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* 607558

SEC14-LIKE LIPID-BINDING PROTEIN 2; SEC14L2


Alternative titles; symbols

SEC14-LIKE 2
SEC14, S. CEREVISIAE, HOMOLOG OF, 2
TOCOPHEROL-ASSOCIATED PROTEIN 1; TAP1
TAP
KIAA1186


HGNC Approved Gene Symbol:SEC14L2

Cytogenetic location:22q12.2   Genomic coordinates(GRCh38) :22:30,397,018-30,425,303 (from NCBI)


TEXT

Cloning and Expression

By sequencing clones obtained from a size-fractionated human brain cDNA library,Hirosawa et al. (1999) cloned a partial cDNA encoding SEC14L2, which they designated KIAA1186. RT-PCR followed by ELISA detected moderate expression in kidney, spleen, testis, ovary, and fetal liver. Lower levels were detected in whole brain, lung, and adult liver.

Zimmer et al. (2000) sequenced peptide fragments from bovine SEC14L2, which they called TAP, and searched a database using these sequences to identify human TAP. Using RT-PCR they cloned full-length TAP from human small intestine total RNA. The deduced 403-amino acid protein has a calculated molecular mass of about 46 kD and contains a conserved hydrophobic lipid-binding pocket called the CRAL (cis-retinal binding)/TRIO (triple function) domain. Human and bovine TAP share about 84% amino acid identity. mRNA dot blot analysis detected broad tissue distribution, with highest expression in liver, prostate, and brain. Northern blot analysis detected a major transcript of 2.8 kb and 2 minor transcripts of approximately 4.2 and 2.8 kb expressed at highest levels in liver and brain and more weakly in kidney.

By immunocytochemical studies,Kempna et al. (2003) showed that SEC14L2 localized to intracellular membranes of the cytoplasm in HeLa cells, including partial localization to the ER and Golgi, with more intense staining surrounding but not within the nucleus.


Gene Function

Using a biotinylated alpha-tocopherol derivative,Zimmer et al. (2000) demonstrated that recombinant TAP binds alpha-tocopherol at physiologic concentrations. Binding was dose-dependent and saturable.

By ligand competition analysis,Yamauchi et al. (2001) confirmed specific interaction between recombinant TAP and alpha-tocopherol. TAP did not significantly interact with any other tocopherols or tocotrienols examined. Alpha-tocopherol induced the translocation of TAP from the cytosol to the nucleus of transfected COS-7 cells. Transient transfection experiments showed that TAP activated transcription of a reporter gene in an alpha-tocopherol-dependent manner.Yamauchi et al. (2001) hypothesized that alpha-tocopherol is not only an antioxidant, but also a transcriptional regulator via its association with TAP.

Kempna et al. (2003) showed that in HeLa cells deletion of the C-terminal Golgi dynamics (GOLD) domain reduced SEC14L2 localization in the region surrounding the nucleus with some tubular sacs emerging. They suggested that the SEC14L2 GOLD domain may play a role in docking to other proteins or in intracellular transport of bound ligands. Using several assays,Kempna et al. (2003) demonstrated that SEC14L2 bound tocopherol, squalene, and phospholipids (phosphatidylcholine, phosphatidylinositol, phosphatidylglycerol). Although SEC14L2 bound phospholipids, it failed to complement an S. cerevisiae temperature-sensitive Sec14 allele in yeast. Using immunoprecipitation assays,Kempna et al. (2003) showed that SEC14L2 may interact with and regulate phosphatidylinositol 3-kinase activity, and SEC14L2 displayed low basal GTPase activity.

Saeed et al. (2015) found that SEC14L2 is necessary for hepatitis C virus replication in culture. Mechanistic studies suggested that SEC14L2 promotes HCV infection by enhancing vitamin E-mediated protection against lipid peroxidation.


Gene Structure

Zimmer et al. (2000) determined that the SEC14L2 gene contains 12 exons.


Mapping

By radiation hybrid analysis,Hirosawa et al. (1999) mapped the SEC14L2 gene to chromosome 22. By genomic sequence analysis,Zimmer et al. (2000) mapped the SEC14L2 gene to chromosome 22q12.1-qter.


