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Gene Review

Luzp1  -  leucine zipper protein 1

Rattus norvegicus

Synonyms: Leucine zipper motif-containing protein, Leucine zipper protein 1, Luzp
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Disease relevance of Luzp1


High impact information on Luzp1

  • The recovered full-length cDNA encodes a 48 kDa protein, NEMO (NF-kappaB Essential MOdulator), which contains a putative leucine zipper motif [6].
  • These two proteins share the 145 C-terminal amino acids that contain the basic DNA-binding domain and the leucine zipper dimerization helix [7].
  • This family is characterized by leucine zipper domains compatible with that of the CCAAT/enhancer binding protein (C/EBP) [8].
  • It is shown here that cGKIalpha is targeted to the smooth muscle cell contractile apparatus by a leucine zipper interaction with the myosin-binding subunit (MBS) of myosin phosphatase [9].
  • A basic region of c-Myc is structurally related to the basic motifs of helix-loop-helix (HLH) and leucine zipper proteins, which provide sequence-specific DNA binding function [10].

Biological context of Luzp1

  • In addition to three leucine zipper motifs located at the NH2 terminus, there are three nuclear localization signals and a large number of putative Ser/Thr phosphorylation sites [11].
  • cDNA clones encoding a novel protein (LUZP) with three leucine zipper motifs were first identified from a murine bone marrow cDNA library [11].
  • Comparative mapping data suggest that the human homolog of Luzp will map to human chromosome 1p36 [11].
  • Interspecific backcross analyses have mapped Luzp to mouse chromosome 4 in proximity to Gpcr14 [11].
  • The arrangement of these related amino acid sequences led to the prediction of a new structural motif, termed the "leucine zipper," that plays a role in facilitating sequence-specific interaction between protein and DNA [12].

Anatomical context of Luzp1

  • Previously, we identified the basic leucine zipper transcription factor CCAAT/enhancer-binding protein beta (C/ EBPbeta) as an inhibitor of insulin gene transcription in pancreatic beta cells and showed that the expression of C/EBPbeta is upregulated in insulinoma-derived beta cell lines by sustained high glucose concentrations [13].
  • An RNA polymerase II complex containing all essential initiation factors binds to the activation domain of PAR leucine zipper transcription factor thyroid embryonic factor [14].
  • Nup107 is a novel nuclear pore complex protein that contains a leucine zipper [15].
  • Identification of Gasz, an evolutionarily conserved gene expressed exclusively in germ cells and encoding a protein with four ankyrin repeats, a sterile-alpha motif, and a basic leucine zipper [16].
  • The functional contributions of individual periods were studied in mutants in which periods 2-6 were individually deleted from rat striated muscle alphaalpha-tropomyosin or replaced with a leucine zipper sequence [17].

Associations of Luzp1 with chemical compounds

  • Directed mutagenesis of the cFos protein reveals that a leucine repeat structure is required for binding to cJun, in a manner consistent with the proposed function of the "leucine zipper." A novel domain adjacent to, but distinct from, the leucine repeat of cFos is required for DNA binding by cFos-cJun heterodimers [18].
  • Every member also bears a conserved cysteine residue at or near the carboxyl terminus, immediately following the leucine zipper, that at least in vitro allows efficient disulfide cross-linking between paired zipper helices [19].
  • A control mutant of dMax that contains a proline residue in the leucine-zipper region was unable to bind to N-Myc and did not revert the N-Myc-induced changes in cellular gene expression [20].
  • Involvement of unique leucine-zipper motif of PSD-Zip45 (Homer 1c/vesl-1L) in group 1 metabotropic glutamate receptor clustering [21].
  • However, the SREBPs are unique basic-helix-loop-helix leucine zipper proteins that not only bind to a subset of E-boxes but also to the direct repeat SRE-1 element of the low density lipoprotein receptor promoter as well as to variant sites present in the promoters for key enzymes of both cholesterol and fatty acid biosynthesis [22].

Regulatory relationships of Luzp1

  • The overexpression of the mutant of the EVH1 domain or deletion of the extreme C-terminal leucine zipper motif markedly suppressed the synaptic localization of endogenous shank but not PSD-95 or GKAP [23].

Other interactions of Luzp1

  • The EVH1 domain and extreme C-terminal leucine zipper motif of PSD-Zip45 were also critical for these events [23].
  • Computer analyses of the structure of the encoded Odf2 protein revealed an overall alpha-helical structure with two regions identical to the dimerization region of the leucine zipper motif [24].
  • Vesl-2 (354 amino acids) was highly related to Vesl-1L in that both contain EVH1- and PDZ-like domains at the N terminus (86% conservation) and an MCC (mutated in colorectal cancer)-like domain and a leucine zipper at the C terminus [25].
  • The c-Myc proto-oncogene is a basic helix-loop-helix leucine zipper (b/HLH/LZ) protein that participates in cellular growth and differentiation [26].
  • Identification of LRF-1, a leucine-zipper protein that is rapidly and highly induced in regenerating liver [27].

