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Gene Review

LUZP1  -  leucine zipper protein 1

Homo sapiens

Synonyms: LUZP, Leucine zipper protein 1
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Disease relevance of LUZP1

  • Acute lymphoblastic leukemias (ALL) pre-B phenotype produce a E2A/PBX fusion protein that possesses the leucine zipper of E2A with the homeodomain of PBX [1].
  • The structure provides insights into ZEBRA's broad target site specificity, preferential activation of specific EBV promoters in their methylated state, ability to dimerize despite lacking a leucine zipper motif, and failure to heterodimerize with cellular bZIP proteins [2].
  • In this study, we define the cellular mechanism leading to the disease and show that maternal autoantibodies directed to a specific epitope within the leucine zipper amino acid sequence 200-239 (p200) of the Ro52 protein correlate with prolongation of fetal atrioventricular (AV) time and heart block [3].
  • Disruption of nuclear factor-erythroid 2-related factor 2 (Nrf2), a basic leucine zipper transcription factor that regulates redox balance and stress response, dramatically increased the mortality of mice in response to endotoxin- and cecal ligation and puncture-induced septic shock [4].
  • Multiple cDNA clones encoding nuclear proteins that bind to the tax-dependent enhancer of HTLV-1: all contain a leucine zipper structure and basic amino acid domain [5].

Psychiatry related information on LUZP1

  • Par-4 (prostate apoptosis response-4) is a leucine zipper protein involved in neuronal degeneration and cholinergic signaling in Alzheimer's disease [6].

High impact information on LUZP1

  • Both quasisymmetric heterodimers resemble the symmetric Max homodimer, albeit with marked structural differences in the coiled-coil leucine zipper regions that explain preferential homo- and heteromeric dimerization of these three evolutionarily related DNA-binding proteins [7].
  • ATM also contains a proline-rich region and a leucine zipper, both of which implicate this protein in signal transduction [8].
  • While the interactions between IKKalpha and IKKbeta may be mediated through their leucine zipper motifs, their helix-loop-helix motifs may be involved in interactions with essential regulatory subunits [9].
  • Here we report that Prf encodes a protein with leucine-zipper, nucleotide-binding, and leucine-rich repeat motifs, as are found in a number of resistance gene products from other plants. prf mutant alleles (4) were found to carry alterations within the Prf coding sequence [10].
  • Mutant analysis reveals that the ligand binding and DNA binding domains of GR and the region including the leucine zipper of c-Jun are required for repression [11].

Chemical compound and disease context of LUZP1


Biological context of LUZP1

  • The complete open reading frame of LUZP is 1067 amino acids [17].
  • Mutant c-Jun recombinants, in which the activation domains were deleted, still remained inhibitory, but a specific mutation in the leucine zipper, which changes the alignment of Jun with its dimerization partner, caused a reversal of its effect on the target MLC-2v promoter [18].
  • A Fos protein containing the Jun leucine zipper forms a homodimer which binds to the AP1 binding site [19].
  • We cloned the gene ces-2, which is required to activate programmed cell death in the sister cells of the serotoninergic neurosecretory motor (NSM) neurons, and found that ces-2 encodes a basic region leucine-zipper (bZIP) transcription factor [20].
  • Activating transcription factor-2 (ATF-2) is a basic region leucine zipper protein whose DNA target sequence is the widely distributed cAMP response element (CRE) [21].

Anatomical context of LUZP1

  • Based on these findings, we propose that in chicken cardiac myocytes, the regulation of MLC-2v promoter by Jun may occur via its interaction with other proteins, possibly of the leucine zipper family [18].
  • 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 [22].
  • Finally, we demonstrate that the leucine zipper of C/EBP alpha participates in determining the cell type specificity of albumin promoter activation, as it exerts a strong negative effect on albumin promoter activation in the nonhepatic HeLa cell line but not in HepG2 cells [23].
  • The PRP9 protein is a yeast splicing factor implicated in the early steps of spliceosome assembly whose sequence contains an amino-terminal putative leucine zipper structure and two carboxy-terminal motifs reminiscent of zinc fingers [24].
  • P40 is the protein encoded by the first open reading frame (ORF1) of the human LINE-1 (L1Hs) retrotransposon; it is 338 amino acids long, has a leucine zipper motif and has been found in human teratocarcinoma cell lines and some tumor cells [25].

Associations of LUZP1 with chemical compounds


Physical interactions of LUZP1


Enzymatic interactions of LUZP1

  • The leucine zipper dimerization domains were then cleaved from the assembled HLA-DR2/MBP peptide complex with V8 protease, and the protein was further purified by anion-exchange HPLC [36].

