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Gene Review:

GPHA2 - glycoprotein hormone alpha 2

Homo sapiens

Synonyms: A2, GPA2, Glycoprotein hormone alpha-2, MGC126572, Thyrostimulin subunit alpha, ...

Nagasaki, H. et al., Sudo, S. et al., Nakada, H. et al., Park, J.I. et al., Rairdan, G.J. et al., et al.

Okada, Ellsworth, Durnam, Haugen, Holloway, Kelley, Lewis, Ren, Sheppard, Storey, Waggie, Wolf, Yao, Webster,

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High impact information on GPHA2

Domain-swap experiments with Rx and a homologous disease resistance gene, Gpa2, showed that PVX recognition localized to the C-terminal half of the LRR domain [1].
The Tn antigenicity, as assayed by the binding to a monoclonal anti-Tn antibody (MLS 128), was found exclusively in the glycopeptides including three (cluster I) or four (cluster II) consecutive residues of GalNAc-Ser/Thr, whereas the glycopeptide (GPA-2) containing two nonconsecutive GalNAc-Ser/Thr residues had practically no Tn antigenicity [2].
However, neither transgenic overexpression of GPHA2 nor deletion of GPHB5 produces an overt phenotype in mice [3].
To explore the function of thyrostimulin in the rat, we have cloned rat GPA2 and GPB5, reconstituted the heterodimers in vitro, and confirmed that rat thyrostimulin activates TSHR with an affinity similar to that of TSH [4].
Furthermore, the levels of GPB5 remain constant during the estrus cycle, while those of GPA2 vary [4].

Biological context of GPHA2

Indeed, searches of vertebrate genomes have led to the identification of two novel glycoprotein hormone subunits, glycoprotein alpha 2 (GPA2) and glycoprotein beta 5 (GPB5), as well as their homologs in invertebrates [5].

Anatomical context of GPHA2

A quantitative analysis showed that the co-localization of GPA2 and GPB5 is restricted in the rat to the eye and the testis [4].

Associations of GPHA2 with chemical compounds

These findings indicated that fly GPA2/GPB5 is a ligand for DLGR1, thus showing the ancient origin of this glycoprotein hormone-seven transmembrane receptor-G protein signaling system [6].
Based on comparative genomic searches, we isolated the fly orthologs for human GPA2 and GPB5, each consisting of 10 cysteine residues likely involved in cystine-knot formation [6].

Analytical, diagnostic and therapeutic context of GPHA2

RT-PCR analyses in Drosophila melanogaster demonstrated the expression of GPA2 and GPB5 at different developmental stages [6].
In situ hybridization of the pituitary showed that while GPA2 is expressed in the anterior lobe, GPB5 is not detected in any of the lobes [4].

References

Distinct domains in the ARC region of the potato resistance protein Rx mediate LRR binding and inhibition of activation. Rairdan, G.J., Moffett, P. Plant Cell (2006) [Pubmed]
Epitopic structure of Tn glycophorin A for an anti-Tn antibody (MLS 128). Nakada, H., Inoue, M., Numata, Y., Tanaka, N., Funakoshi, I., Fukui, S., Mellors, A., Yamashina, I. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
A glycoprotein hormone expressed in corticotrophs exhibits unique binding properties on thyroid-stimulating hormone receptor. Okada, S.L., Ellsworth, J.L., Durnam, D.M., Haugen, H.S., Holloway, J.L., Kelley, M.L., Lewis, K.E., Ren, H., Sheppard, P.O., Storey, H.M., Waggie, K.S., Wolf, A.C., Yao, L.Y., Webster, P.J. Mol. Endocrinol. (2006) [Pubmed]
Differential expression of the thyrostimulin subunits, glycoprotein alpha2 and beta5 in the rat pituitary. Nagasaki, H., Wang, Z., Jackson, V.R., Lin, S., Nothacker, H.P., Civelli, O. J. Mol. Endocrinol. (2006) [Pubmed]
Conservation of the heterodimeric glycoprotein hormone subunit family proteins and the LGR signaling system from nematodes to humans. Park, J.I., Semyonov, J., Chang, C.L., Hsu, S.Y. Endocrine (2005) [Pubmed]
Heterodimeric fly glycoprotein hormone-alpha2 (GPA2) and glycoprotein hormone-beta5 (GPB5) activate fly leucine-rich repeat-containing G protein-coupled receptor-1 (DLGR1) and stimulation of human thyrotropin receptors by chimeric fly GPA2 and human GPB5. Sudo, S., Kuwabara, Y., Park, J.I., Hsu, S.Y., Hsueh, A.J. Endocrinology (2005) [Pubmed]

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