Entry - *602145 - PROLIFERATION-ASSOCIATED 2G4, 38-KD; PA2G4 - OMIM
 
* 602145

PROLIFERATION-ASSOCIATED 2G4, 38-KD; PA2G4


Alternative titles; symbols

ERBB3-BINDING PROTEIN 1; EBP1


HGNC Approved Gene Symbol: PA2G4

Cytogenetic location: 12q13.2     Genomic coordinates (GRCh38): 12:56,104,559-56,113,910 (from NCBI)


TEXT

Cloning and Expression

The mouse Pa2g4 gene was isolated by Radomski and Jost (1995) by screening a cDNA expression library from a murine macrophage cell line with the antibody mAb2G4. This monoclonal antibody was generated against a single-stranded DNA-binding protein to identify proteins showing cell cycle specific variation in nuclear localization. The protein encoded by Pa2g4, p38-2G4, was shown to be confined to the nucleus during interphase and early prophase, but distributed throughout the cytoplasm from metaphase through to telophase. In addition, p38-2G4 was found to be highly expressed between G1 and mid-S phase, decreasing toward the end of S phase and ceasing at the S/G2 transition. As the protein is expressed in response to mitogen stimulation, it may belong to a large family of cell cycle regulatory proteins or replication proteins that maintain the cell cycle activities of proliferating cells. It appears to be a proliferation-dependent gene that probably encodes a nuclear DNA-binding protein involved in the control of cell replication.

Lamartine et al. (1997) isolated and characterized human PA2G4. A cDNA of 1,697 nucleotides was predicted to encode a protein of 394 amino acids. The deduced amino acid sequence of this human protein showed very strong homology to the mouse protein p38-2G4.

Liu et al. (2006) identified isoforms of Ebp1 with apparent molecular masses of 48 and 42 kD by SDS-PAGE in the rat PC12 pheochromocytoma cell line. The 48-kD isoform (p48) localized to both the cytoplasm and nucleus of PC12 cells, whereas the 42-kD isoform (p42) was predominantly localized in the cytoplasm.


Gene Function

Liu et al. (2006) found that the p48 isoform of Ebp1 suppressed apoptosis in rat PC12 cells, whereas the cytoplasmic p42 isoform promoted cell differentiation. EGF (131530) stimulated p42 to bind ERBB3 (190151) in transfected human embryonic kidney cells, and the association depended on PKC (see PRKCA; 176960)-mediated phosphorylation of p42. p48 did not bind ERBB3 regardless of EGF treatment. Overexpression of p48 induced PC12 cell proliferation, which was inhibited by p42. Nerve growth factor (NGFB; 162030) elicited extensive sprouting in p42-transfected PC12 cells, whereas p48 induced only modest neurite outgrowth. Akt (AKT1; 164730) was more active in p48 cells than in p42 cells. Liu et al. (2006) concluded that EBP1 may regulate cell survival and differentiation through 2 distinctive isoforms.


Mapping

Lamartine et al. (1997) concluded that PA2G4 belongs to a gene family with members in several chromosome regions: 3q24-q25, 6q22, 9q21, 12q13, 18q12, 20p12, and Xq25. They suggested that the human PA2G4 cDNA they analyzed probably corresponds to a functional copy at chromosome 12q13.


REFERENCES

  1. Lamartine, J., Seri, M., Cinti, R., Heitzmann, F., Creaven, M., Radomski, N., Jost, E., Lenoir, G. M., Romeo, G., Sylla, B. S. Molecular cloning and mapping of a human cDNA (PA2G4) that encodes a protein highly homologous to the mouse cell cycle protein p38-2G4. Cytogenet. Cell Genet. 78: 31-35, 1997. [PubMed: 9345902, related citations] [Full Text]

  2. Liu, Z., Ahn, J.-Y., Liu, X., Ye, K. Ebp1 isoforms distinctively regulate cell survival and differentiation. Proc. Nat. Acad. Sci. 103: 10917-10922, 2006. [PubMed: 16832058, images, related citations] [Full Text]

  3. Radomski, N., Jost, E. Molecular cloning of a murine cDNA encoding a novel protein, p38-2G4, which varies with the cell cycle. Exp. Cell Res. 220: 434-445, 1995. [PubMed: 7556453, related citations] [Full Text]


Contributors:
Patricia A. Hartz - updated : 10/3/2006
Creation Date:
Victor A. McKusick : 12/3/1997
mgross : 10/05/2006
terry : 10/3/2006
terry : 12/7/2001
dkim : 7/30/1998
dholmes : 1/23/1998
alopez : 12/15/1997
dholmes : 12/4/1997