Regulatory relationships of LUZP1

  • The human HSF1 mRNA is constitutively expressed in HeLa cells under nonshock conditions and encodes a protein with four conserved leucine zipper motifs [37].
  • Nrf-2 has previously been shown to regulate transcription of other genes through interactions between its C-terminal leucine zipper and the leucine-zipper region of other members of the small Maf protein family (the term "Maf" is derived from MusculoAponeurotic-Fibrosarcoma virus) [38].
  • The activator protein 1 (AP-1) transcription factor is composed of heterodimers of the Fos/activating transcription factor (ATF) and Jun subfamilies of basic-region leucine-zipper (B-ZIP) proteins [39].
  • BEF stimulates DNA binding by recognizing the unfolded leucine zipper and promoting the folding of bZIP monomers to dimers; the elevated concentration of the bZIP dimer then drives the DNA binding reaction [40].
  • KARP-1: a novel leucine zipper protein expressed from the Ku86 autoantigen locus is implicated in the control of DNA-dependent protein kinase activity [41].

Other interactions of LUZP1


Analytical, diagnostic and therapeutic context of LUZP1


  1. Chromosomal translocations in lymphoid malignancies reveal novel proto-oncogenes. Korsmeyer, S.J. Annu. Rev. Immunol. (1992) [Pubmed]
  2. Structural basis of lytic cycle activation by the Epstein-Barr virus ZEBRA protein. Petosa, C., Morand, P., Baudin, F., Moulin, M., Artero, J.B., Müller, C.W. Mol. Cell (2006) [Pubmed]
  3. Ro/SSA autoantibodies directly bind cardiomyocytes, disturb calcium homeostasis, and mediate congenital heart block. Salomonsson, S., Sonesson, S.E., Ottosson, L., Muhallab, S., Olsson, T., Sunnerhagen, M., Kuchroo, V.K., Thorén, P., Herlenius, E., Wahren-Herlenius, M. J. Exp. Med. (2005) [Pubmed]
  4. Nrf2 is a critical regulator of the innate immune response and survival during experimental sepsis. Thimmulappa, R.K., Lee, H., Rangasamy, T., Reddy, S.P., Yamamoto, M., Kensler, T.W., Biswal, S. J. Clin. Invest. (2006) [Pubmed]
  5. Multiple cDNA clones encoding nuclear proteins that bind to the tax-dependent enhancer of HTLV-1: all contain a leucine zipper structure and basic amino acid domain. Yoshimura, T., Fujisawa, J., Yoshida, M. EMBO J. (1990) [Pubmed]
  6. Par-4 inhibits choline uptake by interacting with CHT1 and reducing its incorporation on the plasma membrane. Xie, J., Guo, Q. J. Biol. Chem. (2004) [Pubmed]
  7. X-ray structures of Myc-Max and Mad-Max recognizing DNA. Molecular bases of regulation by proto-oncogenic transcription factors. Nair, S.K., Burley, S.K. Cell (2003) [Pubmed]
  8. ATM associates with and phosphorylates p53: mapping the region of interaction. Khanna, K.K., Keating, K.E., Kozlov, S., Scott, S., Gatei, M., Hobson, K., Taya, Y., Gabrielli, B., Chan, D., Lees-Miller, S.P., Lavin, M.F. Nat. Genet. (1998) [Pubmed]
  9. The IkappaB kinase complex (IKK) contains two kinase subunits, IKKalpha and IKKbeta, necessary for IkappaB phosphorylation and NF-kappaB activation. Zandi, E., Rothwarf, D.M., Delhase, M., Hayakawa, M., Karin, M. Cell (1997) [Pubmed]
  10. Tomato Prf is a member of the leucine-rich repeat class of plant disease resistance genes and lies embedded within the Pto kinase gene cluster. Salmeron, J.M., Oldroyd, G.E., Rommens, C.M., Scofield, S.R., Kim, H.S., Lavelle, D.T., Dahlbeck, D., Staskawicz, B.J. Cell (1996) [Pubmed]
  11. Functional antagonism between oncoprotein c-Jun and the glucocorticoid receptor. Schüle, R., Rangarajan, P., Kliewer, S., Ransone, L.J., Bolado, J., Yang, N., Verma, I.M., Evans, R.M. Cell (1990) [Pubmed]
  12. Propensity for a leucine zipper-like domain of human immunodeficiency virus type 1 gp41 to form oligomers correlates with a role in virus-induced fusion rather than assembly of the glycoprotein complex. Wild, C., Dubay, J.W., Greenwell, T., Baird, T., Oas, T.G., McDanal, C., Hunter, E., Matthews, T. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  13. T21/DP107, A synthetic leucine zipper-like domain of the HIV-1 envelope gp41, attracts and activates human phagocytes by using G-protein-coupled formyl peptide receptors. Su, S.B., Gao, J., Gong, W., Dunlop, N.M., Murphy, P.M., Oppenheim, J.J., Wang, J.M. J. Immunol. (1999) [Pubmed]
