SG ID

SG00001973 

UniProt Accession

INHBA_RAT;P18331;  

Theoretical PI

7.07  

Molecular Weight

47406 Da  

Genbank Nucleotide ID

M37482;  

Genbank Protein ID

AAA41436.1; 

Gene Name

Inhba 

Gene Synonyms/Alias

 

Protein Name

Inhibin beta A chain 

Protein Synonyms/Alias

Activin beta-A chain;Flags: Precursor 

Rattus norvegicus (Rat) 

10116 

Temporarily unavailable 

The information of related literatures

1. J. J. Buzzard, K. L. Loveland, M. K. O'Bryan, A. E. O'Connor, M. Bakker, T. Hayashi, N. G. Wreford, J. R. Morrison and D. M. de Kretser (2004) Changes in circulating and testicular levels of inhibin A and B and activin A during postnatal development in the rat. Endocrinology 145(7): 3532-41. 

Abstract
This study describes the testicular levels of inhibin/activin subunits by Northern analysis and in situ hybridization and serum and testicular levels of inhibins A and B and activin A by enzyme linked immunosorbent assays (ELISA) during postnatal development in the rat. We show that serum inhibin A levels are less than 4 pg/ml throughout postnatal life. Serum inhibin B levels peak at 572 +/- 119 pg/ml (mean +/- se) at d 40 post partum (pp) before falling to 182 +/- 35 pg/ml in mature males. Serum activin A decreases from 294 +/- 29 pg/ml at d 6 to 132 +/- 27 pg/ml at maturity. Within the testis, inhibin A levels fall from 0.330 +/- 0.108 ng/g at d 15 to less than 0.004 ng/g at maturity. Inhibin B levels peak at 43.9 +/- 4.2 ng/g at d 6 before falling to 1.6 +/- 0.13 ng/g at maturity. Testicular activin A levels fall from 18.6 +/- 2.2 ng/g at d 6 to 0.094 +/- 0.013 ng/g at maturity. Northern profiles of testicular inhibin/activin subunits correlate with immunoreactive levels demonstrated by ELISA. In situ hybridization suggests that beta(A) and beta(B) subunit expression is largely restricted to the seminiferous tubule, particularly Sertoli cells, spermatogonia, and primary spermatocytes. These data support the view that inhibin B is the major inhibin in the male rat and that levels relate to Sertoli cell number and activity. Furthermore, the demonstration of high local concentrations of activin A during the period of Sertoli cell proliferation and the onset of spermatogenesis support its proposed role because a modulator of testicular development and function. PMID: [15070852] 

2. Y. Okuma, K. Saito, A. E. O'Connor, D. J. Phillips, D. M. de Kretser and M. P. Hedger (2005) Reciprocal regulation of activin A and inhibin B by interleukin-1 (IL-1) and follicle-stimulating hormone (FSH) in rat Sertoli cells in vitro. J Endocrinol 185(1): 99-110. 

Abstract
In several biological systems, the inhibin beta(A) homodimer activin A is stimulated by, and in turn, inhibits the action of interleukin (IL)-1 (both IL-1alpha and IL-1beta) and IL-6. The possibility that a similar regulatory relationship operates within the testis was investigated. Sertoli cells from immature (20-day-old) rats were cultured with human IL-1alpha or IL-1beta, human IL-6 and/or ovine FSH or dibutyryl cAMP. Activin A and the inhibin dimers, inhibin A and inhibin B, were measured by specific ELISA. Immunoreactive inhibin (ir-inhibin) was measured by RIA. Activin/inhibin subunit mRNA expression was measured by quantitative real-time PCR. Both IL-1 isoforms, but not IL-6, stimulated activin A secretion through increased synthesis of beta(A)-subunit mRNA. IL-1 also stimulated activin A secretion by testicular peritubular cells. In contrast to the effect on activin A, IL-1 suppressed inhibin beta(B)-subunit and, to a lesser extent, alpha-subunit mRNA expression, thereby reducing basal and FSH-stimulated inhibin B secretion by the Sertoli cells. Conversely, FSH inhibited basal activin A secretion and antagonised the stimulatory effects of IL-1. Dibutyryl cAMP partially inhibited the action of IL-1 on activin A secretion, but had no significant effect on basal activin A secretion. Secretion of inhibin A was low in all treatment groups. These data demonstrate that IL-1 and FSH/cAMP exert a reciprocal regulation of activin A and inhibin B synthesis and release by the Sertoli cell, and suggest a role for activin A as a potential feedback regulator of IL-1 and IL-6 activity in the testis during normal spermatogenesis and in inflammation. PMID: [15817831] 

3. M. Blauer, S. Husgafvel, H. Syvala, P. Tuohimaa and T. Ylikomi (1999) Identification of a nuclear localization signal in activin/inhibin betaA subunit; intranuclear betaA in rat spermatogenic cells. Biol Reprod 60(3): 588-93. 

Abstract
Activin is a dimeric glycoprotein hormone that was initially characterized by its ability to stimulate pituitary FSH secretion and was subsequently recognized as a growth factor with diverse biological functions in a large variety of tissues. In the testis, activin has been implicated in the auto/paracrine regulation of spermatogenesis through its cognate cell membrane receptors on Sertoli and germ cells. In this study we provide evidence for intranuclear activin/inhibin betaA subunit and show its distribution in the rat seminiferous epithelium. We have shown by transient expression in HeLa cells of beta-galactosidase fusion proteins that the betaA subunit precursor contains a functional nuclear localization signal within the lysine-rich sequence corresponding to amino acids 231-244. In all stages of the rat seminiferous epithelial cycle, an intense immunohistochemical staining of nuclear betaA was demonstrated in intermediate or type B spermatogonia or primary spermatocytes in their initial stages of the first meiotic prophase, as well as in pachytene spermatocytes and elongating spermatids primarily in stages IX-XII. In some pachytene spermatocytes, the pattern of betaA immunoreactivity was consistent with the characteristic distribution of pachytene chromosomes. In the nuclei of round spermatids, betaA immunoreactivity was less intense, and in late spermatids it was localized in the residual cytoplasm, suggesting disposal of betaA before spermatozoal maturation. Immunoblot analysis of a protein extract from isolated testicular nuclei revealed a nuclear betaA species with a molecular mass of approximately 24 kDa, which is more than 1.5 times that of the mature activin betaA subunit present in activin dimers. These results suggest that activin/inhibin betaA may elicit its biological functions through two parallel signal transduction pathways, one involving the dimeric molecule and cell surface receptors and the other an alternately processed betaA sequence acting directly within the nucleus. According to our immunohistochemical data, betaA may play a significant role in the regulation of nuclear functions during meiosis and spermiogenesis. PMID: [10026103] 

4. T. Meehan, S. Schlatt, M. K. O'Bryan, D. M. de Kretser and K. L. Loveland (2000) Regulation of germ cell and Sertoli cell development by activin, follistatin, and FSH. Dev Biol 220(2): 225-37. 

Abstract
We have demonstrated a role for activin A, follistatin, and FSH in male germ cell differentiation at the time when spermatogonial stem cells and committed spermatogonia first appear in the developing testis. Testis fragments from 3-day-old rats were cultured for 1 or 3 days with various combinations of these factors, incubated with bromodeoxyuridine (BrdU) to label proliferating cells, and then processed for stereological analysis and detection of BrdU incorporation. Gonocyte numbers were significantly elevated in cultures treated with activin, while the combination of FSH and the activin antagonist, follistatin, increased the proportion of spermatogonia in the germ cell population after 3 days. All fragment groups treated with FSH contained a significantly higher proportion of proliferating Sertoli cells, while activin and follistatin each reduced Sertoli cell division. In situ hybridization and immunohistochemistry on normal rat testes demonstrated that gonocytes, but not spermatogonia, contain the activin beta(A) subunit mRNA and protein. In contrast, gonocytes first expressed follistatin mRNA and protein at 3 days after birth, concordant with the transition of gonocytes to spermatogonia. Collectively, these data demonstrate that germ cells have the potential to regulate their own maturation through production of endogenous activin A and follistatin. Sertoli cells were observed to produce the activin/inhibin beta(A) subunit, the inhibin alpha subunit, and follistatin, demonstrating that these cells have the potential to regulate germ cell maturation as well as their own development. These findings indicate that local regulation of activin bioactivity may underpin the coordinated development of germ cells and somatic cells at the onset of spermatogenesis. PMID: [10753512] 

Figures for illustrating the function of this protein/gene

Function

Inhibins and activins inhibit and activate,respectively, the secretion of follitropin by the pituitary gland.Inhibins/activins are involved in regulating a number of diversefunctions such as hypothalamic and pituitary hormone secretion,gonadal hormone secretion, germ cell development and maturation,erythroid differentiation, insulin secretion, nerve cell survival,embryonic axial development or bone growth, depending on theirsubunit composition. Inhibins appear to oppose the functions ofactivins. 

Subcellular Location

Secreted (By similarity). 

