Entry - *607420 - GABA-A RECEPTOR-ASSOCIATED PROTEIN-LIKE PROTEIN 1; GABARAPL1 - OMIM
 
* 607420

GABA-A RECEPTOR-ASSOCIATED PROTEIN-LIKE PROTEIN 1; GABARAPL1


Alternative titles; symbols

GABARAP-LIKE PROTEIN 1
GLANDULAR EPITHELIAL CELL PROTEIN 1; GEC1
APG8-LIKE; APG8L


HGNC Approved Gene Symbol: GABARAPL1

Cytogenetic location: 12p13.2   Genomic coordinates (GRCh38) : 12:10,212,877-10,223,128 (from NCBI)


TEXT

Cloning and Expression

Pellerin et al. (1993) cloned guinea pig Gabarapl1, which they called Gec1, through a differential screen of estrogen-regulated sequences expressed by endometrial glandular epithelial cells. Using the guinea pig sequence as probe, Vernier-Magnin et al. (2001) cloned human GABARAPL1, which they called GEC1, from a placenta cDNA library. The deduced 117-amino acid protein shares 100% amino acid identity with guinea pig Gabarapl1 and 87% identity with GABARAP (605125). Northern blot analysis revealed a 1.9-kb transcript in all tissues examined.

By Northern blot analysis, Xin et al. (2001) found a 2.3-kb GABARAPL1 transcript expressed in all tissues examined, with highest levels in brain, heart, peripheral blood leukocytes, liver, kidney, placenta, and skeletal muscle. Moderate expression was found in pancreas, prostate, testis, ovary, lung, spleen, and colon, and low expression was found in thymus and small intestine. In addition, a 4.2-kb transcript was found in low abundance in ovary, peripheral blood leukocytes, and liver, and a 1.7-kb transcript was found in placenta at low levels. Xin et al. (2001) noted that the amino acid sequence of the human and mouse proteins are identical. Northern blot analysis of mouse tissues revealed high levels of a 1.8-kb transcript in brain and kidney, and high levels of a 1.3-kb transcript in testis and heart.


Gene Function

Apg8 is a ubiquitin-like protein involved in autophagy in yeast. A cysteine protease, Apg4, cleaves Apg8 to create a C-terminal glycine required for ubiquitin-like modification reactions. There are at least 4 mammalian Apg8 homologs: GATE16 (GABARAPL2; 607452), GABARAP, MAP1LC3 (see 601242), and APG8L. Hemelaar et al. (2003) found that mouse Atg4b (611338) acted on the C termini of these 4 Atg8 homologs, and that the reaction required the active-site cysteine of Atg4b. Although the amino acid sequences of these Apg8 homologs differ from one another by as much as 71%, their affinities for Atg4b were roughly comparable in competition experiments.

Behrends et al. (2010) reported a proteomic analysis of the autophagy interaction network (AIN) in human cells under conditions of ongoing (basal) autophagy, revealing a network of 751 interactions among 409 candidate interacting proteins with extensive connectivity among subnetworks. Many new AIN components have roles in vesicle trafficking, protein or lipid phosphorylation, and protein ubiquitination, and affect autophagosome number or flux when depleted by RNA interference. The 6 human orthologs of yeast autophagy-8 (ATG8), MAP1LC3A (601242), MAP1LC3B (609604), MAP1LC3C (609605), GABARAP (605125), GABARAPL1, and GABARAPL2, interact with a cohort of 67 proteins, with extensive binding partner overlap between family members, and frequent involvement of a conserved surface on ATG8 proteins known to interact with LC3-interacting regions in partner proteins. Behrends et al. (2010) concluded that their studies provided a global view of the mammalian autophagy interaction landscape and a resource for mechanistic analysis of this critical protein homeostasis pathway.


Gene Structure

Xin et al. (2001) determined that the GABARAPL1 gene contains 4 exons.


Mapping

By genomic sequence analysis, Vernier-Magnin et al. (2001) mapped the GABARAPL1 gene to chromosome 12.

By radiation hybrid analysis, Xin et al. (2001) mapped the GABARAPL1 gene to chromosome 12p12.3.


