Alternative titles; symbols
HGNC Approved Gene Symbol: MARCKSL1
Cytogenetic location: 1p35.1 Genomic coordinates (GRCh38): 1:32,333,839-32,336,233 (from NCBI)
Umekage and Kato (1991) identified a cDNA with homology to MARCKS (PKCSL; 177061) among mouse brain cDNAs with specific brain expression patterns. The myristoylated, alanine-rich protein MARCKS is a widely expressed, prominent substrate for protein kinase C (see 176960), a key enzyme of intracellular signal transduction. The predicted 200-amino acid protein, which they called F52, shares 52% amino acid identity with bovine MARCKS. The similarity between the 2 proteins is found in the consensus myristoylation sequence near the N-terminus and in the 25-amino acid protein kinase C phosphorylation site domain. F52 has a similar amino acid composition to MARCKS, although its alanine content is not as high. It is distributed throughout the mouse brain in a pattern that is distinct from that of MARCKS.
By screening a genomic library with portions of the Mrp cDNA, Stumpo et al. (1998) isolated the human homolog, which they designated MLP for 'MARCKS-like protein.' They reported that the sequences of the mouse and human promoters were 71% identical over 433 bp. A transgene containing this 433-bp fragment from mouse linked to a reporter Mrp beta-galactosidase gene produced normal patterns of Mrp expression in the developing mouse embryo.
Using Northern hybridization, Lobach et al. (1993) observed Mrp expression in various mouse tissues, with highest levels in testis and uterus.
Lobach et al. (1993) reported that the mouse F52, or Mrp, gene contains a single intron at a position exactly analogous to that of the single intron in mouse, cow, and human MARCKS.
By analysis of an interspecific backcross, Lobach et al. (1993) mapped the Mrp gene to a position on mouse chromosome 4 that was closely linked to the Lck (153390) locus. Based on homology of synteny, they predicted that the human homolog would map to chromosome 1p35-p32. Using somatic cell hybrid analysis and fluorescence in situ hybridization, Stumpo et al. (1998) confirmed that the human MLP gene maps to 1p34.
Bjorkblom et al. (2012) found that Jnk (see 601158) phosphorylated mouse Marcksl1 on C-terminal serine and threonine residues. Expression of a phosphomimetic Marcksl1 mutant in neonatal rat cortical neurons, mouse embryonic fibroblasts, or human PC3 prostate carcinoma cells induced F-actin bundling and inhibited cell migration. Expression of a nonphosphorylatable Marcksl1 mutant or knockdown of Marcksl1 induced migration in neurons and PC3 cells.
Sugiura et al. (2016) found that axolotl Mlp was released extracellularly following appendage amputation and induced initial cell-cycle responses during appendage regeneration.
Wu et al. (1996) used gene targeting to generate Mrp-deficient mice. They observed severe neural tube defects (NTD) including exencephaly, spina bifida, and tail flexion anomaly in approximately 60% of the homozygous mutants and in approximately 10% of heterozygous animals. The homozygous mutants without exencephaly survived despite brain abnormalities, which appear to occur secondarily to the NTD. Wu et al. (1996) suggested that mutations in Mrp result in isolated NTD and therefore may provide an animal model for common human NTD.
Bjorkblom, B., Padzik, A., Mohammad, H., Westerlund, N., Komulainen, E., Hollos, P., Parviainen, L., Papageorgiou, A. C., Iljin, K., Kallioniemi, O., Kallajoki, M., Courtney, M. J., Magard, M., James, P., Coffey, E. T. c-Jun N-terminal kinase phosphorylation of MARCKSL1 determines actin stability and migration in neurons and in cancer cells. Molec. Cell. Biol. 32: 3513-3526, 2012. [PubMed: 22751924] [Full Text: https://doi.org/10.1128/MCB.00713-12]
Lobach, D. F., Rochelle, J. M., Watson, M. L., Seldin, M. F., Blackshear, P. J. Nucleotide sequence, expression, and chromosomal mapping of Mrp and mapping of five related sequences. Genomics 17: 194-204, 1993. [PubMed: 8406449] [Full Text: https://doi.org/10.1006/geno.1993.1301]
Stumpo, D. J., Eddy, R. L., Jr., Haley, L. L., Sait, S., Shows, T. B., Lai, W. S., Young, W. S., III, Speer, M. C., Dehejia, A., Polymeropoulos, M., Blackshear, P. J. Promoter sequence, expression, and fine chromosomal mapping of the human gene (MLP) encoding the MARCKS-like protein: identification of neighboring and linked polymorphic loci for MLP and MACS and use in the evaluation of human neural tube defects. Genomics 49: 253-264, 1998. [PubMed: 9598313] [Full Text: https://doi.org/10.1006/geno.1998.5247]
Sugiura, T., Wang, H., Barsacchi, R., Simon, A., Tanaka, E. M. MARCKS-like protein is an initiating molecule in axolotl appendage regeneration. Nature 531: 237-240, 2016. [PubMed: 26934225] [Full Text: https://doi.org/10.1038/nature16974]
Umekage, T., Kato, K. A mouse brain cDNA encodes a novel protein with the protein kinase C phosphorylation site domain common to MARCKS. FEBS Lett. 286: 147-151, 1991. [PubMed: 1864362] [Full Text: https://doi.org/10.1016/0014-5793(91)80961-2]
Wu, M., Chen, D. F., Sasaoka, T., Tonegawa, S. Neural tube defects and abnormal brain development in F52-deficient mice. Proc. Nat. Acad. Sci. 93: 2110-2115, 1996. [PubMed: 8700893] [Full Text: https://doi.org/10.1073/pnas.93.5.2110]