Entry - *300361 - NERVE GROWTH FACTOR RECEPTOR-ASSOCIATED PROTEIN 1; NGFRAP1 - OMIM

 
 
* 300361

NERVE GROWTH FACTOR RECEPTOR-ASSOCIATED PROTEIN 1; NGFRAP1


Alternative titles; symbols

NGFR-ASSOCIATED PROTEIN 1
p75(NTR)-ASSOCIATED CELL DEATH EXECUTOR; NADE
BRAIN-EXPRESSED X-LINKED GENE 3; BEX3


HGNC Approved Gene Symbol: BEX3

Cytogenetic location: Xq22.2   Genomic coordinates (GRCh38) : X:103,376,323-103,378,164 (from NCBI)


TEXT

▼ Cloning and Expression

The C-terminal cytoplasmic domain of p75(NTR) (NGFR; 162010) has a type-2 death domain. However, TRAF (e.g., TRAF6; 602355)-like proteins that interact with this domain do not affect NGF (162030)-dependent apoptosis. Using a yeast 2-hybrid screen with the cytosolic domain of p75(NTR) as bait, Mukai et al. (2000) obtained cDNAs encoding mouse and human p75(NTR)-associated cell death executor, or NADE. Human NADE is identical to the HGR74 cDNA cloned by Rapp et al. (1990) from an ovarian granulosa cDNA library. HGR74 was expressed in testis, prostate, seminal vesicle, and ovarian granulosa cells (Rapp et al., 1990). By sequence analysis, Mukai et al. (2000) predicted that the 111-amino acid NADE protein has a leucine-rich nuclear export signal (NES) and 2 ubiquitination sequence boxes. Western blot analysis showed expression of mouse Nade only after proteasome inhibition, implying that native Nade is modified by the ubiquitin conjugating system.


▼ Gene Function

Using immunofluorescence microscopy, Rapp et al. (1990) demonstrated expression of wildtype Nade, but not Nade carrying leu94-to-ala and leu97-to-ala mutations in the NES, in the cytoplasm. GST pull-down analysis indicated that the C terminus of Nade binds to the cytoplasmic cell death domain of p75(NTR). Coimmunoprecipitation analysis showed that NGF induces interaction of NADE and p75(NTR). Tunel analysis determined that NGF, but not other neurotrophins, could induce apoptosis in cells expressing NADE and p75(NTR). NGF-treated cells expressing NADE and p75(NTR) processed CASP2 (600639) and CASP3 (600636) to their active forms. Confocal microscopy established that most NGF-treated oligodendrocytes underwent apoptosis and expressed NADE.


▼ Mapping

Scott (2001) mapped the NGFRAP1 gene to Xq22.1-q23 based on sequence similarity between the NGFRAP1 sequence and the chromosome X clone RP13-349O20 (GenBank AL606763).

▼ REFERENCES

  1. Mukai, J., Hachiya, T., Shoji-Hoshino, S., Kimura, M. T., Nadano, D., Suvanto, P., Hanaoka, T., Li, Y., Irie, S., Greene, L. A., Sato, T.-A. NADE, a p75NTR-associated cell death executor, is involved in signal transduction mediated by the common neurotrophin receptor p75NTR. J. Biol. Chem. 275: 17566-17570, 2000. [PubMed: 10764727, related citations] [Full Text]

  2. Rapp, G., Freudenstein, J., Klaudiny, J., Mucha, J., Wempe, F., Zimmer, M., Scheit, K. H. Characterization of three abundant mRNAs from human ovarian granulosa cells. DNA Cell Biol. 9: 479-485, 1990. [PubMed: 2171551, related citations] [Full Text]

  3. Scott, A. F. Personal Communication. Baltimore, Md. 10/8/2001.


Contributors:
Alan F. Scott - updated : 10/10/2001
Creation Date:
Paul J. Converse : 10/9/2001
Edit History:
carol : 02/04/2008
carol : 9/24/2007
carol : 11/24/2001
joanna : 10/10/2001

