Entry - *611470 - GLUTAMATE-AMMONIA LIGASE (GLUTAMINE SYNTHETASE) DOMAIN-CONTAINING 1; GLULD1 - OMIM

 
 
* 611470

GLUTAMATE-AMMONIA LIGASE (GLUTAMINE SYNTHETASE) DOMAIN-CONTAINING 1; GLULD1


Alternative titles; symbols

LENGSIN; LGS


HGNC Approved Gene Symbol: LGSN

Cytogenetic location: 6q12     Genomic coordinates (GRCh38): 6:63,275,951-63,573,607 (from NCBI)


TEXT

▼ Cloning and Expression

By high-throughput sequencing of an adult human lens cDNA library, Wistow et al. (2002) cloned GLULD1, which they called lengsin. The deduced 509-amino acid protein most closely resembles glutamine synthetase type I (GLUL; 138290). GLULD1 was among the most abundant cDNAs identified in adult lens, and EST database analysis showed that GLULD1 is among the most abundant noncrystallin mRNAs in human lens.

By RT-PCR analysis of total RNA from human transparent lenses, Grassi et al. (2006) identified 3 GLULD1 splice variants. Database analysis showed that GLULD1 homologs were restricted to vertebrate eye-bearing organisms. All orthologs contain a putative 14-3-3 protein (see 113508)-binding site, which is absent in GLUL. GLULD1 transcripts were identified in human lens, total eye, and whole embryo ESTs, indicating preferential expression in the lens. Western blot analysis detected a 57-kD band in extracts from transparent but not cataractous lens. Downregulation of GLULD1 in cataractous lens was previously reported by Hawse et al. (2003).


▼ Gene Function

Grassi et al. (2006) detected no glutamine synthetase activity for lengsin, suggesting that it is not involved in removal of glutamate from the eye. By gradient gel electrophoresis and atomic force microscopy, they determined that lengsin is a dodecamer with an organization reminiscent of the double-ring structure of some multisubunit chaperones. Hydrophobic surface probe bis-ANS bound to 6 sites on lengsin, supporting a possible role as a chaperone; however, no anti-aggregating effect of lengsin was found. Beta-amyloid (104760) toxicity was relieved in a protein-folding-impaired yeast mutant by cotransformation with a GLULD1-bearing expression vector.


▼ Gene Structure

Grassi et al. (2006) determined that the GLULD1 gene contains a minimum of 5 core exons with 3 alternatively spliced exons.


▼ Mapping

By radiation hybrid analysis, Wistow et al. (2002) mapped the GLULD1 gene to chromosome 6q11.2.


▼ REFERENCES

  1. Grassi, F., Moretto, N., Rivetti, C., Cellai, S., Betti, M., Marquez, A. J., Maraini, G., Ottonello, S. Structural and functional properties of lengsin, a pseudo-glutamine synthetase in the transparent human lens. Biochem. Biophys. Res. Commun. 350: 424-429, 2006. [PubMed: 17010935, related citations] [Full Text]

  2. Hawse, J. R., Hejtmancik, J. F., Huang, Q., Sheets, N. L., Hosack, D. A., Lempicki, R. A., Horwitz, J., Kantorow, M. Identification and functional clustering of global gene expression differences between human age-related cataract and clear lenses. Molec. Vision 9: 515-537, 2003. [PubMed: 14551530, images, related citations]

  3. Wistow, G., Bernstein, S. L., Wyatt, M. K., Behal, A., Touchman, J. W., Bouffard, G., Smith, D., Peterson, K. Expressed sequence tag analysis of adult human lens for the NEIBank Project: over 2000 non-redundant transcripts, novel genes and splice variants. Molec. Vision 8: 171-184, 2002. [PubMed: 12107413, related citations]


Creation Date:
Jennifer L. Goldstein : 9/27/2007
Edit History:
wwang : 09/27/2007

