, ECO:0000269PubMed:8033918, ECO:0000269PubMed:8097257, ECO:0000269PubMed:8126121, ECO:0000269PubMed:8205256, ECO:0000269PubMed:8281139, ECO:0000269PubMed:8325932, ECO:0000269PubMed:8325950, ECO:0000269PubMed:8446106, ECO:0000269PubMed:8550758, ECO:0000269PubMed:8809734, ECO:0000269PubMed:8823308, ECO:0000269PubMed:8824883, ECO:0000269PubMed:9039340, ECO:0000269PubMed:9196614, ECO:0000269PubMed:9302173, ECO:0000269PubMed:9329414, ECO:0000269PubMed:9543136, ECO:0000269PubMed:9607727, ECO:0000269PubMed:9768671, ECO:0000269PubMed:9856504, ECO:0000269Ref.115}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Isoform 2 is mainly expressed in heart and skeletal muscle. {ECO:0000269PubMed:15634333}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 453 experimentally validated interaction(s) in this database.
They are also associated with 18 interaction(s) predicted by orthology.

Experimentally validated
Total	453 [view]
Protein-Protein	433 [view]
Protein-DNA	15 [view]
Protein-RNA	0
DNA-DNA	5 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	18 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000978	RNA polymerase II core promoter proximal region sequence-specific DNA binding
GO:0001077	RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription
GO:0001085	RNA polymerase II transcription factor binding
GO:0003677	DNA binding
GO:0003682	chromatin binding
GO:0003700	sequence-specific DNA binding transcription factor activity
GO:0003707	steroid hormone receptor activity
GO:0004879	ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity
GO:0004882	androgen receptor activity
GO:0005102	receptor binding
GO:0005497	androgen binding
GO:0005515	protein binding
GO:0008013	beta-catenin binding
GO:0008134	transcription factor binding
GO:0008270	zinc ion binding
GO:0019899	enzyme binding
GO:0043565	sequence-specific DNA binding
GO:0044212	transcription regulatory region DNA binding
GO:0046983	protein dimerization activity

Biological Process

GO:0006351	transcription, DNA-templated
GO:0006355	regulation of transcription, DNA-templated
GO:0006367	transcription initiation from RNA polymerase II promoter
GO:0006810	transport
GO:0007165	signal transduction
GO:0007267	cell-cell signaling
GO:0007548	sex differentiation
GO:0008219	cell death
GO:0008283	cell proliferation
GO:0008284	positive regulation of cell proliferation
GO:0010467	gene expression
GO:0016049	cell growth
GO:0030521	androgen receptor signaling pathway
GO:0030522	intracellular receptor signaling pathway
GO:0030850	prostate gland development
GO:0042327	positive regulation of phosphorylation
GO:0043401	steroid hormone mediated signaling pathway
GO:0045720	negative regulation of integrin biosynthetic process
GO:0045726	positive regulation of integrin biosynthetic process
GO:0045893	positive regulation of transcription, DNA-templated
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0045945	positive regulation of transcription from RNA polymerase III promoter
GO:0051092	positive regulation of NF-kappaB transcription factor activity
GO:0051259	protein oligomerization
GO:0090003	regulation of establishment of protein localization to plasma membrane
GO:2001237	negative regulation of extrinsic apoptotic signaling pathway

Cellular Component

GO:0000790	nuclear chromatin
GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005737	cytoplasm
GO:0043234	protein complex

Protein Structure and Domains

PDB ID

InterPro

IPR000536 Nuclear hormone receptor, ligand-binding, core
IPR001628 Zinc finger, nuclear hormone receptor-type
IPR001723 Steroid hormone receptor
IPR008946 Nuclear hormone receptor, ligand-binding

PFAM

PF00104
PF00105

PRINTS

PR00047
PR00398

PIRSF

SMART

SM00430
SM00399

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt