* 612031

INHIBIN, BETA E; INHBE


Other entities represented in this entry:

ACTIVIN BETA-E, INCLUDED

HGNC Approved Gene Symbol: INHBE

Cytogenetic location: 12q13.3     Genomic coordinates (GRCh38): 12:57,455,307-57,458,025 (from NCBI)


TEXT

Description

INHBE is a member of the activin beta family (see INHBA; 147290) that plays a role in pancreatic exocrine cell growth and proliferation (Hashimoto et al., 2006).


Cloning and Expression

By degenerative PCR of a human liver cDNA library, followed by 5-prime and 3-prime PCR, Hashimoto et al. (2002) cloned INHBE, which they called activin beta-E subunit. The deduced 350-amino acid protein contains an N-terminal hydrophobic signal peptide and a potential N-glycosylation site. The proposed cleavage site at amino acids 232 to 236 would yield a mature 114-amino acid protein. INHBE shares 97% and 96% similarity with the mouse and rat activin beta-E orthologs, respectively. The deduced mature human beta-E subunit shares amino acid identity of 44%, 48%, and 64% with activin beta-A (INHBA; 147290), activin beta-B (INHBB; 147390), and activin beta-C (INHBC; 601233), respectively. Northern blot analysis of human tissues detected a 2.7-kb transcript with strong expression in liver and weak expression in heart, testis, peripheral blood leukocyte, placenta, and skeletal muscle.


Gene Function

Hashimoto et al. (2002) suggested that INHBE forms a homodimer based on identification of a 33-kD band under nonreducing conditions and a lower size with reducing conditions. GST pull-down assays showed that INHBE binds follistatin (FST; 136470).

The accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) causes ER stress and induces the unfolded protein response (UPR), a coordinated series of cellular events that increases the capacity of the ER to process the unfolded proteins and reduce the protein loads. Using microarray analysis, Dombroski et al. (2010) found that VLDLR (192977) and INHBE were among hundreds of genes upregulated by ER stress in immortalized human B cell lines. Their expression was also induced by ER stress in primary human fibroblasts, and the expression of VLDLR was induced by ER stress in keratinocytes, which do not express INHBE. The expression of many genes showed individual variation; however, both INHBE and VLDLR were consistently upregulated by ER stress in all 60 immortalized B cell lines examined.


Animal Model

Hashimoto et al. (2006) showed that transgenic mice overexpressing human INHBE exhibited decreased pancreas size with hypoplasia of pancreatic exocrine cells, suggesting that INHBE plays a role in inhibiting growth and proliferation of pancreatic acinar cells.


REFERENCES

  1. Dombroski, B. A., Nayak, R. R., Ewens, K. G., Ankener, W., Cheung, V. G., Spielman, R. S. Gene expression and genetic variation in response to endoplasmic reticulum stress in human cells. Am. J. Hum. Genet. 86: 719-729, 2010. [PubMed: 20398888, images, related citations] [Full Text]

  2. Hashimoto, O., Tsuchida, K., Ushiro, Y., Hosoi, Y., Hoshi, N., Sugino, H., Hasegawa, Y. cDNA cloning and expression of human activin beta-E subunit. Molec. Cell. Endocr. 194: 117-122, 2002. [PubMed: 12242034, related citations] [Full Text]

  3. Hashimoto, O., Ushiro, Y., Sekiyama, K., Yamaguchi, O., Yoshioka, K., Mutoh, K.-I., Hasegawa, Y. Impaired growth of pancreatic exocrine cells in transgenic mice expressing human activin beta-E subunit. Biochem. Biophys. Res. Commun. 341: 416-424, 2006. [PubMed: 16426570, related citations] [Full Text]


Contributors:
Patricia A. Hartz - updated : 06/04/2010
Creation Date:
Dorothy S. Reilly : 5/9/2008
alopez : 06/04/2010
wwang : 5/12/2008
wwang : 5/12/2008
wwang : 5/9/2008

* 612031

INHIBIN, BETA E; INHBE


Other entities represented in this entry:

ACTIVIN BETA-E, INCLUDED

HGNC Approved Gene Symbol: INHBE

Cytogenetic location: 12q13.3     Genomic coordinates (GRCh38): 12:57,455,307-57,458,025 (from NCBI)


TEXT

Description

INHBE is a member of the activin beta family (see INHBA; 147290) that plays a role in pancreatic exocrine cell growth and proliferation (Hashimoto et al., 2006).


