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Gene Review

MANF  -  mesencephalic astrocyte-derived...

Homo sapiens

Synonyms: ARMET, ARP, Arginine-rich protein, Mesencephalic astrocyte-derived neurotrophic factor, Protein ARMET
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Disease relevance of ARMET


High impact information on ARMET


Chemical compound and disease context of ARMET


Biological context of ARMET


Anatomical context of ARMET


Associations of ARMET with chemical compounds

  • Both binding activity and heparin precipitability appeared to correlate with an increase in arginine-rich apoprotein (apo-E) in the active H.D.L. subfraction [25].
  • In the ER, an estrogen-inducible p-NLS was found in the hormone binding domain (HBD), in addition to three lysine/arginine-rich motifs resembling prototype constitutive nuclear localization signals (NLSs) [26].
  • The larger kink (43 degrees ) is induced by a novel mechanism, 'phosphate bridging by an arginine-rich helix': the recognition helix with an arginine cluster is inserted perpendicularly into the major groove and bridges the groove through direct interactions with the phosphate groups [27].
  • The gene codes for a 34.5 kd protein which contains glycine/arginine rich sequence repeats at the amino terminus similar to those found in other nucleolar proteins [28].
  • Estrogen withdrawal promptly restored the type III pattern with its abnormal enrichment of VLD lipoproteins with apolipoprotein E (the arginine-rich peptide) [29].

Physical interactions of ARMET

  • The removal of the positive or negative charges from these regions in HEXIM1 leads to its sequestration into the large complex and inhibition of transcription independently of the arginine-rich motif [30].
  • Moreover, the arginine-rich motif within it is essential for its binding to 7SK snRNA, P-TEFb, and inhibition of transcription [30].
  • These results provide evidence for the first time that arginine-rich signals are able to recognize different nuclear import receptors and transport the RASSF proteins into distinct sub-cellular compartments [31].
  • The driving force for arginine-rich selection appears to be the DNA-binding function of protamine P1 and an interaction with a protein kinase in the fertilized egg [32].
  • RNase S complex bearing arginine-rich peptide and anti-HIV activity [33].

Enzymatic interactions of ARMET

  • In addition, we speculate that lactoferrin may cleave arginine-rich sequences in a variety of microbial virulence proteins, contributing to its long-recognized antimicrobial properties [34].
  • The plasmin formed from plasminogen by the activators catalyzes the decomposition of the arginine-rich protamine substrate, yielding smaller polycationic fragments that are not sensed by the electrode [35].

Regulatory relationships of ARMET


Other interactions of ARMET


Analytical, diagnostic and therapeutic context of ARMET

  • These latter subjects received an L-amino acid-based diet that was arginine-rich or arginine-free each for 6 days prior to conduct, on day 7, of an 8-hr (first 3 hr, fast; final 5 hr, fed) primed continuous intravenous infusion protocol using L-[guanidino-13C]arginine, L-[5,5-2H2]citrulline, and L-[5,5,5-2H3]leucine, as tracers [42].
  • Western blots and mass spectrometry identified the HBcrAg as a 22-kDa precore protein (p22cr) containing the uncleaved signal peptide and lacking the arginine-rich domain that is involved in binding the RNA pregenome or the DNA genome [43].
  • Furthermore, using overlapping glutathione S-transferase (GST)-EB2 peptides, we have, by RNA electrophoretic mobility shift assays (REMSAs) and Northwestern blotting, located an RNA-binding motif in a 33-amino acid segment of EB2 that has structural features of the arginine-rich RNA-binding motifs (ARMs) also found in many RNA-binding proteins [44].
  • We have used affinity chromatography with immobilized transcription elongation factor SII to purify a protein complex that contains core RNA polymerase II (RNA Pol II), the general transcription initiation factors, and several splicing factors, including the U1, U2, and U4 small nuclear RNPs, the U2AF(65), and serine/arginine-rich proteins [45].
  • Complexes of the arginine-rich histone tetramer (H3)2(H4)2 with negatively supercoiled DNA: electron microscopy and chemical cross-linking [46].


