Tag Content
SG ID
SG00000537 
UniProt Accession
Theoretical PI
8.89  
Molecular Weight
59216 Da  
Genbank Nucleotide ID
Genbank Protein ID
Gene Name
ESR2 
Gene Synonyms/Alias
ESTRB, NR3A2 
Protein Name
Estrogen receptor beta 
Protein Synonyms/Alias
ER-beta Nuclear receptor subfamily 3 group A member 2; 
Organism
Homo sapiens (Human) 
NCBI Taxonomy ID
9606 
Chromosome Location
chr:14;64550950-64804830;-1
View in Ensembl genome browser  
Function in Stage
Function in Cell Type
Description
These findings suggest a complex interrelation between estrogen signaling and c-fos transcriptional activity within the human testis, with the increase of ERbeta mRNA being putatively a compensatory mechanism for lower c-fos expression in infertile men with damaged spermatogenesis. 
The information of related literatures
1. E. L. Aschim, A. Giwercman, O. Stahl, J. Eberhard, M. Cwikiel, A. Nordenskjold, T. B. Haugen, T. Grotmol and Y. L. Giwercman (2005) The RsaI polymorphism in the estrogen receptor-beta gene is associated with male infertility. J Clin Endocrinol Metab 90(9): 5343-8. 

Abstract
CONTEXT PMID: [15998774] 

2. F. C. Araujo, C. A. Oliveira, A. B. Reis, H. L. Del Puerto, A. S. Martins and F. M. Reis (2009) Expression of the proto-oncogene c-fos and the immunolocalization of c-fos, phosphorylated c-fos and estrogen receptor beta in the human testis. Histol Histopathol 24(12): 1515-22. 

Abstract
Spermatogenesis is under the control of a complex endocrine and paracrine system, including estrogen receptor (ER) signaling. In many target cells, ER promotes the transcription of c-fos and other proto-oncogenes to regulate cell growth and differentiation. Thus, in this study we evaluated the expression of the proto-oncogene c-fos and the immunolocalization of c-fos, phosphorylated c-fos and ERbeta proteins in the human testis. Testis tissue samples were obtained from 12 men undergoing orchiectomy as adjuvant treatment for prostate cancer, and were stained by immunohistochemistry for c-fos, phosphorylated c-fos and ERbeta localization. Both forms of c-fos proteins were immunoreactive, mainly in germ cells (spermatogonia, spermatocytes and spermatids) and Sertoli cells, while ERbeta was primarily present in somatic cells (Leydig, Sertoli and myofibrillar cells). In addition, testicular biopsies obtained from infertile men with obstructive azoospermia/normal spermatogenesis (n=8) or non-obstructive azoospermia/severely impaired spermatogenesis (n=12) were evaluated for c-fos and ERbeta mRNA levels using real time polymerase chain reaction. The expression of c-fos mRNA was significantly lower (fold change = 0.08, p<0.05) whereas that of ERbeta mRNA was higher (fold change = 9.43, p<0.05) in the testis of men with non-obstructive azoospermia compared to those with obstructive azoospermia. These findings suggest a complex interrelation between estrogen signaling and c-fos transcriptional activity within the human testis, with the increase of ERbeta mRNA being putatively a compensatory mechanism for lower c-fos expression in infertile men with damaged spermatogenesis. PMID: [19795350] 

3. E. L. Aschim, T. Saether, R. Wiger, T. Grotmol and T. B. Haugen (2004) Differential distribution of splice variants of estrogen receptor beta in human testicular cells suggests specific functions in spermatogenesis. J Steroid Biochem Mol Biol 92(1-2): 97-106. 