* 602145

PROLIFERATION-ASSOCIATED 2G4, 38-KD; PA2G4


Alternative titles; symbols

ERBB3-BINDING PROTEIN 1; EBP1


HGNC Approved Gene Symbol: PA2G4

Cytogenetic location: 12q13.2     Genomic coordinates (GRCh38): 12:56,104,559-56,113,910 (from NCBI)


TEXT

Cloning and Expression

The mouse Pa2g4 gene was isolated by Radomski and Jost (1995) by screening a cDNA expression library from a murine macrophage cell line with the antibody mAb2G4. This monoclonal antibody was generated against a single-stranded DNA-binding protein to identify proteins showing cell cycle specific variation in nuclear localization. The protein encoded by Pa2g4, p38-2G4, was shown to be confined to the nucleus during interphase and early prophase, but distributed throughout the cytoplasm from metaphase through to telophase. In addition, p38-2G4 was found to be highly expressed between G1 and mid-S phase, decreasing toward the end of S phase and ceasing at the S/G2 transition. As the protein is expressed in response to mitogen stimulation, it may belong to a large family of cell cycle regulatory proteins or replication proteins that maintain the cell cycle activities of proliferating cells. It appears to be a proliferation-dependent gene that probably encodes a nuclear DNA-binding protein involved in the control of cell replication.

Lamartine et al. (1997) isolated and characterized human PA2G4. A cDNA of 1,697 nucleotides was predicted to encode a protein of 394 amino acids. The deduced amino acid sequence of this human protein showed very strong homology to the mouse protein p38-2G4.

Liu et al. (2006) identified isoforms of Ebp1 with apparent molecular masses of 48 and 42 kD by SDS-PAGE in the rat PC12 pheochromocytoma cell line. The 48-kD isoform (p48) localized to both the cytoplasm and nucleus of PC12 cells, whereas the 42-kD isoform (p42) was predominantly localized in the cytoplasm.


Gene Function

Liu et al. (2006) found that the p48 isoform of Ebp1 suppressed apoptosis in rat PC12 cells, whereas the cytoplasmic p42 isoform promoted cell differentiation. EGF (131530) stimulated p42 to bind ERBB3 (190151) in transfected human embryonic kidney cells, and the association depended on PKC (see PRKCA; 176960)-mediated phosphorylation of p42. p48 did not bind ERBB3 regardless of EGF treatment. Overexpression of p48 induced PC12 cell proliferation, which was inhibited by p42. Nerve growth factor (NGFB; 162030) elicited extensive sprouting in p42-transfected PC12 cells, whereas p48 induced only modest neurite outgrowth. Akt (AKT1; 164730) was more active in p48 cells than in p42 cells. Liu et al. (2006) concluded that EBP1 may regulate cell survival and differentiation through 2 distinctive isoforms.


Mapping

Lamartine et al. (1997) concluded that PA2G4 belongs to a gene family with members in several chromosome regions: 3q24-q25, 6q22, 9q21, 12q13, 18q12, 20p12, and Xq25. They suggested that the human PA2G4 cDNA they analyzed probably corresponds to a functional copy at chromosome 12q13.


REFERENCES

  1. Lamartine, J., Seri, M., Cinti, R., Heitzmann, F., Creaven, M., Radomski, N., Jost, E., Lenoir, G. M., Romeo, G., Sylla, B. S. Molecular cloning and mapping of a human cDNA (PA2G4) that encodes a protein highly homologous to the mouse cell cycle protein p38-2G4. Cytogenet. Cell Genet. 78: 31-35, 1997. [PubMed: 9345902] [Full Text: https://doi.org/10.1159/000134621]

  2. Liu, Z., Ahn, J.-Y., Liu, X., Ye, K. Ebp1 isoforms distinctively regulate cell survival and differentiation. Proc. Nat. Acad. Sci. 103: 10917-10922, 2006. [PubMed: 16832058] [Full Text: https://doi.org/10.1073/pnas.0602923103]

  3. Radomski, N., Jost, E. Molecular cloning of a murine cDNA encoding a novel protein, p38-2G4, which varies with the cell cycle. Exp. Cell Res. 220: 434-445, 1995. [PubMed: 7556453] [Full Text: https://doi.org/10.1006/excr.1995.1335]


Contributors:
Patricia A. Hartz - updated : 10/3/2006

Creation Date:
Victor A. McKusick : 12/3/1997

Edit History:
mgross : 10/05/2006
terry : 10/3/2006
terry : 12/7/2001
dkim : 7/30/1998
dholmes : 1/23/1998
alopez : 12/15/1997
dholmes : 12/4/1997