Analytical, diagnostic and therapeutic context of Luzp1

  • Site-directed mutagenesis studies reveal that AKAP15 directly interacts with the distal C terminus of the cardiac CaV1.2 channel via a leucine zipper-like motif [28].
  • The sequence analysis indicates that the novel protein, designated CELF, has a significant homology to C/EBP gene family proteins in the carboxyl-terminal part containing the basic region and the leucine zipper motif [29].
  • The thermal stabilities of three wild-type muscle alpha-TMs and nine chimeras, in which the second and/or sixth or ninth coding exons of one alpha-TM cDNA were replaced with exons from other alpha-TM cDNAs, with a sequence encoding the GCN4 leucine zipper or a random coil sequence, have been obtained using circular dichroism spectroscopy [30].
  • PKN, a novel protein kinase with a catalytic domain homologous to that of the protein kinase C (PKC) family and unique N-terminal leucine-zipper-like sequences, was identified by molecular cloning from a human hippocampus cDNA library [Mukai and Ono (1994) Biochem. Biophys. Res. Commun. 199, 897-904] [31].
  • Synthetic model peptides corresponding to the proposed leucine zipper-like coiled-coil regions of proBNP, proANP and their related N-terminal peptides were shown to be sufficient to induce oligomerisation when assessed on size exclusion HPLC [32].