REFERENCES

  1. Behrends, C., Sowa, M. E., Gygi, S. P., Harper, J. W. Network organization of the human autophagy system. Nature 466: 68-76, 2010. [PubMed: 20562859, images, related citations] [Full Text]

  2. Hemelaar, J., Lelyveld, V. S., Kessler, B. M., Ploegh, H. L. A single protease, Apg4B, is specific for the autophagy-related ubiquitin-like proteins GATE-16, MAP1-LC3, GABARAP, and Apg8L. J. Biol. Chem. 278: 51841-51850, 2003. [PubMed: 14530254, related citations] [Full Text]

  3. Pellerin, I., Vuillermoz, C., Jouvenot, M., Ordener, C., Royez, M., Adessi, G. L. Identification and characterization of an early estrogen-regulated RNA in cultured guinea-pig endometrial cells. Molec. Cell. Endocr. 90: R17-R21, 1993. [PubMed: 8495796, related citations] [Full Text]

  4. Vernier-Magnin, S., Muller, S., Sallot, M., Radom, J., Musard, J.-F., Adami, P., Dulieu, P., Remy-Martin, J.-P., Jouvenot, M., Fraichard, A. A novel early estrogen-regulated gene gec1 encodes a protein related to GABARAP. Biochem. Biophys. Res. Commun. 284: 118-125, 2001. [PubMed: 11374880, related citations] [Full Text]

  5. Xin, Y., Yu, L., Chen, Z., Zheng, L., Fu, Q., Jiang, J., Zhang, P., Gong, R., Zhao, S. Cloning, expression patterns, and chromosome localization of three human and two mouse homologues of GABA-A receptor-associated protein. Genomics 74: 408-413, 2001. [PubMed: 11414770, related citations] [Full Text]


Ada Hamosh - updated : 9/27/2010
Patricia A. Hartz - updated : 8/3/2007
Patricia A. Hartz - updated : 12/30/2002
Creation Date:
Patricia A. Hartz : 12/12/2002
alopez : 09/28/2010
terry : 9/27/2010
mgross : 8/16/2007
terry : 8/3/2007
cwells : 12/30/2002
mgross : 12/12/2002

* 607420

GABA-A RECEPTOR-ASSOCIATED PROTEIN-LIKE PROTEIN 1; GABARAPL1


Alternative titles; symbols

GABARAP-LIKE PROTEIN 1
GLANDULAR EPITHELIAL CELL PROTEIN 1; GEC1
APG8-LIKE; APG8L


HGNC Approved Gene Symbol: GABARAPL1

Cytogenetic location: 12p13.2   Genomic coordinates (GRCh38) : 12:10,212,877-10,223,128 (from NCBI)


TEXT

Cloning and Expression

Pellerin et al. (1993) cloned guinea pig Gabarapl1, which they called Gec1, through a differential screen of estrogen-regulated sequences expressed by endometrial glandular epithelial cells. Using the guinea pig sequence as probe, Vernier-Magnin et al. (2001) cloned human GABARAPL1, which they called GEC1, from a placenta cDNA library. The deduced 117-amino acid protein shares 100% amino acid identity with guinea pig Gabarapl1 and 87% identity with GABARAP (605125). Northern blot analysis revealed a 1.9-kb transcript in all tissues examined.

By Northern blot analysis, Xin et al. (2001) found a 2.3-kb GABARAPL1 transcript expressed in all tissues examined, with highest levels in brain, heart, peripheral blood leukocytes, liver, kidney, placenta, and skeletal muscle. Moderate expression was found in pancreas, prostate, testis, ovary, lung, spleen, and colon, and low expression was found in thymus and small intestine. In addition, a 4.2-kb transcript was found in low abundance in ovary, peripheral blood leukocytes, and liver, and a 1.7-kb transcript was found in placenta at low levels. Xin et al. (2001) noted that the amino acid sequence of the human and mouse proteins are identical. Northern blot analysis of mouse tissues revealed high levels of a 1.8-kb transcript in brain and kidney, and high levels of a 1.3-kb transcript in testis and heart.