* 300361

NERVE GROWTH FACTOR RECEPTOR-ASSOCIATED PROTEIN 1; NGFRAP1


Alternative titles; symbols

NGFR-ASSOCIATED PROTEIN 1
p75(NTR)-ASSOCIATED CELL DEATH EXECUTOR; NADE
BRAIN-EXPRESSED X-LINKED GENE 3; BEX3


HGNC Approved Gene Symbol: BEX3

Cytogenetic location: Xq22.2   Genomic coordinates (GRCh38) : X:103,376,323-103,378,164 (from NCBI)


TEXT

Cloning and Expression

The C-terminal cytoplasmic domain of p75(NTR) (NGFR; 162010) has a type-2 death domain. However, TRAF (e.g., TRAF6; 602355)-like proteins that interact with this domain do not affect NGF (162030)-dependent apoptosis. Using a yeast 2-hybrid screen with the cytosolic domain of p75(NTR) as bait, Mukai et al. (2000) obtained cDNAs encoding mouse and human p75(NTR)-associated cell death executor, or NADE. Human NADE is identical to the HGR74 cDNA cloned by Rapp et al. (1990) from an ovarian granulosa cDNA library. HGR74 was expressed in testis, prostate, seminal vesicle, and ovarian granulosa cells (Rapp et al., 1990). By sequence analysis, Mukai et al. (2000) predicted that the 111-amino acid NADE protein has a leucine-rich nuclear export signal (NES) and 2 ubiquitination sequence boxes. Western blot analysis showed expression of mouse Nade only after proteasome inhibition, implying that native Nade is modified by the ubiquitin conjugating system.


Gene Function

Using immunofluorescence microscopy, Rapp et al. (1990) demonstrated expression of wildtype Nade, but not Nade carrying leu94-to-ala and leu97-to-ala mutations in the NES, in the cytoplasm. GST pull-down analysis indicated that the C terminus of Nade binds to the cytoplasmic cell death domain of p75(NTR). Coimmunoprecipitation analysis showed that NGF induces interaction of NADE and p75(NTR). Tunel analysis determined that NGF, but not other neurotrophins, could induce apoptosis in cells expressing NADE and p75(NTR). NGF-treated cells expressing NADE and p75(NTR) processed CASP2 (600639) and CASP3 (600636) to their active forms. Confocal microscopy established that most NGF-treated oligodendrocytes underwent apoptosis and expressed NADE.


Mapping

Scott (2001) mapped the NGFRAP1 gene to Xq22.1-q23 based on sequence similarity between the NGFRAP1 sequence and the chromosome X clone RP13-349O20 (GenBank AL606763).

REFERENCES

  1. Mukai, J., Hachiya, T., Shoji-Hoshino, S., Kimura, M. T., Nadano, D., Suvanto, P., Hanaoka, T., Li, Y., Irie, S., Greene, L. A., Sato, T.-A. NADE, a p75NTR-associated cell death executor, is involved in signal transduction mediated by the common neurotrophin receptor p75NTR. J. Biol. Chem. 275: 17566-17570, 2000. [PubMed: 10764727] [Full Text: https://doi.org/10.1074/jbc.C000140200]

  2. Rapp, G., Freudenstein, J., Klaudiny, J., Mucha, J., Wempe, F., Zimmer, M., Scheit, K. H. Characterization of three abundant mRNAs from human ovarian granulosa cells. DNA Cell Biol. 9: 479-485, 1990. [PubMed: 2171551] [Full Text: https://doi.org/10.1089/dna.1990.9.479]

  3. Scott, A. F. Personal Communication. Baltimore, Md. 10/8/2001.


Contributors:
Alan F. Scott - updated : 10/10/2001

Creation Date:
Paul J. Converse : 10/9/2001

Edit History:
carol : 02/04/2008
carol : 9/24/2007
carol : 11/24/2001
joanna : 10/10/2001



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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: Nov. 16, 2024