  1. Intracellular leucine zipper interactions suggest c-Myc hetero-oligomerization. Dang, C.V., Barrett, J., Villa-Garcia, M., Resar, L.M., Kato, G.J., Fearon, E.R. Mol. Cell. Biol. (1991) [Pubmed]
  2. Expression of zinc finger immediate early genes in rat brain after permanent middle cerebral artery occlusion. Honkaniemi, J., States, B.A., Weinstein, P.R., Espinoza, J., Sharp, F.R. J. Cereb. Blood Flow Metab. (1997) [Pubmed]
  3. Hepatitis B virus X protein activates transcription by bypassing CREB phosphorylation, not by stabilizing bZIP-DNA complexes. Pflum, M.K., Schneider, T.L., Hall, D., Schepartz, A. Biochemistry (2001) [Pubmed]
  4. Dynamic changes in expression of myosin phosphatase in a model of portal hypertension. Payne, M.C., Zhang, H.Y., Shirasawa, Y., Koga, Y., Ikebe, M., Benoit, J.N., Fisher, S.A. Am. J. Physiol. Heart Circ. Physiol. (2004) [Pubmed]
  5. The possible inhibitory role of the leucine-zipper DNA binding protein c-fos in the regulation of hepatic gene expression after sepsis. Barke, R.A., Brady, P.S., Roy, S., Charboneau, R., Brady, L.J. Surgery (1992) [Pubmed]
  6. Complementation cloning of NEMO, a component of the IkappaB kinase complex essential for NF-kappaB activation. Yamaoka, S., Courtois, G., Bessia, C., Whiteside, S.T., Weil, R., Agou, F., Kirk, H.E., Kay, R.J., Israël, A. Cell (1998) [Pubmed]
  7. A liver-enriched transcriptional activator protein, LAP, and a transcriptional inhibitory protein, LIP, are translated from the same mRNA. Descombes, P., Schibler, U. Cell (1991) [Pubmed]
  8. IL-6DBP, a nuclear protein involved in interleukin-6 signal transduction, defines a new family of leucine zipper proteins related to C/EBP. Poli, V., Mancini, F.P., Cortese, R. Cell (1990) [Pubmed]
  9. Regulation of myosin phosphatase by a specific interaction with cGMP- dependent protein kinase Ialpha. Surks, H.K., Mochizuki, N., Kasai, Y., Georgescu, S.P., Tang, K.M., Ito, M., Lincoln, T.M., Mendelsohn, M.E. Science (1999) [Pubmed]
  10. Methylation-sensitive sequence-specific DNA binding by the c-Myc basic region. Prendergast, G.C., Ziff, E.B. Science (1991) [Pubmed]
  11. Identification, molecular characterization, and chromosomal localization of the cDNA encoding a novel leucine zipper motif-containing protein. Sun, D.S., Chang, A.C., Jenkins, N.A., Gilbert, D.J., Copeland, N.G., Chang, N.C. Genomics (1996) [Pubmed]
  12. The DNA binding domain of the rat liver nuclear protein C/EBP is bipartite. Landschulz, W.H., Johnson, P.F., McKnight, S.L. Science (1989) [Pubmed]
  13. Differential expression of the insulin gene transcriptional repressor CCAAT/enhancer-binding protein beta and transactivator islet duodenum homeobox-1 in rat pancreatic beta cells during the development of diabetes mellitus. Seufert, J., Weir, G.C., Habener, J.F. J. Clin. Invest. (1998) [Pubmed]
  14. An RNA polymerase II complex containing all essential initiation factors binds to the activation domain of PAR leucine zipper transcription factor thyroid embryonic factor. Ossipow, V., Fonjallaz, P., Schibler, U. Mol. Cell. Biol. (1999) [Pubmed]
  15. Nup107 is a novel nuclear pore complex protein that contains a leucine zipper. Radu, A., Blobel, G., Wozniak, R.W. J. Biol. Chem. (1994) [Pubmed]
  16. Identification of Gasz, an evolutionarily conserved gene expressed exclusively in germ cells and encoding a protein with four ankyrin repeats, a sterile-alpha motif, and a basic leucine zipper. Yan, W., Rajkovic, A., Viveiros, M.M., Burns, K.H., Eppig, J.J., Matzuk, M.M. Mol. Endocrinol. (2002) [Pubmed]
  17. Functions of tropomyosin's periodic repeats. Hitchcock-DeGregori, S.E., Song, Y., Greenfield, N.J. Biochemistry (2002) [Pubmed]
  18. Leucine repeats and an adjacent DNA binding domain mediate the formation of functional cFos-cJun heterodimers. Turner, R., Tjian, R. Science (1989) [Pubmed]
  19. A family of C/EBP-related proteins capable of forming covalently linked leucine zipper dimers in vitro. Williams, S.C., Cantwell, C.A., Johnson, P.F. Genes Dev. (1991) [Pubmed]
  20. A dominant-negative mutant of Max that inhibits sequence-specific DNA binding by Myc proteins. Billaud, M., Isselbacher, K.J., Bernards, R. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  21. Involvement of unique leucine-zipper motif of PSD-Zip45 (Homer 1c/vesl-1L) in group 1 metabotropic glutamate receptor clustering. Tadokoro, S., Tachibana, T., Imanaka, T., Nishida, W., Sobue, K. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  22. Two tandem binding sites for sterol regulatory element binding proteins are required for sterol regulation of fatty-acid synthase promoter. Magaña, M.M., Osborne, T.F. J. Biol. Chem. (1996) [Pubmed]
  23. Synaptic targeting of PSD-Zip45 (Homer 1c) and its involvement in the synaptic accumulation of F-actin. Usui, S., Konno, D., Hori, K., Maruoka, H., Okabe, S., Fujikado, T., Tano, Y., Sobue, K. J. Biol. Chem. (2003) [Pubmed]
  24. Identification and characterization of new cDNAs encoding outer dense fiber proteins of rat sperm. Brohmann, H., Pinnecke, S., Hoyer-Fender, S. J. Biol. Chem. (1997) [Pubmed]
  25. Novel members of the Vesl/Homer family of PDZ proteins that bind metabotropic glutamate receptors. Kato, A., Ozawa, F., Saitoh, Y., Fukazawa, Y., Sugiyama, H., Inokuchi, K. J. Biol. Chem. (1998) [Pubmed]
  26. c-Myc does not require max for transcriptional activity in PC-12 cells. Ribon, V., Leff, T., Saltiel, A.R. Mol. Cell. Neurosci. (1994) [Pubmed]
  27. Identification of LRF-1, a leucine-zipper protein that is rapidly and highly induced in regenerating liver. Hsu, J.C., Laz, T., Mohn, K.L., Taub, R. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  28. Beta-adrenergic regulation requires direct anchoring of PKA to cardiac CaV1.2 channels via a leucine zipper interaction with A kinase-anchoring protein 15. Hulme, J.T., Lin, T.W., Westenbroek, R.E., Scheuer, T., Catterall, W.A. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  29. Molecular characterization of transcription factors that bind to the cAMP responsive region of the substance P precursor gene. cDNA cloning of a novel C/EBP-related factor. Kageyama, R., Sasai, Y., Nakanishi, S. J. Biol. Chem. (1991) [Pubmed]
  30. The stability of tropomyosin, a two-stranded coiled-coil protein, is primarily a function of the hydrophobicity of residues at the helix-helix interface. Greenfield, N.J., Hitchcock-DeGregori, S.E. Biochemistry (1995) [Pubmed]
  31. Purification and characterization of a fatty acid-activated protein kinase (PKN) from rat testis. Kitagawa, M., Mukai, H., Shibata, H., Ono, Y. Biochem. J. (1995) [Pubmed]
  32. The amino terminal regions of proBNP and proANP oligomerise through leucine zipper-like coiled-coil motifs. Seidler, T., Pemberton, C., Yandle, T., Espiner, E., Nicholls, G., Richards, M. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
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