  14. Differentially androgen-modulated genes in ovarian epithelial cells from BRCA mutation carriers and control patients predict ovarian cancer survival and disease progression. Motamed-Khorasani, A., Jurisica, I., Letarte, M., Shaw, P.A., Parkes, R.K., Zhang, X., Evangelou, A., Rosen, B., Murphy, K.J., Brown, T.J. Oncogene (2007) [Pubmed]
  15. Mutations in the leucine zipper of the human immunodeficiency virus type 1 transmembrane glycoprotein affect fusion and infectivity. Dubay, J.W., Roberts, S.J., Brody, B., Hunter, E. J. Virol. (1992) [Pubmed]
  16. Proline affects oligomerization of a coiled coil by inducing a kink in a long helix. Chang, D.K., Cheng, S.F., Trivedi, V.D., Lin, K.L. J. Struct. Biol. (1999) [Pubmed]
  17. 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]
  18. Modulation of MLC-2v gene expression by AP-1: complex regulatory role of Jun in cardiac myocytes. Goswami, S.K., Shafiq, S., Siddiqui, M.A. Mol. Cell. Biochem. (2001) [Pubmed]
  19. A Fos protein containing the Jun leucine zipper forms a homodimer which binds to the AP1 binding site. Neuberg, M., Adamkiewicz, J., Hunter, J.B., Müller, R. Nature (1989) [Pubmed]
  20. Transcriptional regulator of programmed cell death encoded by Caenorhabditis elegans gene ces-2. Metzstein, M.M., Hengartner, M.O., Tsung, N., Ellis, R.E., Horvitz, H.R. Nature (1996) [Pubmed]
  21. Chondrodysplasia and neurological abnormalities in ATF-2-deficient mice. Reimold, A.M., Grusby, M.J., Kosaras, B., Fries, J.W., Mori, R., Maniwa, S., Clauss, I.M., Collins, T., Sidman, R.L., Glimcher, M.J., Glimcher, L.H. Nature (1996) [Pubmed]
  22. 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]
  23. Three levels of functional interaction determine the activity of CCAAT/enhancer binding protein-alpha on the serum albumin promoter. Nerlov, C., Ziff, E.B. Genes Dev. (1994) [Pubmed]
  24. Interactions between PRP9 and SPP91 splicing factors identify a protein complex required in prespliceosome assembly. Legrain, P., Chapon, C., Galisson, F. Genes Dev. (1993) [Pubmed]
  25. Cytoplasmic ribonucleoprotein complexes containing human LINE-1 protein and RNA. Hohjoh, H., Singer, M.F. EMBO J. (1996) [Pubmed]
  26. Calcium-regulated phosphorylation within the leucine zipper of C/EBP beta. Wegner, M., Cao, Z., Rosenfeld, M.G. Science (1992) [Pubmed]
  27. A plant leucine zipper protein that recognizes an abscisic acid response element. Guiltinan, M.J., Marcotte, W.R., Quatrano, R.S. Science (1990) [Pubmed]
  28. JunB differs from c-Jun in its DNA-binding and dimerization domains, and represses c-Jun by formation of inactive heterodimers. Deng, T., Karin, M. Genes Dev. (1993) [Pubmed]
  29. Molecular characterization of two human autoantigens: unique cDNAs encoding 95- and 160-kD proteins of a putative family in the Golgi complex. Fritzler, M.J., Hamel, J.C., Ochs, R.L., Chan, E.K. J. Exp. Med. (1993) [Pubmed]
  30. A new mouse gene, SRG3, related to the SWI3 of Saccharomyces cerevisiae, is required for apoptosis induced by glucocorticoids in a thymoma cell line. Jeon, S.H., Kang, M.G., Kim, Y.H., Jin, Y.H., Lee, C., Chung, H.Y., Kwon, H., Park, S.D., Seong, R.H. J. Exp. Med. (1997) [Pubmed]
  31. The MLL fusion partner AF10 binds GAS41, a protein that interacts with the human SWI/SNF complex. Debernardi, S., Bassini, A., Jones, L.K., Chaplin, T., Linder, B., de Bruijn, D.R., Meese, E., Young, B.D. Blood (2002) [Pubmed]
  32. Molecular cloning of cellular genes encoding retinoblastoma-associated proteins: identification of a gene with properties of the transcription factor E2F. Shan, B., Zhu, X., Chen, P.L., Durfee, T., Yang, Y., Sharp, D., Lee, W.H. Mol. Cell. Biol. (1992) [Pubmed]