Abstract
A growing number of estrogen receptor beta (ER beta) splice variants are reported. Several of these have been discovered in testis, but with few exceptions little is known about their cellular localization. The aim of this study was to identify and elucidate the mRNA expression pattern of the different ER beta splice variants in human testicular cells. Northern analysis was performed on whole testis and fractions enriched in germ cells from untreated men and from estrogen-treated men undergoing sex change surgery. Probes were constructed in order to systematically screen for and identify various ER beta splice variants. Several ER beta bands were observed in the human testis, in which splice variants constituted the major part of total ER beta transcripts. Interestingly, only two ER beta wild-type transcripts were detected. These seem to be virtually absent from the haploid germ cells and are probably mainly located in somatic cells and/or primary spermatocytes. Several novel ER beta deletion variants were found in high levels in the haploid germ cell fractions and were nearly absent in testicular cells from the estrogen-treated men. The cell-dependent distribution raises the question whether splice variants may have specific functions in spermatogenesis, and whether the differential splicing of ER beta is regulated in a cell-specific manner. PMID: [15544935] 

4. J. E. Cavaco, S. S. Laurentino, A. Barros, M. Sousa and S. Socorro (2009) Estrogen receptors alpha and beta in human testis. Syst Biol Reprod Med 55(4): 137-44. 

Abstract
Currently, clinical and experimental evidence point to an essential role of estrogens and estrogen receptors in male fertility. The expression of estrogen receptor alpha (ERalpha) and beta (ERbeta) in human testis has been described. However, some studies were unable to detect ERalpha, while others report the expression of both isoforms, with ERbeta presenting a wide distribution within somatic and germinal testicular cells. This has suggested that estrogens may exert their testicular effects exclusively through ERbeta. The present work aims to study the expression of ERalpha and ERbeta in testicular biopsies of men with conserved and disrupted spermatogenesis, in order to better clarify the positive cell populations. Human testicular tissue was obtained from 10 men undergoing testicular biopsy for infertility relief due to azoospermia PMID: [19886769] 

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Figures for illustrating the function of this protein/gene
Function
Nuclear hormone receptor. Binds estrogens with anaffinity similar to that of ESR1, and activates expression ofreporter genes containing estrogen response elements (ERE) in anestrogen-dependent manner. Isoform beta-cx lacks ligand bindingability and has no or only very low ere binding activity resultingin the loss of ligand-dependent transactivation ability. DNA-binding by ESR1 and ESR2 is rapidly lost at 37 degrees Celsius inthe absence of ligand while in the presence of 17 beta-estradioland 4-hydroxy-tamoxifen loss in DNA-binding at elevatedtemperature is more gradual. 
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Subcellular Location
Nucleus. 
Tissue Specificity
Isoform beta-1 is expressed in testis andovary, and at a lower level in heart, brain, placenta, liver,skeletal muscle, spleen, thymus, prostate, colon, bone marrow,mammary gland and uterus. Also found in uterine bone, breast, andovarian tumor cell lines, but not in colon and liver tumors.Isoform beta-2 is expressed in spleen, thymus, testis and ovaryand at a lower level in skeletal muscle, prostate, colon, smallintestine, leukocytes, bone marrow, mammary gland and uterus.Isoform beta-3 is found in testis. Isoform beta-4 is expressed intestis, and at a lower level in spleen, thymus, ovary, mammarygland and uterus. Isoform beta-5 is expressed in testis, placenta,skeletal muscle, spleen and leukocytes, and at a lower level inheart, lung, liver, kidney, pancreas, thymus, prostate, colon,small intestine, bone marrow, mammary gland and uterus. Notexpressed in brain. 
Gene Ontology
GO IDGO termEvidence
GO:0005576 C:extracellular region NAS:GOC.
GO:0005739 C:mitochondrion IDA:MGI.
GO:0005654 C:nucleoplasm TAS:Reactome.
GO:0001046 F:core promoter sequence-specific DNA binding IDA:UniProtKB.
GO:0030284 F:estrogen receptor activity TAS:UniProtKB.
GO:0034056 F:estrogen response element binding IDA:UniProtKB.
GO:0004879 F:ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity NAS:UniProtKB.
GO:0005496 F:steroid binding TAS:UniProtKB.
GO:0003713 F:transcription coactivator activity TAS:ProtInc.
GO:0008270 F:zinc ion binding IEA:InterPro.
GO:0007420 P:brain development IEA:Compara.
GO:0007267 P:cell-cell signaling TAS:ProtInc.
GO:0060743 P:epithelial cell maturation involved in prostate gland development IEA:Compara.