Tissue Specificity

 

Gene Ontology

GO ID	GO term	Evidence
GO:0043509	C:activin A complex	ISS:UniProtKB.
GO:0043512	C:inhibin A complex	IDA:RGD.
GO:0007050	P:cell cycle arrest	ISS:UniProtKB.
GO:0071397	P:cellular response to cholesterol	IDA:UniProtKB.
GO:0071372	P:cellular response to follicle-stimulating hormone stimulus	IDA:UniProtKB.
GO:0061029	P:eyelid development in camera-type eye	ISS:UniProtKB.
GO:0000082	P:G1/S transition of mitotic cell cycle	ISS:UniProtKB.
GO:0040007	P:growth	IEA:InterPro.
GO:0001942	P:hair follicle development	ISS:UniProtKB.
GO:0042541	P:hemoglobin biosynthetic process	ISS:UniProtKB.
GO:0002244	P:hemopoietic progenitor cell differentiation	ISS:UniProtKB.
GO:0006917	P:induction of apoptosis	ISS:UniProtKB.
GO:0008584	P:male gonad development	ISS:UniProtKB.
GO:0048333	P:mesodermal cell differentiation	IEA:Compara.
GO:0030308	P:negative regulation of cell growth	ISS:UniProtKB.
GO:0008285	P:negative regulation of cell proliferation	ISS:UniProtKB.
GO:0042476	P:odontogenesis	ISS:UniProtKB.
GO:0001541	P:ovarian follicle development	ISS:UniProtKB.
GO:0060021	P:palate development	ISS:UniProtKB.
GO:0045648	P:positive regulation of erythrocyte differentiation	ISS:UniProtKB.
GO:0060279	P:positive regulation of ovulation	ISS:UniProtKB.
GO:0010862	P:positive regulation of pathway-restricted SMAD protein phosphorylation	IEA:Compara.
GO:0045944	P:positive regulation of transcription from RNA polymerase II promoter	ISS:UniProtKB.
GO:0042701	P:progesterone secretion	ISS:UniProtKB.
GO:0032925	P:regulation of activin receptor signaling pathway	ISS:UniProtKB.
GO:0046880	P:regulation of follicle-stimulating hormone secretion	ISS:UniProtKB.

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Interpro

IPR000491;    Inhibin_betaA.
IPR001839;    TGF-b_C.
IPR001111;    TGF-b_N.
IPR015615;    TGF-beta-rel.
IPR017948;    TGFb_CS.
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Pfam

PF00019;    TGF_beta;    1.
PF00688;    TGFb_propeptide;    1.
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SMART

SM00204;    TGFB;    1.
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PROSITE

PS00250;    TGF_BETA_1;    1.
PS51362;    TGF_BETA_2;    1.
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PRINTS

PR00670;    INHIBINBA.;   
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Created Date

18-Oct-2012 

Record Type

Experiment identified 

Protein sequence Annotation

Nucleotide Sequence

Length: 1543 bp   Go to nucleotide: FASTA

Protein Sequence

Length: 424 bp   Go to amino acid: FASTA

The verified Protein-Protein interaction information

UniProt

Gene Symbol

Ref Databases

Other Protein-Protein interaction resources

String database  

UniProt	Gene Symbol	Ref Databases
AVR2A_RAT	Acvr2a	String
BAMBI_RAT	Bambi	String
ESR1_RAT	Esr1	String
FSTL3_RAT	Fstl3	String
FST_RAT	Fst	String
GON1_RAT	Gnrh1	String
IGSF1_RAT	Igsf1	String
INHA_RAT	Inha	String
AVR2A_RAT	Acvr2a	String
BAMBI_RAT	Bambi	String
ESR1_RAT	Esr1	String
FSTL3_RAT	Fstl3	String
FST_RAT	Fst	String
GON1_RAT	Gnrh1	String
IGSF1_RAT	Igsf1	String
INHA_RAT	Inha	String
INHBB_RAT	Inhbb	String
INHBC_RAT	Inhbc	String
INHBE_RAT	Inhbe	String
MSMB_RAT	Msmb	String
NR5A2_RAT	Nr5a2	String
STF1_RAT	Nr5a1	String
TGBR3_RAT	Tgfbr3	String
TGFB1_RAT	Tgfb1	String
TGFB2_RAT	Tgfb2	String
TGFB3_RAT	Tgfb3	String
TMM18_RAT	Tmem18	String
VLDLR_RAT	Vldlr	String
INHBB_RAT	Inhbb	String
INHBC_RAT	Inhbc	String
INHBE_RAT	Inhbe	String
MSMB_RAT	Msmb	String
NR5A2_RAT	Nr5a2	String
STF1_RAT	Nr5a1	String
TGBR3_RAT	Tgfbr3	String
TGFB1_RAT	Tgfb1	String
TGFB2_RAT	Tgfb2	String
TGFB3_RAT	Tgfb3	String
TMM18_RAT	Tmem18	String
VLDLR_RAT	Vldlr	String

View Microarray data

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