  1. Mutations in the arginine-rich protein gene, in lung, breast, and prostate cancers, and in squamous cell carcinoma of the head and neck. Shridhar, R., Shridhar, V., Rivard, S., Siegfried, J.M., Pietraszkiewicz, H., Ensley, J., Pauley, R., Grignon, D., Sakr, W., Miller, O.J., Smith, D.I. Cancer Res. (1996) [Pubmed]
  2. Mutations in the arginine-rich protein gene (ARP) in pancreatic cancer. Shridhar, V., Rivard, S., Wang, X., Shridhar, R., Paisley, C., Mullins, C., Beirnat, L., Dugan, M., Sarkar, F., Miller, O.J., Vaitkevicius, V.K., Smith, D.I. Oncogene (1997) [Pubmed]
  3. A gene from human chromosomal band 3p21.1 encodes a highly conserved arginine-rich protein and is mutated in renal cell carcinomas. Shridhar, V., Rivard, S., Shridhar, R., Mullins, C., Bostick, L., Sakr, W., Grignon, D., Miller, O.J., Smith, D.I. Oncogene (1996) [Pubmed]
  4. Polymorphic variation of the ARP gene on 3p21 in Japanese esophageal cancer patients. Tanaka, H., Shimada, Y., Harada, H., Shinoda, M., Hatooka, S., Imamura, M., Ishizaki, K. Oncol. Rep. (2000) [Pubmed]
  5. HIV-1 structural gene expression requires binding of the Rev trans-activator to its RNA target sequence. Malim, M.H., Tiley, L.S., McCarn, D.F., Rusche, J.R., Hauber, J., Cullen, B.R. Cell (1990) [Pubmed]
  6. Activation mechanism of the MAP kinase ERK2 by dual phosphorylation. Canagarajah, B.J., Khokhlatchev, A., Cobb, M.H., Goldsmith, E.J. Cell (1997) [Pubmed]
  7. Arginine-rich histones do not exchange between human and mouse chromosomes in hybrid cells. Manser, T., Thacher, T., Rechsteiner, M. Cell (1980) [Pubmed]
  8. Defective high-density lipoprotein composition in patients on chronic hemodialysis. A possible mechanism for accelerated atherosclerosis. Rapoport, J., Aviram, M., Chaimovitz, C., Brook, J.G. N. Engl. J. Med. (1978) [Pubmed]
  9. Exonic splicing enhancers in fission yeast: functional conservation demonstrates an early evolutionary origin. Webb, C.J., Romfo, C.M., van Heeckeren, W.J., Wise, J.A. Genes Dev. (2005) [Pubmed]
  10. Developmental regulation of SR protein phosphorylation and activity. Sanford, J.R., Bruzik, J.P. Genes Dev. (1999) [Pubmed]
  11. The extracellular matrix on atherogenesis and diabetes-associated vascular disease. Camejo, G., Olsson, U., Hurt-Camejo, E., Baharamian, N., Bondjers, G. Atherosclerosis. Supplements. (2002) [Pubmed]
  12. Structural variety of arginine-rich RNA-binding peptides. Tan, R., Frankel, A.D. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  13. Gene activation by Varicella-zoster virus IE4 protein requires its dimerization and involves both the arginine-rich sequence, the central part, and the carboxyl-terminal cysteine-rich region. Baudoux, L., Defechereux, P., Rentier, B., Piette, J. J. Biol. Chem. (2000) [Pubmed]
  14. The Gly/Arg-rich (GAR) domain of Xenopus nucleolin facilitates in vitro nucleic acid binding and in vivo nucleolar localization. Heine, M.A., Rankin, M.L., DiMario, P.J. Mol. Biol. Cell (1993) [Pubmed]
  15. Cytokine induction by the hepatitis B virus capsid in macrophages is facilitated by membrane heparan sulfate and involves TLR2. Cooper, A., Tal, G., Lider, O., Shaul, Y. J. Immunol. (2005) [Pubmed]
  16. A novel splicing regulator shares a nuclear import pathway with SR proteins. Lai, M.C., Kuo, H.W., Chang, W.C., Tarn, W.Y. EMBO J. (2003) [Pubmed]
  17. Overexpression of the arginine-rich carboxy-terminal region of U1 snRNP 70K inhibits both splicing and nucleocytoplasmic transport of mRNA. Romac, J.M., Keene, J.D. Genes Dev. (1995) [Pubmed]
  18. Heterologous basic domain substitutions in the HIV-1 Tat protein reveal an arginine-rich motif required for transactivation. Subramanian, T., Govindarajan, R., Chinnadurai, G. EMBO J. (1991) [Pubmed]
  19. The ER repeat protein YT521-B localizes to a novel subnuclear compartment. Nayler, O., Hartmann, A.M., Stamm, S. J. Cell Biol. (2000) [Pubmed]
  20. Interactions of C-reactive protein with the complement system. II. C-reactive protein-mediated consumption of complement by poly-L-lysine polymers and other polycations. Siegel, J., Osmand, A.P., Wilson, M.F., Gewurz, H. J. Exp. Med. (1975) [Pubmed]
  21. Radioimmunoassay of human arginine-rich apolipoprotein, apoprotein E. Concentration in blood plasma and lipoproteins as affected by apoprotein E-3 deficiency. Havel, R.J., Kotite, L., Vigne, J.L., Kane, J.P., Tun, P., Phillips, N., Chen, G.C. J. Clin. Invest. (1980) [Pubmed]
  22. Low levels of eosinophil cationic proteins in patients with asthma. Venge, P., Zetterström, O., Dahl, R., Roxin, L.E., Olsson, I. Lancet (1977) [Pubmed]