GO:1900116 P:extracellular negative regulation of signal transduction NAS:GOC.
GO:0030520 P:intracellular estrogen receptor signaling pathway TAS:UniProtKB.
GO:0060766 P:negative regulation of androgen receptor signaling pathway IEA:Compara.
GO:0030308 P:negative regulation of cell growth NAS:UniProtKB.
GO:0050680 P:negative regulation of epithelial cell proliferation IEA:Compara.
GO:0000122 P:negative regulation of transcription from RNA polymerase II promoter IDA:UniProtKB.
GO:0001764 P:neuron migration IEA:Compara.
GO:0001541 P:ovarian follicle development IEA:Compara.
GO:0043065 P:positive regulation of apoptotic process IEA:Compara.
GO:0051091 P:positive regulation of sequence-specific DNA binding transcription factor activity IDA:UniProtKB.
GO:0060740 P:prostate gland epithelium morphogenesis IEA:Compara.
GO:0006367 P:transcription initiation from RNA polymerase II promoter TAS:Reactome.
GO:0060065 P:uterus development IEA:Compara.
GO:0060068 P:vagina development IEA:Compara.
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Interpro
IPR021064;    Estrogen_rcpt_beta_N.
IPR008946;    Nucl_hormone_rcpt_ligand-bd.
IPR000536;    Nucl_hrmn_rcpt_lig-bd_core.
IPR024178;    Oestrogen_rcpt-rel.
IPR001723;    Str_hrmn_rcpt.
IPR001628;    Znf_hrmn_rcpt.
IPR013088;    Znf_NHR/GATA.
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Pfam
PF12497;    ERbeta_N;    1.
PF00104;    Hormone_recep;    1.
PF00105;    zf-C4;    1.
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SMART
SM00430;    HOLI;    1.
SM00399;    ZnF_C4;    1.
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PROSITE
PS00031;    NUCLEAR_REC_DBD_1;    1.
PS51030;    NUCLEAR_REC_DBD_2;    1.
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PRINTS
PR00398;    STRDHORMONER.;   
PR00047;    STROIDFINGER.;   
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Created Date
18-Oct-2012 
Record Type
Experiment identified 
Protein sequence Annotation
CHAIN         1    530       Estrogen receptor beta.
                             /FTId=PRO_0000053642.
DNA_BIND    149    214       Nuclear receptor.
ZN_FING     149    169       NR C4-type.
ZN_FING     185    209       NR C4-type.
REGION        1    148       Modulating.
REGION      215    530       Steroid-binding.
MOD_RES      87     87       Phosphoserine (By similarity).
MOD_RES     488    488       Phosphotyrosine (By similarity).
VAR_SEQ     319    409       Missing (in isoform 7).
                             /FTId=VSP_003685.
VAR_SEQ     319    323       FVELS -> MRGNA (in isoform 3).
                             /FTId=VSP_003684.
VAR_SEQ     324    530       Missing (in isoform 3).
                             /FTId=VSP_003686.
VAR_SEQ     365    375       DEGKCVEGILE -> YVPSGHSDPGC (in isoform
                             8).
                             /FTId=VSP_003687.
VAR_SEQ     376    530       Missing (in isoform 8).
                             /FTId=VSP_003688.
VAR_SEQ     469    530       SNKGMEHLLNMKCKNVVPVYDLLLEMLNAHVLRGCKSSITG
                             SECSPAEDSKSKEGSQNPQSQ -> RAEKASQTLTSFGMKM
                             ETLLPEATMEQ (in isoform 2).
                             /FTId=VSP_003689.
VAR_SEQ     469    530       SNKGMEHLLNMKCKNVVPVYDLLLEMLNAHVLRGCKSSITG
                             SECSPAEDSKSKEGSQNPQSQ -> SSLSLSWRLFMLREAS
                             CHGVRQTPGGAHMSVSRSRSFEACQQPRE (in isoform
                             4).
                             /FTId=VSP_003690.
VAR_SEQ     469    530       SNKGMEHLLNMKCKNVVPVYDLLLEMLNAHVLRGCKSSITG
                             SECSPAEDSKSKEGSQNPQSQ -> RWGEKQFIHLKLS
                             (in isoform 5).
