Entry - *606981 - GUANINE NUCLEOTIDE-BINDING PROTEIN, GAMMA-2; GNG2 - OMIM
 
* 606981

GUANINE NUCLEOTIDE-BINDING PROTEIN, GAMMA-2; GNG2


Alternative titles; symbols

G PROTEIN GAMMA-2 SUBUNIT
GUANINE NUCLEOTIDE-BINDING PROTEIN G(I)/G(O)


HGNC Approved Gene Symbol: GNG2

Cytogenetic location: 14q22.1     Genomic coordinates (GRCh38): 14:51,826,174-51,969,795 (from NCBI)


TEXT

Description

Heterotrimeric G proteins play vital roles in cellular responses to external signals. The specificity of a G protein-receptor interaction is primarily mediated by the gamma subunit.


Cloning and Expression

Modarressi et al. (2000) identified GNG2 by differential display RT-PCR of normal testis RNA and RNA from the testis of infertile and azoospermic patients. The full-length cDNA, obtained by 5-prime RACE, encodes a deduced 71-amino acid protein that is 100% homologous with the bovine, mouse, and rat GNG2 proteins. RT-PCR revealed expression in adult testis, adrenals, brain, white blood cells, and lung, but no or undetectable expression in testis from infertile or azoospermic patients, or in adult liver, muscle, or prostate. PCR of fetal tissues revealed highest expression in sternum and brain, intermediate expression in limbs, stomach, intestine, and kidney, and lowest expression in testis, heart, spleen, and lung. High expression was also found in tumor tissues from thyroid and parotid glands, in a squamous cell carcinoma, and in a lymphoid cell line, with little detected in granulation tissue.

Yu et al. (2001) independently cloned human GNG2 from a 22-week fetal liver cDNA library.


Gene Function

Modarressi et al. (2000) determined that the GNG2 gene contains 3 exons.

Wolfe et al. (2003) demonstrated that inhibition of the alpha-1H (Ca(v)3.2) (CACNA1H; 607904), but not alpha-1G (Ca(v)3.1) (CACNA1G; 604065), low voltage-activated calcium channels is mediated selectively by G protein beta-2-gamma-2 subunits (GNB2, 139390, and GNG2) that bind to the intracellular loop connecting channel transmembrane domains II and III. This region of the alpha-1H channel is crucial for inhibition, because its replacement abrogates inhibition and its transfer to nonmodulated alpha-1G channels confers beta-2-gamma-2-dependent inhibition. Beta-gamma reduces channel activity independent of voltage, a mechanism distinct from the established beta-gamma-dependent inhibition of non-L-type high voltage-activated channels of the Ca(v)2 family. Wolfe et al. (2003) concluded that their studies identified the alpha-1H channel as a new effector for G protein beta-gamma subunits, and highlight the selective signaling roles available for particular beta-gamma combinations.


Mapping

By PCR amplification of a panel of human and rodent cell hybrids and by FISH, Modarressi et al. (2000) mapped the GNG2 gene to chromosome 14q21. The mouse Gng2 gene maps to chromosome 14 (Downes et al., 1999).


REFERENCES

  1. Downes, G. B., Gilbert, D. J., Copeland, N. G., Gautam, N., Jenkins, N. A. Chromosomal mapping of five mouse G protein gamma subunits. Genomics 57: 173-176, 1999. [PubMed: 10191100, related citations] [Full Text]

  2. Modarressi, M. H., Taylor, K. E., Wolfe, J. Cloning, characterization, and mapping of the gene encoding the human G protein gamma-2 subunit. Biochem. Biophys. Res. Commun. 272: 610-615, 2000. [PubMed: 10833460, related citations] [Full Text]

  3. Wolfe, J. T., Wang, H., Howard, J., Garrison, J. C., Barrett, P. Q. T-type calcium channel regulation by specific G-protein beta-gamma subunits. Nature 424: 209-213, 2003. [PubMed: 12853961, related citations] [Full Text]

  4. Yu, Y., Zhang, C., Zhou, G., Wu, S., Qu, X., Wei, H., Xing, G., Dong, C., Zhai, Y., Wan, J., Ouyang, S., Li, L., Zhang, S., Zhou, K., Zhang, Y., Wu, C., He, F. Gene expression profiling in human fetal liver and identification of tissue- and developmental-stage-specific genes through compiled expression profiles and efficient cloning of full-length cDNAs. Genome Res. 11: 1392-1403, 2001. [PubMed: 11483580, related citations] [Full Text]


Contributors:
Ada Hamosh - updated : 8/4/2003
Creation Date:
Patricia A. Hartz : 5/23/2002
wwang : 06/15/2009
cwells : 11/7/2003
alopez : 8/6/2003
terry : 8/4/2003
carol : 7/9/2002
carol : 5/23/2002

* 606981

GUANINE NUCLEOTIDE-BINDING PROTEIN, GAMMA-2; GNG2


Alternative titles; symbols

G PROTEIN GAMMA-2 SUBUNIT
GUANINE NUCLEOTIDE-BINDING PROTEIN G(I)/G(O)


HGNC Approved Gene Symbol: GNG2

Cytogenetic location: 14q22.1     Genomic coordinates (GRCh38): 14:51,826,174-51,969,795 (from NCBI)


TEXT

Description

Heterotrimeric G proteins play vital roles in cellular responses to external signals. The specificity of a G protein-receptor interaction is primarily mediated by the gamma subunit.