Gene Function

Apg8 is a ubiquitin-like protein involved in autophagy in yeast. A cysteine protease, Apg4, cleaves Apg8 to create a C-terminal glycine required for ubiquitin-like modification reactions. There are at least 4 mammalian Apg8 homologs: GATE16 (GABARAPL2; 607452), GABARAP, MAP1LC3 (see 601242), and APG8L. Hemelaar et al. (2003) found that mouse Atg4b (611338) acted on the C termini of these 4 Atg8 homologs, and that the reaction required the active-site cysteine of Atg4b. Although the amino acid sequences of these Apg8 homologs differ from one another by as much as 71%, their affinities for Atg4b were roughly comparable in competition experiments.

Behrends et al. (2010) reported a proteomic analysis of the autophagy interaction network (AIN) in human cells under conditions of ongoing (basal) autophagy, revealing a network of 751 interactions among 409 candidate interacting proteins with extensive connectivity among subnetworks. Many new AIN components have roles in vesicle trafficking, protein or lipid phosphorylation, and protein ubiquitination, and affect autophagosome number or flux when depleted by RNA interference. The 6 human orthologs of yeast autophagy-8 (ATG8), MAP1LC3A (601242), MAP1LC3B (609604), MAP1LC3C (609605), GABARAP (605125), GABARAPL1, and GABARAPL2, interact with a cohort of 67 proteins, with extensive binding partner overlap between family members, and frequent involvement of a conserved surface on ATG8 proteins known to interact with LC3-interacting regions in partner proteins. Behrends et al. (2010) concluded that their studies provided a global view of the mammalian autophagy interaction landscape and a resource for mechanistic analysis of this critical protein homeostasis pathway.


Gene Structure

Xin et al. (2001) determined that the GABARAPL1 gene contains 4 exons.


Mapping

By genomic sequence analysis, Vernier-Magnin et al. (2001) mapped the GABARAPL1 gene to chromosome 12.

By radiation hybrid analysis, Xin et al. (2001) mapped the GABARAPL1 gene to chromosome 12p12.3.


REFERENCES

  1. Behrends, C., Sowa, M. E., Gygi, S. P., Harper, J. W. Network organization of the human autophagy system. Nature 466: 68-76, 2010. [PubMed: 20562859] [Full Text: https://doi.org/10.1038/nature09204]

  2. Hemelaar, J., Lelyveld, V. S., Kessler, B. M., Ploegh, H. L. A single protease, Apg4B, is specific for the autophagy-related ubiquitin-like proteins GATE-16, MAP1-LC3, GABARAP, and Apg8L. J. Biol. Chem. 278: 51841-51850, 2003. [PubMed: 14530254] [Full Text: https://doi.org/10.1074/jbc.M308762200]

  3. Pellerin, I., Vuillermoz, C., Jouvenot, M., Ordener, C., Royez, M., Adessi, G. L. Identification and characterization of an early estrogen-regulated RNA in cultured guinea-pig endometrial cells. Molec. Cell. Endocr. 90: R17-R21, 1993. [PubMed: 8495796] [Full Text: https://doi.org/10.1016/0303-7207(93)90161-c]

  4. Vernier-Magnin, S., Muller, S., Sallot, M., Radom, J., Musard, J.-F., Adami, P., Dulieu, P., Remy-Martin, J.-P., Jouvenot, M., Fraichard, A. A novel early estrogen-regulated gene gec1 encodes a protein related to GABARAP. Biochem. Biophys. Res. Commun. 284: 118-125, 2001. [PubMed: 11374880] [Full Text: https://doi.org/10.1006/bbrc.2001.4908]

  5. Xin, Y., Yu, L., Chen, Z., Zheng, L., Fu, Q., Jiang, J., Zhang, P., Gong, R., Zhao, S. Cloning, expression patterns, and chromosome localization of three human and two mouse homologues of GABA-A receptor-associated protein. Genomics 74: 408-413, 2001. [PubMed: 11414770] [Full Text: https://doi.org/10.1006/geno.2001.6555]


Contributors:
Ada Hamosh - updated : 9/27/2010
Patricia A. Hartz - updated : 8/3/2007
Patricia A. Hartz - updated : 12/30/2002

Creation Date:
Patricia A. Hartz : 12/12/2002

Edit History:
alopez : 09/28/2010
terry : 9/27/2010
mgross : 8/16/2007
terry : 8/3/2007
cwells : 12/30/2002
mgross : 12/12/2002