* 611470

GLUTAMATE-AMMONIA LIGASE (GLUTAMINE SYNTHETASE) DOMAIN-CONTAINING 1; GLULD1


Alternative titles; symbols

LENGSIN; LGS


HGNC Approved Gene Symbol: LGSN

Cytogenetic location: 6q12     Genomic coordinates (GRCh38): 6:63,275,951-63,573,607 (from NCBI)


TEXT

Cloning and Expression

By high-throughput sequencing of an adult human lens cDNA library, Wistow et al. (2002) cloned GLULD1, which they called lengsin. The deduced 509-amino acid protein most closely resembles glutamine synthetase type I (GLUL; 138290). GLULD1 was among the most abundant cDNAs identified in adult lens, and EST database analysis showed that GLULD1 is among the most abundant noncrystallin mRNAs in human lens.

By RT-PCR analysis of total RNA from human transparent lenses, Grassi et al. (2006) identified 3 GLULD1 splice variants. Database analysis showed that GLULD1 homologs were restricted to vertebrate eye-bearing organisms. All orthologs contain a putative 14-3-3 protein (see 113508)-binding site, which is absent in GLUL. GLULD1 transcripts were identified in human lens, total eye, and whole embryo ESTs, indicating preferential expression in the lens. Western blot analysis detected a 57-kD band in extracts from transparent but not cataractous lens. Downregulation of GLULD1 in cataractous lens was previously reported by Hawse et al. (2003).


Gene Function

Grassi et al. (2006) detected no glutamine synthetase activity for lengsin, suggesting that it is not involved in removal of glutamate from the eye. By gradient gel electrophoresis and atomic force microscopy, they determined that lengsin is a dodecamer with an organization reminiscent of the double-ring structure of some multisubunit chaperones. Hydrophobic surface probe bis-ANS bound to 6 sites on lengsin, supporting a possible role as a chaperone; however, no anti-aggregating effect of lengsin was found. Beta-amyloid (104760) toxicity was relieved in a protein-folding-impaired yeast mutant by cotransformation with a GLULD1-bearing expression vector.


Gene Structure

Grassi et al. (2006) determined that the GLULD1 gene contains a minimum of 5 core exons with 3 alternatively spliced exons.


Mapping

By radiation hybrid analysis, Wistow et al. (2002) mapped the GLULD1 gene to chromosome 6q11.2.


REFERENCES

  1. Grassi, F., Moretto, N., Rivetti, C., Cellai, S., Betti, M., Marquez, A. J., Maraini, G., Ottonello, S. Structural and functional properties of lengsin, a pseudo-glutamine synthetase in the transparent human lens. Biochem. Biophys. Res. Commun. 350: 424-429, 2006. [PubMed: 17010935] [Full Text: https://doi.org/10.1016/j.bbrc.2006.09.062]

  2. Hawse, J. R., Hejtmancik, J. F., Huang, Q., Sheets, N. L., Hosack, D. A., Lempicki, R. A., Horwitz, J., Kantorow, M. Identification and functional clustering of global gene expression differences between human age-related cataract and clear lenses. Molec. Vision 9: 515-537, 2003. [PubMed: 14551530]

  3. Wistow, G., Bernstein, S. L., Wyatt, M. K., Behal, A., Touchman, J. W., Bouffard, G., Smith, D., Peterson, K. Expressed sequence tag analysis of adult human lens for the NEIBank Project: over 2000 non-redundant transcripts, novel genes and splice variants. Molec. Vision 8: 171-184, 2002. [PubMed: 12107413]


Creation Date:
Jennifer L. Goldstein : 9/27/2007

Edit History:
wwang : 09/27/2007



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OMIM® and Online Mendelian Inheritance in Man® are registered trademarks of the Johns Hopkins University.
Copyright® 1966-2024 Johns Hopkins University.

NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers, and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
OMIM® and Online Mendelian Inheritance in Man® are registered trademarks of the Johns Hopkins University.
Copyright® 1966-2024 Johns Hopkins University.
Printed: June 9, 2024