Cloning and Expression

Modarressi et al. (2000) identified GNG2 by differential display RT-PCR of normal testis RNA and RNA from the testis of infertile and azoospermic patients. The full-length cDNA, obtained by 5-prime RACE, encodes a deduced 71-amino acid protein that is 100% homologous with the bovine, mouse, and rat GNG2 proteins. RT-PCR revealed expression in adult testis, adrenals, brain, white blood cells, and lung, but no or undetectable expression in testis from infertile or azoospermic patients, or in adult liver, muscle, or prostate. PCR of fetal tissues revealed highest expression in sternum and brain, intermediate expression in limbs, stomach, intestine, and kidney, and lowest expression in testis, heart, spleen, and lung. High expression was also found in tumor tissues from thyroid and parotid glands, in a squamous cell carcinoma, and in a lymphoid cell line, with little detected in granulation tissue.

Yu et al. (2001) independently cloned human GNG2 from a 22-week fetal liver cDNA library.


Gene Function

Modarressi et al. (2000) determined that the GNG2 gene contains 3 exons.

Wolfe et al. (2003) demonstrated that inhibition of the alpha-1H (Ca(v)3.2) (CACNA1H; 607904), but not alpha-1G (Ca(v)3.1) (CACNA1G; 604065), low voltage-activated calcium channels is mediated selectively by G protein beta-2-gamma-2 subunits (GNB2, 139390, and GNG2) that bind to the intracellular loop connecting channel transmembrane domains II and III. This region of the alpha-1H channel is crucial for inhibition, because its replacement abrogates inhibition and its transfer to nonmodulated alpha-1G channels confers beta-2-gamma-2-dependent inhibition. Beta-gamma reduces channel activity independent of voltage, a mechanism distinct from the established beta-gamma-dependent inhibition of non-L-type high voltage-activated channels of the Ca(v)2 family. Wolfe et al. (2003) concluded that their studies identified the alpha-1H channel as a new effector for G protein beta-gamma subunits, and highlight the selective signaling roles available for particular beta-gamma combinations.


Mapping

By PCR amplification of a panel of human and rodent cell hybrids and by FISH, Modarressi et al. (2000) mapped the GNG2 gene to chromosome 14q21. The mouse Gng2 gene maps to chromosome 14 (Downes et al., 1999).


REFERENCES

  1. Downes, G. B., Gilbert, D. J., Copeland, N. G., Gautam, N., Jenkins, N. A. Chromosomal mapping of five mouse G protein gamma subunits. Genomics 57: 173-176, 1999. [PubMed: 10191100] [Full Text: https://doi.org/10.1006/geno.1999.5763]

  2. Modarressi, M. H., Taylor, K. E., Wolfe, J. Cloning, characterization, and mapping of the gene encoding the human G protein gamma-2 subunit. Biochem. Biophys. Res. Commun. 272: 610-615, 2000. [PubMed: 10833460] [Full Text: https://doi.org/10.1006/bbrc.2000.2832]

  3. Wolfe, J. T., Wang, H., Howard, J., Garrison, J. C., Barrett, P. Q. T-type calcium channel regulation by specific G-protein beta-gamma subunits. Nature 424: 209-213, 2003. [PubMed: 12853961] [Full Text: https://doi.org/10.1038/nature01772]

  4. Yu, Y., Zhang, C., Zhou, G., Wu, S., Qu, X., Wei, H., Xing, G., Dong, C., Zhai, Y., Wan, J., Ouyang, S., Li, L., Zhang, S., Zhou, K., Zhang, Y., Wu, C., He, F. Gene expression profiling in human fetal liver and identification of tissue- and developmental-stage-specific genes through compiled expression profiles and efficient cloning of full-length cDNAs. Genome Res. 11: 1392-1403, 2001. [PubMed: 11483580] [Full Text: https://doi.org/10.1101/gr.175501]


Contributors:
Ada Hamosh - updated : 8/4/2003

Creation Date:
Patricia A. Hartz : 5/23/2002

Edit History:
wwang : 06/15/2009
cwells : 11/7/2003
alopez : 8/6/2003
terry : 8/4/2003
carol : 7/9/2002
carol : 5/23/2002