P19091 (ANDR_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Androgen receptor

Alternative name(s):
Dihydrotestosterone receptor
Nuclear receptor subfamily 3 group C member 4

Gene names

Name:	Ar
Synonyms:	Nr3c4

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	899 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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 By similarity.
Subunit structure	Binds DNA as a homodimer. Part of a ternary complex containing AR, EFCAB6/DJBP and PARK7. Interacts with HIPK3 and NR0B2 in the presence of androgen. The ligand binding domain interacts with KAT7/HBO1 in the presence of dihydrotestosterone. Interacts with EFCAB6/DJBP, PELP1, PQBP1, RANBP9, SPDEF, SRA1, TGFB1I1, ZNF318 and RREB1. The AR N-terminal poly-Gln region binds Ran resulting in enhancement of AR-mediated transactivation. Ran-binding decreases as the poly-Gln length increases. Interacts with ZMIZ1/ZIMP10 and ZMIZ2/ZMIP7 which both enhance its transactivation activity. Interacts with RBAK. Interacts via the ligand-binding domain with LXXLL and FXXLF motifs from NCOA1, NCOA2, NCOA3, NCOA4 and MAGEA11. Interacts with HIP1 (via coiled coil domain) By similarity. Interacts with SLC30A9 and RAD54L2/ARIP4. Interacts with MACROD1 By similarity. Interacts (via ligand-binding domain) with TRIM68 By similarity. Interacts with TNK2 By similarity. Interacts with USP26 By similarity. Interacts with RNF6 By similarity. Interacts (regulated by RNF6 probably through polyubiquitination) with RNF14; regulates AR transcriptional activity. Interacts with PRMT2 and TRIM24. Interacts with GNB2L1/RACK1 By similarity. Interacts with RANBP10; this interaction enhances hormone-induced AR transcriptional activity By similarity. Interacts with PRPF6 in a hormone-independent way; this interaction enhances hormone-induced AR transcriptional activity. Interacts with STK4/MST1 By similarity. Interacts with ZIPK/DAPK3 By similarity. Interacts with LPXN By similarity. Interacts with MAK By similarity. Part of a complex containing AR, MAK and NCOA3 By similarity. Ref.5 Ref.6 Ref.7 Ref.8
Subcellular location	Nucleus. Cytoplasm By similarity. 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 By similarity.
Domain	Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain. In the presence of bound steroid the ligand-binding domain interacts with the N-terminal modulating domain, and thereby activates AR transcription factor activity. Agonist binding is required for dimerization and binding to target DNA. The transcription factor activity of the complex formed by ligand-activated AR and DNA is modulated by interactions with coactivator and corepressor proteins. Interaction with RANBP9 is mediated by both the N-terminal domain and the DNA-binding domain. Interaction with EFCAB6/DJBP is mediated by the DNA-binding domain By similarity.
Post-translational modification	Phosphorylated in prostate cancer cells in response to several growth factors including EGF. Phosphorylation is induced by c-Src kinase (CSK). Tyr-514 is one of the major phosphorylation sites and an increase in phosphorylation and Src kinase activity is associated with prostate cancer progression By similarity. Phosphorylation by TNK2 enhances the DNA-binding and transcriptional activity. Phosphorylation at Ser-61 by CDK9 regulates AR promoter selectivity and cell growth. Phosphorylation by PAK6 leads to AR-mediated transcription inhibition By similarity. Sumoylated on Lys-381 (major) and Lys-500 By similarity. Ubiquitinated. Deubiquitinated by USP26 By similarity. 'Lys-6' and 'Lys-27'-linked polyubiquitination by RNF6 modulates AR transcriptional activity and specificity By similarity. Palmitoylated by ZDHHC7 and ZDHHC21. Palmitoylation is required for plasma membrane targeting and for rapid intracellular signaling via ERK and AKT kinases and cAMP generation By similarity.
Miscellaneous	In the absence of ligand, steroid hormone receptors are thought to be weakly associated with nuclear components; hormone binding greatly increases receptor affinity. The hormone-receptor complex appears to recognize discrete DNA sequences upstream of transcriptional start sites. Transcriptional activity is enhanced by binding to RANBP9.
Sequence similarities	Belongs to the nuclear hormone receptor family. NR3 subfamily. Contains 1 nuclear receptor DNA-binding domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Domain	Zinc-finger