                             /FTId=VSP_003691.
VAR_SEQ     469    530       SNKGMEHLLNMKCKNVVPVYDLLLEMLNAHVLRGCKSSITG
                             SECSPAEDSKSKEGSQNPQSQ -> RYAP (in isoform
                             6).
                             /FTId=VSP_003692.
HELIX       261    263
HELIX       265    275
STRAND      286    288
HELIX       291    314
HELIX       319    321
HELIX       324    347
STRAND      348    350
STRAND      353    357
STRAND      359    363
HELIX       364    369
HELIX       373    389
HELIX       394    406
STRAND      407    409
HELIX       411    413
HELIX       417    419
HELIX       421    442
TURN        443    445
HELIX       448    481
STRAND      482    484
HELIX       489    497
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Nucleotide Sequence
Length: 1740 bp   Go to nucleotide: FASTA
Protein Sequence
Length: 530 bp   Go to amino acid: FASTA
The verified Protein-Protein interaction information
UniProt
Gene Symbol Ref Databases
YWHAQBioGRID 
_BioGRID 
ADIPOR1String 
ADIPOR2String 
AKT1HPRD 
PRMT2IntAct 
AKT1HPRD 
BCAS2HPRD 
_HPRD 
_HPRD 
DAP3BioGRID 
_BioGRID 
DDX54HPRD 
DAP3BioGRID 
ESR1BioGRID 
YWHAHHPRD 
JMJD1CBioGRID 
_HPRD 
_HPRD 
ACAD11IntAct 
ACSM2BIntAct 
ACTBIntAct 
ACTN1IntAct 
ACTN3IntAct 
ADIPOR1String 
ADIPOR2String 
AKAP8IntAct 
AKAP9IntAct 
AKAP13HPRD 
ANKFY1IntAct 
PRMT2HPRD 
AP2A1IntAct 
ANAPC5IntAct 
ACTR3IntAct 
ARPC2IntAct 
ASB2IntAct 
ATG2AIntAct 
_HPRD 
_BioGRID 
CALM1HPRD 
_BioGRID 
_HPRD 
BAZ1AIntAct 
BCLAF1IntAct 
BAIAP2L1IntAct 
BICD1IntAct 
BRD8IntAct 
CALM1HPRD 
CREBBPBioGRID 
CCDC106IntAct 
CCAR1IntAct 
CCNCBioGRID 
CDC16IntAct 
CDC5LIntAct 
CDK8BioGRID 
C9orf114IntAct 
CGNIntAct 
C10orf47IntAct 
CLASP2IntAct 
CLCF1IntAct 
C14orf43IntAct 
CNN1IntAct 
CEP110IntAct 
COILIntAct 
COPB2IntAct 
COPG2IntAct 
CPSF6IntAct 
CPT1AIntAct 
C19orf68IntAct 
CTNNB1IntAct 
CWC15IntAct 
CWC27IntAct 
DDX17BioGRID 
DDX3XIntAct 
DDX41IntAct 
DDX50IntAct 
DDX5BioGRID 
DLGAP4IntAct 
DOK6IntAct 
DBN1IntAct 
DDX39AIntAct 
EPB41L5IntAct 
EDC4IntAct 
EEF1A2IntAct 
EIF2AIntAct 
MLLT1IntAct 
EPS15L1IntAct 
EP300BioGRID 
GSPT1IntAct 
ESR1HPRD 
ESR2HPRD 
ESR2HPRD 
EXOSC4IntAct 