  33. MRGX is a novel transcriptional regulator that exhibits activation or repression of the B-myb promoter in a cell type-dependent manner. Tominaga, K., Leung, J.K., Rookard, P., Echigo, J., Smith, J.R., Pereira-Smith, O.M. J. Biol. Chem. (2003) [Pubmed]
  34. Purification of an interleukin-1 beta converting enzyme-related cysteine protease that cleaves sterol regulatory element-binding proteins between the leucine zipper and transmembrane domains. Wang, X., Pai, J.T., Wiedenfeld, E.A., Medina, J.C., Slaughter, C.A., Goldstein, J.L., Brown, M.S. J. Biol. Chem. (1995) [Pubmed]
  35. YY-1 and c-Jun transcription factors participate in the repression of the human involucrin promoter. Alvarez-Salas, L.M., Benitez-Hess, M.L., Dipaolo, J.A. Int. J. Oncol. (2005) [Pubmed]
  36. Expression and crystallization of the complex of HLA-DR2 (DRA, DRB1*1501) and an immunodominant peptide of human myelin basic protein. Gauthier, L., Smith, K.J., Pyrdol, J., Kalandadze, A., Strominger, J.L., Wiley, D.C., Wucherpfennig, K.W. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  37. Molecular cloning and expression of a human heat shock factor, HSF1. Rabindran, S.K., Giorgi, G., Clos, J., Wu, C. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  38. Characterization of the interaction between the transcription factors human polyamine modulated factor (PMF-1) and NF-E2-related factor 2 (Nrf-2) in the transcriptional regulation of the spermidine/spermine N1-acetyltransferase (SSAT) gene. Wang, Y., Devereux, W., Stewart, T.M., Casero, R.A. Biochem. J. (2001) [Pubmed]
  39. Regulation and composition of activator protein 1 (AP-1) transcription factors controlling collagenase and c-Jun promoter activities. Steinmüller, L., Cibelli, G., Moll, J.R., Vinson, C., Thiel, G. Biochem. J. (2001) [Pubmed]
  40. A human nuclear-localized chaperone that regulates dimerization, DNA binding, and transcriptional activity of bZIP proteins. Virbasius, C.M., Wagner, S., Green, M.R. Mol. Cell (1999) [Pubmed]
  41. KARP-1: a novel leucine zipper protein expressed from the Ku86 autoantigen locus is implicated in the control of DNA-dependent protein kinase activity. Myung, K., He, D.M., Lee, S.E., Hendrickson, E.A. EMBO J. (1997) [Pubmed]
  42. TFE3: a helix-loop-helix protein that activates transcription through the immunoglobulin enhancer muE3 motif. Beckmann, H., Su, L.K., Kadesch, T. Genes Dev. (1990) [Pubmed]
  43. ATF6 activated by proteolysis binds in the presence of NF-Y (CBF) directly to the cis-acting element responsible for the mammalian unfolded protein response. Yoshida, H., Okada, T., Haze, K., Yanagi, H., Yura, T., Negishi, M., Mori, K. Mol. Cell. Biol. (2000) [Pubmed]
  44. The proto-oncogene HLF and the related basic leucine zipper protein TEF display highly similar DNA-binding and transcriptional regulatory properties. Hunger, S.P., Li, S., Fall, M.Z., Naumovski, L., Cleary, M.L. Blood (1996) [Pubmed]
  45. The leucine zipper of NRL interacts with the CRX homeodomain. A possible mechanism of transcriptional synergy in rhodopsin regulation. Mitton, K.P., Swain, P.K., Chen, S., Xu, S., Zack, D.J., Swaroop, A. J. Biol. Chem. (2000) [Pubmed]
  46. A novel class of zinc finger/leucine zipper genes identified from the molecular cloning of the t(10;11) translocation in acute leukemia. Chaplin, T., Ayton, P., Bernard, O.A., Saha, V., Della Valle, V., Hillion, J., Gregorini, A., Lillington, D., Berger, R., Young, B.D. Blood (1995) [Pubmed]
  47. A designed system for assessing how sequence affects alpha to beta conformational transitions in proteins. Ciani, B., Hutchinson, E.G., Sessions, R.B., Woolfson, D.N. J. Biol. Chem. (2002) [Pubmed]
  48. Sex-determining region Y-related protein SOX13 is a diabetes autoantigen expressed in pancreatic islets. Kasimiotis, H., Myers, M.A., Argentaro, A., Mertin, S., Fida, S., Ferraro, T., Olsson, J., Rowley, M.J., Harley, V.R. Diabetes (2000) [Pubmed]
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