Ligand	DNA-binding Lipid-binding Metal-binding Steroid-binding Zinc
Molecular function	Receptor
PTM	Isopeptide bond Lipoprotein Palmitate Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of prostate induction by androgen receptor signaling pathway Inferred from mutant phenotype PubMed 17317769. Source: MGI epithelial cell differentiation involved in prostate gland development Inferred from mutant phenotype PubMed 17652515. Source: MGI in utero embryonic development Inferred from mutant phenotype PubMed 10319319. Source: MGI lateral sprouting involved in mammary gland duct morphogenesis Inferred from mutant phenotype PubMed 14676301. Source: MGI male genitalia morphogenesis Inferred from mutant phenotype PubMed 19282366. Source: MGI male gonad development Inferred from mutant phenotype PubMed 10319319PubMed 17317769. Source: MGI male somatic sex determination Inferred from mutant phenotype PubMed 5452809. Source: MGI mammary gland alveolus development Inferred from mutant phenotype PubMed 14676301. Source: MGI morphogenesis of an epithelial fold Inferred from mutant phenotype PubMed 17652515. Source: MGI negative regulation of apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of epithelial cell proliferation Inferred from mutant phenotype PubMed 17652515. Source: MGI negative regulation of integrin biosynthetic process Inferred from sequence or structural similarity. Source: UniProtKB organ formation Inferred from mutant phenotype PubMed 17317769. Source: MGI positive regulation of MAPK cascade Inferred from mutant phenotype PubMed 14676301. Source: MGI positive regulation of NF-kappaB transcription factor activity Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of insulin-like growth factor receptor signaling pathway Inferred from mutant phenotype PubMed 14676301. Source: MGI positive regulation of integrin biosynthetic process Inferred from electronic annotation. Source: Compara positive regulation of intracellular estrogen receptor signaling pathway Inferred from mutant phenotype PubMed 14676301. Source: MGI positive regulation of phosphorylation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of transcription from RNA polymerase III promoter Inferred from electronic annotation. Source: Compara prostate gland epithelium morphogenesis Inferred from mutant phenotype PubMed 17652515. Source: MGI prostate gland growth Inferred from mutant phenotype PubMed 17317769PubMed 17652515. Source: MGI protein oligomerization Inferred from sequence orthology PubMed 18468998. Source: MGI regulation of catalytic activity Inferred from mutant phenotype PubMed 17276355. Source: MGI regulation of developmental growth Inferred from mutant phenotype PubMed 17317769. Source: MGI regulation of establishment of protein localization to plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB regulation of prostatic bud formation Inferred from genetic interaction PubMed 12941620. Source: MGI regulation of systemic arterial blood pressure Inferred from genetic interaction PubMed 18468998. Source: MGI response to insulin stimulus Inferred from electronic annotation. Source: Compara spermatogenesis Inferred from mutant phenotype PubMed 18403489. Source: MGI tertiary branching involved in mammary gland duct morphogenesis Inferred from mutant phenotype PubMed 14676301. Source: MGI
Cellular_component	axon Inferred from electronic annotation. Source: Compara cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB dendrite Inferred from electronic annotation. Source: Compara nuclear chromatin Inferred from sequence or structural similarity. Source: UniProtKB plasma membrane Inferred from direct assay PubMed 18468998. Source: MGI protein complex Inferred from sequence orthology PubMed 18468998. Source: MGI
Molecular_function	POU domain binding Inferred from direct assay PubMed 11997177. Source: UniProtKB androgen binding Inferred from electronic annotation. Source: Compara androgen receptor activity Inferred from sequence or structural similarity. Source: UniProtKB beta-catenin binding Inferred from sequence or structural similarity. Source: UniProtKB chromatin binding Inferred from electronic annotation. Source: Compara sequence-specific DNA binding Inferred from direct assay PubMed 8119157. Source: MGI transcription regulatory region DNA binding Inferred from sequence or structural similarity. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 899