EXOSC10IntAct 
FAM120AIntAct 
FAM179BIntAct 
NR0B1HPRD 
FBLL1IntAct 
FLGIntAct 
FIP1L1IntAct 
FLNBIntAct 
FLNCIntAct 
FMR1IntAct 
FXR2IntAct 
GNB3IntAct 
GNB2L1IntAct 
GCC2IntAct 
GSNIntAct 
GFAPIntAct 
GNL3IntAct 
GOLGA3IntAct 
GOLGA4IntAct 
HIST1H1CIntAct 
H2BFSIntAct 
HIST1H4AIntAct 
HRIntAct 
HCFC1IntAct 
HCFC2IntAct 
HEATR4IntAct 
HNRNPCL1IntAct 
RBMXL2IntAct 
HNRNPH2IntAct 
HP1BP3IntAct 
HSPA1AIntAct 
HSPA6IntAct 
HSPA8IntAct 
HTATSF1IntAct 
NFKBIBBioGRID 
JMJD1CBioGRID 
KANK2IntAct 
KATNAL2IntAct 
KHDRBS1IntAct 
MKI67IntAct 
KRI1IntAct 
LACTBIntAct 
LAD1IntAct 
LAMB1IntAct 
LARP1IntAct 
LAS1LIntAct 
LIMA1IntAct 
LONP1IntAct 
LRRC59IntAct 
LRRC1IntAct 
LYARIntAct 
MYBBP1AIntAct 
MAD2L1HPRD 
MED10BioGRID 
MED12BioGRID 
MED13IntAct 
MED14BioGRID 
MED16BioGRID 
MED17BioGRID 
MED1BioGRID 
MED20BioGRID 
MED21BioGRID 
MED23BioGRID 
MED24BioGRID 
MED27IntAct 
MED4IntAct 
MED6BioGRID 
MED7BioGRID 
MAPK11HPRD 
MKNK2BioGRID 
MSH2BioGRID 
MTA2IntAct 
MYH13IntAct 
MYH14IntAct 
MYH4IntAct 
MYH7BIntAct 
MYH7IntAct 
MYL6IntAct 
MYLK2IntAct 
MYO1CIntAct 
MYO1DIntAct 
MYO3BIntAct 
NAT10IntAct 
NBPF8IntAct 
NCBP1IntAct 
NCOA1BioGRID 
NCOA2BioGRID 
NCOA3BioGRID 
NCOA6BioGRID 
NCOA7HPRD 
NEBLIntAct 
NEFHIntAct 
NKRFIntAct 
GTPBP4IntAct 
GNL2IntAct 
NOLC1IntAct 
NOP56IntAct 
NR0B1HPRD 
NRIP1HPRD 
NUP205IntAct 
POM121IntAct 
POM121CIntAct 
PABPC3IntAct 
PABPC5IntAct 
SERBP1IntAct 
PABPC1LIntAct 
PBRM1IntAct 
POLDIP3String 
PELP1HPRD 
PRPHIntAct 
GIGYF1IntAct 
PES1IntAct 
PIK3R4IntAct 
PIAS1HPRD 
PIAS3HPRD 
PIPIntAct 
PKP3IntAct 
PNRC1HPRD 
PNRC2HPRD 
PREPLIntAct 
PPP5CIntAct 
PPRC1IntAct 
PRRC2CIntAct 
PRDX3IntAct 
PRDX4IntAct 
PPARGC1AHPRD 
PRKDCIntAct 
PRKRAIntAct 
PRPF31IntAct 
PSMD12IntAct 
PSMD1IntAct 
PTCD3IntAct 
PTPN23IntAct 
PURAIntAct 
PURBIntAct 
PWP1IntAct 
MED23BioGRID 
CREBBPBioGRID 
PPARGC1HPRD 
_BioGRID 
_BioGRID 
_HPRD 
CRSP9BioGRID 
ESR2HPRD 
CCNCBioGRID 
EP300BioGRID 
DKFZp761B2210HPRD 
_BioGRID 
_HPRD 
UBE3ABioGRID 
UBE3ABioGRID 
_HPRD 
_HPRD 
_BioGRID 
_BioGRID 
_IntAct 
CHMIntAct 
RALYIntAct 
RBM10IntAct 
RBM14IntAct 
RBM25IntAct 
RBM28IntAct 
RBM43IntAct 
RBM47IntAct 
TAF15IntAct 
RFC1IntAct 
RFC2IntAct 
RFC4IntAct 