REFERENCES

  1. Hirosawa, M., Nagase, T., Ishikawa, K., Kikuno, R., Nomura, N., Ohara, O.Characterization of cDNA clones selected by the GeneMark analysis from size-fractionated cDNA libraries from human brain. DNA Res. 6: 329-336, 1999. [PubMed:10574461,related citations] [Full Text]

  2. Kempna, P., Zingg, J.-M., Ricciarelli, R., Hierl, M., Saxena, S., Azzi, A.Cloning of novel human Sec14p-like proteins: ligand binding and functional properties. Free Radic. Biol. Med. 34: 1458-1472, 2003. [PubMed:12757856,related citations] [Full Text]

  3. Saeed, M., Andreo, U., Chung, H.-Y., Espiritu, C., Branch, A. D., Silva, J. M., Rice, C. M.SEC14L2 enables pan-genotype HCV replication in cell culture. Nature 524: 471-475, 2015. [PubMed:26266980,images,related citations] [Full Text]

  4. Yamauchi, J., Iwamoto, T., Kida, S., Masushige, S., Yamada, K., Esashi, T.Tocopherol-associated protein is a ligand-dependent transcriptional activator. Biochem. Biophys. Res. Commun. 285: 295-299, 2001. [PubMed:11444841,related citations] [Full Text]

  5. Zimmer, S., Stocker, A., Sarbolouki, M. N., Spycher, S. E., Sassoon, J., Azzi, A.A novel human tocopherol-associated protein: cloning, in vitro expression, and characterization. J. Biol. Chem. 275: 25672-25680, 2000. [PubMed:10829015,related citations] [Full Text]


Ada Hamosh - updated : 12/02/2015
Dorothy S. Reilly - updated : 5/28/2009
Creation Date:
Patricia A. Hartz : 2/11/2003
mgross : 06/29/2021
carol : 06/21/2019
alopez : 12/02/2015
wwang : 5/28/2009
terry : 7/20/2004
mgross : 2/11/2003

* 607558

SEC14-LIKE LIPID-BINDING PROTEIN 2; SEC14L2


Alternative titles; symbols

SEC14-LIKE 2
SEC14, S. CEREVISIAE, HOMOLOG OF, 2
TOCOPHEROL-ASSOCIATED PROTEIN 1; TAP1
TAP
KIAA1186


HGNC Approved Gene Symbol: SEC14L2

Cytogenetic location: 22q12.2   Genomic coordinates(GRCh38) : 22:30,397,018-30,425,303(from NCBI)


TEXT

Cloning and Expression

By sequencing clones obtained from a size-fractionated human brain cDNA library, Hirosawa et al. (1999) cloned a partial cDNA encoding SEC14L2, which they designated KIAA1186. RT-PCR followed by ELISA detected moderate expression in kidney, spleen, testis, ovary, and fetal liver. Lower levels were detected in whole brain, lung, and adult liver.

Zimmer et al. (2000) sequenced peptide fragments from bovine SEC14L2, which they called TAP, and searched a database using these sequences to identify human TAP. Using RT-PCR they cloned full-length TAP from human small intestine total RNA. The deduced 403-amino acid protein has a calculated molecular mass of about 46 kD and contains a conserved hydrophobic lipid-binding pocket called the CRAL (cis-retinal binding)/TRIO (triple function) domain. Human and bovine TAP share about 84% amino acid identity. mRNA dot blot analysis detected broad tissue distribution, with highest expression in liver, prostate, and brain. Northern blot analysis detected a major transcript of 2.8 kb and 2 minor transcripts of approximately 4.2 and 2.8 kb expressed at highest levels in liver and brain and more weakly in kidney.

By immunocytochemical studies, Kempna et al. (2003) showed that SEC14L2 localized to intracellular membranes of the cytoplasm in HeLa cells, including partial localization to the ER and Golgi, with more intense staining surrounding but not within the nucleus.


Gene Function

Using a biotinylated alpha-tocopherol derivative, Zimmer et al. (2000) demonstrated that recombinant TAP binds alpha-tocopherol at physiologic concentrations. Binding was dose-dependent and saturable.