899

Androgen receptor

PRO_0000053707

Regions

DNA binding

538 – 611

74

Nuclear receptor

Zinc finger

539 – 559

21

NR C4-type

Zinc finger

575 – 599

25

NR C4-type

Region

1 – 537

537

Modulating By similarity

Region

531 – 899

369

Interaction with LPXN By similarity

Region

551 – 641

91

Interaction with HIPK3 By similarity

Region

604 – 899

296

Interaction with KAT7 By similarity

Region

670 – 899

230

Ligand-binding

Compositional bias

63 – 67

5

Poly-Arg

Compositional bias

174 – 193

20

Poly-Gln

Compositional bias

367 – 373

7

Poly-Pro

Compositional bias

391 – 397

7

Poly-Ala

Compositional bias

441 – 447

7

Poly-Gly

Sites

Binding site

685

1

Androgen

Binding site

732

1

Androgen

Binding site

857

1

Androgen

Site

700

1

Interaction with coactivator LXXL motif By similarity

Site

877

1

Interaction with coactivator FXXLF motif By similarity

Amino acid modifications

Modified residue

61

1

Phosphoserine; by CDK9 By similarity

Modified residue

75

1

Phosphoserine By similarity

Modified residue

218

1

Phosphotyrosine; by CSK By similarity

Modified residue

262

1

Phosphotyrosine; by CSK and TNK2 By similarity

Modified residue

302

1

Phosphotyrosine; by CSK By similarity

Modified residue

341

1

Phosphotyrosine; by CSK By similarity

Modified residue

352

1

Phosphotyrosine; by CSK By similarity

Modified residue

357

1

Phosphotyrosine; by CSK By similarity

Modified residue

358

1

Phosphotyrosine; by CSK and TNK2 By similarity

Modified residue

388

1

Phosphotyrosine; by CSK By similarity

Modified residue

514

1

Phosphotyrosine; by CSK By similarity

Modified residue

531

1

Phosphotyrosine; by CSK By similarity

Modified residue

630

1

Phosphoserine; by STK4/MST1 By similarity

Modified residue

895

1

Phosphotyrosine; by CSK By similarity

Cross-link

381

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Cross-link

500

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Cross-link

825

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Cross-link

827

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Secondary structure

1

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899

Helix Strand Turn

Details...

Helix

652 – 659

8

Helix

677 – 701

25

Helix

705 – 707

3

Helix

710 – 736

27

Beta strand

740 – 745

6

Beta strand

748 – 750

3

Helix

752 – 757

6

Helix

761 – 776

16

Helix

781 – 792

12

Beta strand

794 – 799

6

Helix

804 – 823

20

Helix

831 – 844

14

Helix

846 – 862

17

Turn

863 – 868

6

Helix

873 – 887

15

Beta strand

890 – 893

4

Sequences

	Sequence		Length	Mass (Da)
	P19091 [UniParc]. Last modified November 1, 1990. Version 1. Checksum: FD9EE07C07F7A568	FASTA	899	98,194
	10 20 30 40 50 60 MEVQLGLGRV YPRPPSKTYR GAFQNLFQSV REAIQNPGPR HPEAANIAPP GACLQQRQET 70 80 90 100 110 120 SPRRRRRQQH TEDGSPQAHI RGPTGYLALE EEQQPSQQQA ASEGHPESSC LPEPGAATAP 130 140 150 160 170 180 GKGLPQQPPA PPDQDDSAAP STLSLLGPTF PGLSSCSADI KDILNEAGTM QLLQQQQQQQ 190 200 210 220 230 240 QHQQQHQQHQ QQQEVISEGS SARAREATGA PSSSKDSYLG GNSTISDSAK ELCKAVSVSM 250 260 270 280 290 300 GLGVEALEHL SPGEQLRGDC MYASLLGGPP AVRPTPCAPL PECKGLPLDE GPGKSTEETA 310 320 330 340 350 360 EYSSFKGGYA KGLEGESLGC SGSSEAGSSG TLEIPSSLSL YKSGALDEAA AYQNRDYYNF 370 380 390 400 410 420 PLALSGPPHP PPPTHPHARI KLENPLDYGS AWAAAAAQCR YGDLGSLHGG SVAGPSTGSP 430 440 450 460 470 480 PATTSSSWHT LFTAEEGQLY GPGGGGGSSS PSDAGPVAPY GYTRPPQGLT SQESDYSASE 490 500 510 520 530 540 VWYPGGVVNR VPYPSPNCVK SEMGPWMENY SGPYGDMRLD STRDHVLPID YYFPPQKTCL 550 560 570 580 590 600 ICGDEASGCH YGALTCGSCK VFFKRAAEGK QKYLCASRND CTIDKFRRKN CPSCRLRKCY 610 620 630 640 650 660 EAGMTLGARK LKKLGNLKLQ EEGENSNAGS PTEDPSQKMT VSHIEGYECQ PIFLNVLEAI 670 680 690 700 710 720 EPGVVCAGHD NNQPDSFAAL LSSLNELGER QLVHVVKWAK ALPGFRNLHV DDQMAVIQYS 730 740 750 760 770 780 WMGLMVFAMG WRSFTNVNSR MLYFAPDLVF NEYRMHKSRM YSQCVRMRHL SQEFGWLQIT 790 800 810 820 830 840 PQEFLCMKAL LLFSIIPVDG LKNQKFFDEL RMNYIKELDR IIACKRKNPT SCSRRFYQLT 850 860 870 880 890 KLLDSVQPIA RELHQFTFDL LIKSHMVSVD FPEMMAEIIS VQVPKILSGK VKPIYFHTQ

