Entry - *607025 - MATERNAL EMBRYONIC LEUCINE ZIPPER KINASE; MELK - OMIM
 
* 607025

MATERNAL EMBRYONIC LEUCINE ZIPPER KINASE; MELK


Alternative titles; symbols

KIAA0175
HPK38


HGNC Approved Gene Symbol: MELK

Cytogenetic location: 9p13.2     Genomic coordinates (GRCh38): 9:36,572,895-36,677,682 (from NCBI)


TEXT

Cloning and Expression

Nagase et al. (1996) cloned MELK through the random sequencing of cDNA clones derived from a myeloid leukemic cell line. The deduced 651-amino acid protein shares 62% identity with Xenopus protein kinase p69Eg3. Northern blot analysis detected expression in placenta, kidney, thymus, testis, ovary, and intestine. Heyer et al. (1997) cloned mouse Melk by differential display PCR analysis using cDNA from the egg and 2- and 8-cell-stage embryo cDNA libraries as template. The deduced 644-amino acid protein contains an N-terminal serine/threonine kinase domain that includes all 12 typical catalytic subdomains, and a leucine zipper motif. The mouse and human proteins share 95% sequence identity in the kinase domain. Northern blot analysis in mouse detected restricted expression to spermatogonia in testis and to oocytes in ovary.

Hirose and Horvitz (2013) showed that the C. elegans Sp1 transcription factor SPTF3, which is most similar to human SP4 (600540), specifies the programmed cell deaths of at least 2 cells, the sisters of the pharyngeal M4 motor neuron and the AQR sensory neuron, by transcriptionally activating both caspase-dependent and -independent apoptotic pathways. SPTF3 directly drives the transcription of the gene egl-1, which encodes a BH3-only protein that promotes apoptosis through the activation of the CED3 caspase. In addition, SPTF3 directly drives the transcription of the AMP-activated protein kinase-related gene pig-1, which encodes a protein kinase closely related to mammalian MELK, and functions in apoptosis of the M4 sister and AQR sister independently of the pathway that activated CED3. Hirose and Horvitz (2013) concluded that a single transcription factor controls 2 distinct cell-killing programs that act in parallel to drive apoptosis.


Mapping

Using a panel of human/rodent hybrid cell lines, Nagase et al. (1996) mapped the MELK gene to chromosome 9. By SSCP analysis of mouse genomic DNA mapping panels, Heyer et al. (1997) mapped the mouse Melk gene to chromosome 4.


REFERENCES

  1. Heyer, B. S., Warsowe, J., Solter, D., Knowles, B. B., Ackerman, S. L. New member of the Snf1/AMPK kinase family, Melk, is expressed in the mouse egg and preimplantation embryo. Molec. Reprod. Dev. 47: 148-156, 1997. [PubMed: 9136115, related citations] [Full Text]

  2. Hirose, T., Horvitz, H. R. An Sp1 transcription factor coordinates caspase-dependent and -independent apoptotic pathways. Nature 500: 354-358, 2013. [PubMed: 23851392, images, related citations] [Full Text]

  3. Nagase, T., Seki, N., Ishikawa, K., Tanaka, A., Nomura, N. Prediction of the coding sequences of unidentified human genes. V. The coding sequences of 40 new genes (KIAA0161-KIAA0200) deduced by analysis of cDNA clones from human cell line KG-1. DNA Res. 3: 17-24, 1996. [PubMed: 8724849, related citations] [Full Text]


Contributors:
Ada Hamosh - updated : 10/03/2013
Creation Date:
Patricia A. Hartz : 6/7/2002
alopez : 10/03/2013
mgross : 5/27/2004
carol : 6/7/2002

* 607025

MATERNAL EMBRYONIC LEUCINE ZIPPER KINASE; MELK


Alternative titles; symbols

KIAA0175
HPK38


HGNC Approved Gene Symbol: MELK

Cytogenetic location: 9p13.2     Genomic coordinates (GRCh38): 9:36,572,895-36,677,682 (from NCBI)


TEXT

Cloning and Expression

Nagase et al. (1996) cloned MELK through the random sequencing of cDNA clones derived from a myeloid leukemic cell line. The deduced 651-amino acid protein shares 62% identity with Xenopus protein kinase p69Eg3. Northern blot analysis detected expression in placenta, kidney, thymus, testis, ovary, and intestine. Heyer et al. (1997) cloned mouse Melk by differential display PCR analysis using cDNA from the egg and 2- and 8-cell-stage embryo cDNA libraries as template. The deduced 644-amino acid protein contains an N-terminal serine/threonine kinase domain that includes all 12 typical catalytic subdomains, and a leucine zipper motif. The mouse and human proteins share 95% sequence identity in the kinase domain. Northern blot analysis in mouse detected restricted expression to spermatogonia in testis and to oocytes in ovary.

Hirose and Horvitz (2013) showed that the C. elegans Sp1 transcription factor SPTF3, which is most similar to human SP4 (600540), specifies the programmed cell deaths of at least 2 cells, the sisters of the pharyngeal M4 motor neuron and the AQR sensory neuron, by transcriptionally activating both caspase-dependent and -independent apoptotic pathways. SPTF3 directly drives the transcription of the gene egl-1, which encodes a BH3-only protein that promotes apoptosis through the activation of the CED3 caspase. In addition, SPTF3 directly drives the transcription of the AMP-activated protein kinase-related gene pig-1, which encodes a protein kinase closely related to mammalian MELK, and functions in apoptosis of the M4 sister and AQR sister independently of the pathway that activated CED3. Hirose and Horvitz (2013) concluded that a single transcription factor controls 2 distinct cell-killing programs that act in parallel to drive apoptosis.


Mapping

Using a panel of human/rodent hybrid cell lines, Nagase et al. (1996) mapped the MELK gene to chromosome 9. By SSCP analysis of mouse genomic DNA mapping panels, Heyer et al. (1997) mapped the mouse Melk gene to chromosome 4.


REFERENCES

  1. Heyer, B. S., Warsowe, J., Solter, D., Knowles, B. B., Ackerman, S. L. New member of the Snf1/AMPK kinase family, Melk, is expressed in the mouse egg and preimplantation embryo. Molec. Reprod. Dev. 47: 148-156, 1997. [PubMed: 9136115] [Full Text: https://doi.org/10.1002/(SICI)1098-2795(199706)47:2<148::AID-MRD4>3.0.CO;2-M]

  2. Hirose, T., Horvitz, H. R. An Sp1 transcription factor coordinates caspase-dependent and -independent apoptotic pathways. Nature 500: 354-358, 2013. [PubMed: 23851392] [Full Text: https://doi.org/10.1038/nature12329]

  3. Nagase, T., Seki, N., Ishikawa, K., Tanaka, A., Nomura, N. Prediction of the coding sequences of unidentified human genes. V. The coding sequences of 40 new genes (KIAA0161-KIAA0200) deduced by analysis of cDNA clones from human cell line KG-1. DNA Res. 3: 17-24, 1996. [PubMed: 8724849] [Full Text: https://doi.org/10.1093/dnares/3.1.17]


Contributors:
Ada Hamosh - updated : 10/03/2013

Creation Date:
Patricia A. Hartz : 6/7/2002

Edit History:
alopez : 10/03/2013
mgross : 5/27/2004
carol : 6/7/2002