Cloning and Expression

By degenerative PCR of a human liver cDNA library, followed by 5-prime and 3-prime PCR, Hashimoto et al. (2002) cloned INHBE, which they called activin beta-E subunit. The deduced 350-amino acid protein contains an N-terminal hydrophobic signal peptide and a potential N-glycosylation site. The proposed cleavage site at amino acids 232 to 236 would yield a mature 114-amino acid protein. INHBE shares 97% and 96% similarity with the mouse and rat activin beta-E orthologs, respectively. The deduced mature human beta-E subunit shares amino acid identity of 44%, 48%, and 64% with activin beta-A (INHBA; 147290), activin beta-B (INHBB; 147390), and activin beta-C (INHBC; 601233), respectively. Northern blot analysis of human tissues detected a 2.7-kb transcript with strong expression in liver and weak expression in heart, testis, peripheral blood leukocyte, placenta, and skeletal muscle.


Gene Function

Hashimoto et al. (2002) suggested that INHBE forms a homodimer based on identification of a 33-kD band under nonreducing conditions and a lower size with reducing conditions. GST pull-down assays showed that INHBE binds follistatin (FST; 136470).

The accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) causes ER stress and induces the unfolded protein response (UPR), a coordinated series of cellular events that increases the capacity of the ER to process the unfolded proteins and reduce the protein loads. Using microarray analysis, Dombroski et al. (2010) found that VLDLR (192977) and INHBE were among hundreds of genes upregulated by ER stress in immortalized human B cell lines. Their expression was also induced by ER stress in primary human fibroblasts, and the expression of VLDLR was induced by ER stress in keratinocytes, which do not express INHBE. The expression of many genes showed individual variation; however, both INHBE and VLDLR were consistently upregulated by ER stress in all 60 immortalized B cell lines examined.


Animal Model

Hashimoto et al. (2006) showed that transgenic mice overexpressing human INHBE exhibited decreased pancreas size with hypoplasia of pancreatic exocrine cells, suggesting that INHBE plays a role in inhibiting growth and proliferation of pancreatic acinar cells.


REFERENCES

  1. Dombroski, B. A., Nayak, R. R., Ewens, K. G., Ankener, W., Cheung, V. G., Spielman, R. S. Gene expression and genetic variation in response to endoplasmic reticulum stress in human cells. Am. J. Hum. Genet. 86: 719-729, 2010. [PubMed: 20398888] [Full Text: https://doi.org/10.1016/j.ajhg.2010.03.017]

  2. Hashimoto, O., Tsuchida, K., Ushiro, Y., Hosoi, Y., Hoshi, N., Sugino, H., Hasegawa, Y. cDNA cloning and expression of human activin beta-E subunit. Molec. Cell. Endocr. 194: 117-122, 2002. [PubMed: 12242034] [Full Text: https://doi.org/10.1016/s0303-7207(02)00157-0]

  3. Hashimoto, O., Ushiro, Y., Sekiyama, K., Yamaguchi, O., Yoshioka, K., Mutoh, K.-I., Hasegawa, Y. Impaired growth of pancreatic exocrine cells in transgenic mice expressing human activin beta-E subunit. Biochem. Biophys. Res. Commun. 341: 416-424, 2006. [PubMed: 16426570] [Full Text: https://doi.org/10.1016/j.bbrc.2005.12.205]


Contributors:
Patricia A. Hartz - updated : 06/04/2010

Creation Date:
Dorothy S. Reilly : 5/9/2008

Edit History:
alopez : 06/04/2010
wwang : 5/12/2008
wwang : 5/12/2008
wwang : 5/9/2008