References

[1]	"Molecular cloning of androgen receptors from divergent species with a polymerase chain reaction technique: complete cDNA sequence of the mouse androgen receptor and isolation of androgen receptor cDNA probes from dog, guinea pig and clawed frog." He W.W., Fischer L.M., Sun S., Bilhartz D.L., Zhu X., Young C.Y.F., Kelley D.B., Tindall D.J. Biochem. Biophys. Res. Commun. 171:697-704(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: BALB/c.
[2]	"Structure and size distribution of the androgen receptor mRNA in wild-type and Tfm/Y mutant mice." Gaspar M.L., Meo T., Tosi M. Mol. Endocrinol. 4:1600-1610(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"The mouse androgen receptor. Functional analysis of the protein and characterization of the gene." Faber P.W., King A., van Rooij H.C.J., Brinkmann A.O., de Both N.J., Trapman J. Biochem. J. 278:269-278(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"A frameshift mutation destabilizes androgen receptor messenger RNA in the Tfm mouse." Charest N.J., Zhou Z., Lubahn D.B., Olsen K.L., Wilson E.M., French F.S. Mol. Endocrinol. 5:573-581(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]	"Novel ATPase of SNF2-like protein family interacts with androgen receptor and modulates androgen-dependent transcription." Rouleau N., Domans'kyi A., Reeben M., Moilanen A.-M., Havas K., Kang Z., Owen-Hughes T., Palvimo J.J., Jaenne O.A. Mol. Biol. Cell 13:2106-2119(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RAD54L2. Strain: Swiss Webster. Tissue: Embryo.
[6]	"Dyrk1A potentiates steroid hormone-induced transcription via the chromatin remodeling factor Arip4." Sitz J.H., Tigges M., Baumgaertel K., Khaspekov L.G., Lutz B. Mol. Cell. Biol. 24:5821-5834(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RAD54L2.
[7]	"A zinc finger protein TZF is a novel corepressor of androgen receptor." Ishizuka M., Kawate H., Takayanagi R., Ohshima H., Tao R.-H., Hagiwara H. Biochem. Biophys. Res. Commun. 331:1025-1031(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ZNF318.
[8]	"GAC63, a GRIP1-dependent nuclear receptor coactivator." Chen Y.-H., Kim J.H., Stallcup M.R. Mol. Cell. Biol. 25:5965-5972(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SLC30A9.
[9]	"A surface on the androgen receptor that allosterically regulates coactivator binding." Estebanez-Perpina E., Arnold L.A., Nguyen P., Rodrigues E.D., Mar E., Bateman R., Pallai P., Shokat K.M., Baxter J.D., Guy R.K., Webb P., Fletterick R.J. Proc. Natl. Acad. Sci. U.S.A. 104:16074-16079(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 649-899 IN COMPLEX WITH NCOA2 AND DIHYDROTESTOSTERONE.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

S56585 mRNA. Translation: AAB19916.1.
X53779 mRNA. Translation: CAA37795.1.
M37890 mRNA. Translation: AAA37234.1.
X59592 mRNA. Translation: CAA42160.1.

IPI

IPI00113217.

PIR

A35895.

RefSeq

NP_038504.1. NM_013476.3.

UniGene

Mm.39005.
Mm.394224.
Mm.439657.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2QPY	X-ray	2.50	A	649-899	[»]

ProteinModelPortal

P19091.

SMR

P19091. Positions 535-898.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-41803N.

IntAct

P19091. 1 interaction.

MINT

MINT-151935.

PTM databases

PhosphoSite

P19091.

Proteomic databases

PRIDE

P19091.

Protocols and materials databases

DNASU

11835.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000052837; ENSMUSP00000052648; ENSMUSG00000046532.

GeneID

11835.

KEGG

mmu:11835.

Organism-specific databases

CTD

367.

MGI

MGI:88064. Ar.

Phylogenomic databases

eggNOG

NOG245477.

GeneTree

ENSGT00700000104072.

HOGENOM

HOG000254783.

HOVERGEN

HBG007583.

InParanoid

P19091.

KO

K08557.

OrthoDB

EOG4XPQFV.

Gene expression databases

ArrayExpress

P19091.

Bgee

P19091.

CleanEx

MM_AR.

Genevestigator

P19091.

GermOnline

ENSMUSG00000046532. Mus musculus.

Family and domain databases

Gene3D

1.10.565.10. 2 hits.
3.30.50.10. 1 hit.

InterPro

IPR001103. Andrgn_rcpt.
IPR008946. Nucl_hormone_rcpt_ligand-bd.
IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]

Pfam

PF02166. Androgen_recep. 1 hit.
PF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]

PRINTS

PR00521. ANDROGENR.
PR00047. STROIDFINGER.

SMART

SM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]

SUPFAM

SSF48508. Str_ncl_receptor. 1 hit.

PROSITE

PS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P19091.

ChEMBL

CHEMBL3056.

EvolutionaryTrace

P19091.

NextBio

279763.

SOURCE

Search...

Entry information

Entry name

ANDR_MOUSE

Accession

Primary (citable) accession number: P19091

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1990
Last sequence update:	November 1, 1990
Last modified:	April 3, 2013
This is version 149 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program