RIMS2IntAct 
RPL10AIntAct 
RPL17IntAct 
RPL18AIntAct 
RPL23AIntAct 
RPL23IntAct 
RPL29IntAct 
RPL32IntAct 
RPL36ALIntAct 
RPL36IntAct 
RPL3LIntAct 
RPL7AIntAct 
RPL7IntAct 
RPLP0IntAct 
MRPL44IntAct 
MRPL45IntAct 
FAM82A2IntAct 
POLR1EIntAct 
RPF2IntAct 
RRBP1IntAct 
FTSJ3IntAct 
RRP12IntAct 
RRP1BIntAct 
RRP1IntAct 
RPS11IntAct 
RPS13IntAct 
RPS16IntAct 
RPS17IntAct 
RPS18IntAct 
RPS24IntAct 
RPS25IntAct 
RPS26IntAct 
RPS27AIntAct 
RPS27LIntAct 
RPS3IntAct 
RPS4XIntAct 
RPS4Y1IntAct 
RPS6IntAct 
RPS7IntAct 
RPS9IntAct 
MRPS2IntAct 
MRPS5IntAct 
MRPS9IntAct 
MRPS15IntAct 
MRPS21IntAct 
MRPS22IntAct 
MRPS27IntAct 
MRPS31IntAct 
C22orf28IntAct 
SCN1AIntAct 
SEMG2IntAct 
SENP3IntAct 
SERPINH1BioGRID 
SF3A1IntAct 
SF3B3IntAct 
SHROOM3IntAct 
SIPA1L2IntAct 
SIN3AIntAct 
SMAD3HPRD 
SMC1AIntAct 
SMARCA5IntAct 
SMN1IntAct 
SMARCC2IntAct 
SMTNIntAct 
SND1IntAct 
SP1HPRD 
SPRR1BIntAct 
SPTBN2IntAct 
CTTNIntAct 
SRCBioGRID 
SRRM2IntAct 
SRSF2IntAct 
SRSF5IntAct 
SSR1IntAct 
STAT5AHPRD 
STAU1IntAct 
STK31IntAct 
SURF6IntAct 
SYNGAP1IntAct 
TCOF1IntAct 
DNTTIP1IntAct 
TEX10IntAct 
GTF3C1IntAct 
GTF3C2IntAct 
GTF3C3IntAct 
GTF3C4IntAct 
GTF3C5IntAct 
THOC6IntAct 
TRIM24BioGRID 
TRIM59HPRD 
TRIP4BioGRID 
TTC21BIntAct 
EFTUD2IntAct 
UBCBioGRID 
UBE3ABioGRID 
UBN1IntAct 
UBR3IntAct 
VIMIntAct 
VMACIntAct 
VPS41IntAct 
WDR18IntAct 
WDR62IntAct 
WNK4IntAct 
CSE1LIntAct 
SLC7A6IntAct 
_IntAct 
ZNF512BIntAct 
ZBTB17HPRD 
ZC3HAV1IntAct 
ZC3H18IntAct 
ZFP91IntAct 
ZFRIntAct 
ZNF638IntAct 
ZNHIT3BioGRID 
NR0B2HPRD 
PSMC3IPHPRD 
LCKHPRD 
MAD2L1BioGRID 
MED1HPRD 
MAPK1BioGRID 
MKNK2HPRD 
MMS19HPRD 
MSH2BioGRID 
MYOD1BioGRID 
NCOA1HPRD 
NCOA3HPRD 
NCOA6HPRD 
NCOR1HPRD 
NCOR2HPRD 
OXTHPRD 
NR0B2HPRD 
POLDIP3String 
PELP1BioGRID 
PIAS1DIP 
PIAS2BioGRID 
PIAS3DIP 
PPP5CIntAct 
MAPK1BioGRID 
MAPK1BioGRID 
SMAD2HPRD 
_BioGRID 
_BioGRID 
ESR2HPRD 
_BioGRID 
RBM39HPRD 
REXO4HPRD 
RBFOX2HPRD 
DAP3BioGRID 
SMAD2HPRD 
SMAD4HPRD 
SMARCE1HPRD 
BCAS2HPRD 
SREBF1HPRD 
SRCHPRD 
STAT5ABioGRID 
DNTTIP2HPRD 
TRIM24HPRD 
WIPI1HPRD 
ZBTB17DIP 
Other Protein-Protein interaction resources
String database  
View Microarray data
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