By ligand competition analysis, Yamauchi et al. (2001) confirmed specific interaction between recombinant TAP and alpha-tocopherol. TAP did not significantly interact with any other tocopherols or tocotrienols examined. Alpha-tocopherol induced the translocation of TAP from the cytosol to the nucleus of transfected COS-7 cells. Transient transfection experiments showed that TAP activated transcription of a reporter gene in an alpha-tocopherol-dependent manner. Yamauchi et al. (2001) hypothesized that alpha-tocopherol is not only an antioxidant, but also a transcriptional regulator via its association with TAP.

Kempna et al. (2003) showed that in HeLa cells deletion of the C-terminal Golgi dynamics (GOLD) domain reduced SEC14L2 localization in the region surrounding the nucleus with some tubular sacs emerging. They suggested that the SEC14L2 GOLD domain may play a role in docking to other proteins or in intracellular transport of bound ligands. Using several assays, Kempna et al. (2003) demonstrated that SEC14L2 bound tocopherol, squalene, and phospholipids (phosphatidylcholine, phosphatidylinositol, phosphatidylglycerol). Although SEC14L2 bound phospholipids, it failed to complement an S. cerevisiae temperature-sensitive Sec14 allele in yeast. Using immunoprecipitation assays, Kempna et al. (2003) showed that SEC14L2 may interact with and regulate phosphatidylinositol 3-kinase activity, and SEC14L2 displayed low basal GTPase activity.

Saeed et al. (2015) found that SEC14L2 is necessary for hepatitis C virus replication in culture. Mechanistic studies suggested that SEC14L2 promotes HCV infection by enhancing vitamin E-mediated protection against lipid peroxidation.


Gene Structure

Zimmer et al. (2000) determined that the SEC14L2 gene contains 12 exons.


Mapping

By radiation hybrid analysis, Hirosawa et al. (1999) mapped the SEC14L2 gene to chromosome 22. By genomic sequence analysis, Zimmer et al. (2000) mapped the SEC14L2 gene to chromosome 22q12.1-qter.


REFERENCES

  1. Hirosawa, M., Nagase, T., Ishikawa, K., Kikuno, R., Nomura, N., Ohara, O.Characterization of cDNA clones selected by the GeneMark analysis from size-fractionated cDNA libraries from human brain. DNA Res. 6: 329-336, 1999. [PubMed: 10574461] [Full Text: https://doi.org/10.1093/dnares/6.5.329]

  2. Kempna, P., Zingg, J.-M., Ricciarelli, R., Hierl, M., Saxena, S., Azzi, A.Cloning of novel human Sec14p-like proteins: ligand binding and functional properties. Free Radic. Biol. Med. 34: 1458-1472, 2003. [PubMed: 12757856] [Full Text: https://doi.org/10.1016/s0891-5849(03)00173-4]

  3. Saeed, M., Andreo, U., Chung, H.-Y., Espiritu, C., Branch, A. D., Silva, J. M., Rice, C. M.SEC14L2 enables pan-genotype HCV replication in cell culture. Nature 524: 471-475, 2015. [PubMed: 26266980] [Full Text: https://doi.org/10.1038/nature14899]

  4. Yamauchi, J., Iwamoto, T., Kida, S., Masushige, S., Yamada, K., Esashi, T.Tocopherol-associated protein is a ligand-dependent transcriptional activator. Biochem. Biophys. Res. Commun. 285: 295-299, 2001. [PubMed: 11444841] [Full Text: https://doi.org/10.1006/bbrc.2001.5162]

  5. Zimmer, S., Stocker, A., Sarbolouki, M. N., Spycher, S. E., Sassoon, J., Azzi, A.A novel human tocopherol-associated protein: cloning, in vitro expression, and characterization. J. Biol. Chem. 275: 25672-25680, 2000. [PubMed: 10829015] [Full Text: https://doi.org/10.1074/jbc.M000851200]


Contributors:
Ada Hamosh - updated : 12/02/2015
Dorothy S. Reilly - updated : 5/28/2009

Creation Date:
Patricia A. Hartz : 2/11/2003

Edit History:
mgross : 06/29/2021
carol : 06/21/2019
alopez : 12/02/2015
wwang : 5/28/2009
terry : 7/20/2004
mgross : 2/11/2003



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OMIM® and Online Mendelian Inheritance in Man® are registered trademarks of the Johns Hopkins University.
Copyright® 1966-2025 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® 1966-2025 Johns Hopkins University.
Printed: April 1, 2025

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