  23. Primary structure of a human arginine-rich nuclear protein that colocalizes with spliceosome components. Chaudhary, N., McMahon, C., Blobel, G. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  24. Histone H3 disulfide dimers and nucleosome structure. Camerini-Otero, R.D., Felsenfeld, G. Proc. Natl. Acad. Sci. U.S.A. (1977) [Pubmed]
  25. Alterations in human high-density lipoproteins, with or without increased plasma-cholesterol, induced by diets high in cholesterol. Mahley, R.W., Innerarity, T.L., Bersot, T.P., Lipson, A., Margolis, S. Lancet (1978) [Pubmed]
  26. Cooperation of proto-signals for nuclear accumulation of estrogen and progesterone receptors. Ylikomi, T., Bocquel, M.T., Berry, M., Gronemeyer, H., Chambon, P. EMBO J. (1992) [Pubmed]
  27. Crystal structure of the CENP-B protein-DNA complex: the DNA-binding domains of CENP-B induce kinks in the CENP-B box DNA. Tanaka, Y., Nureki, O., Kurumizaka, H., Fukai, S., Kawaguchi, S., Ikuta, M., Iwahara, J., Okazaki, T., Yokoyama, S. EMBO J. (2001) [Pubmed]
  28. A yeast nucleolar protein related to mammalian fibrillarin is associated with small nucleolar RNA and is essential for viability. Schimmang, T., Tollervey, D., Kern, H., Frank, R., Hurt, E.C. EMBO J. (1989) [Pubmed]
  29. Type III hyperlipoproteinemia: paradoxical hypolipidemic response to estrogen. Kushwaha, R.S., Hazzard, W.R., Gagne, C., Chait, A., Albers, J.J. Ann. Intern. Med. (1977) [Pubmed]
  30. Interplay between 7SK snRNA and oppositely charged regions in HEXIM1 direct the inhibition of P-TEFb. Barboric, M., Kohoutek, J., Price, J.P., Blazek, D., Price, D.H., Peterlin, B.M. EMBO J. (2005) [Pubmed]
  31. Nuclear Transport of Ras-associated Tumor Suppressor Proteins: Different Transport Receptor Binding Specificities for Arginine-rich Nuclear Targeting Signals. Kumari, G., Singhal, P.K., Rao, M.R., Mahalingam, S. J. Mol. Biol. (2007) [Pubmed]
  32. An unusual form of purifying selection in a sperm protein. Rooney, A.P., Zhang, J., Nei, M. Mol. Biol. Evol. (2000) [Pubmed]
  33. RNase S complex bearing arginine-rich peptide and anti-HIV activity. Futaki, S., Nakase, I., Suzuki, T., Nameki, D., Kodama, E., Matsuoka, M., Sugiura, Y. J. Mol. Recognit. (2005) [Pubmed]
  34. Human milk lactoferrin is a serine protease that cleaves Haemophilus surface proteins at arginine-rich sites. Hendrixson, D.R., Qiu, J., Shewry, S.C., Fink, D.L., Petty, S., Baker, E.N., Plaut, A.G., St Geme, J.W. Mol. Microbiol. (2003) [Pubmed]
  35. Electrochemical assay of plasminogen activators in plasma using polyion-sensitive membrane electrode detection. Chang, L.C., Meyerhoff, M.E., Yang, V.C. Anal. Biochem. (1999) [Pubmed]
  36. The RNA-splicing factor PSF/p54 controls DNA-topoisomerase I activity by a direct interaction. Straub, T., Grue, P., Uhse, A., Lisby, M., Knudsen, B.R., Tange, T.O., Westergaard, O., Boege, F. J. Biol. Chem. (1998) [Pubmed]
  37. A human immunodeficiency virus type 1 Tat-like arginine-rich RNA-binding domain is essential for HEXIM1 to inhibit RNA polymerase II transcription through 7SK snRNA-mediated inactivation of P-TEFb. Yik, J.H., Chen, R., Pezda, A.C., Samford, C.S., Zhou, Q. Mol. Cell. Biol. (2004) [Pubmed]
  38. Arginine-rich anti-vascular endothelial growth factor peptides inhibit tumor growth and metastasis by blocking angiogenesis. Bae, D.G., Gho, Y.S., Yoon, W.H., Chae, C.B. J. Biol. Chem. (2000) [Pubmed]
  39. Resistance to mitomycin C requires direct interaction between the Fanconi anemia proteins FANCA and FANCG in the nucleus through an arginine-rich domain. Kruyt, F.A., Abou-Zahr, F., Mok, H., Youssoufian, H. J. Biol. Chem. (1999) [Pubmed]
  40. Two arginine rich domains in the p14ARF tumour suppressor mediate nucleolar localization. Rizos, H., Darmanian, A.P., Mann, G.J., Kefford, R.F. Oncogene (2000) [Pubmed]
  41. Arginine-rich cationic polypeptides amplify lipopolysaccharide-induced monocyte activation. Bosshart, H., Heinzelmann, M. Infect. Immun. (2002) [Pubmed]
  42. Plasma arginine and citrulline kinetics in adults given adequate and arginine-free diets. Castillo, L., Chapman, T.E., Sanchez, M., Yu, Y.M., Burke, J.F., Ajami, A.M., Vogt, J., Young, V.R. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  43. Hepatitis B virus DNA-negative dane particles lack core protein but contain a 22-kDa precore protein without C-terminal arginine-rich domain. Kimura, T., Ohno, N., Terada, N., Rokuhara, A., Matsumoto, A., Yagi, S., Tanaka, E., Kiyosawa, K., Ohno, S., Maki, N. J. Biol. Chem. (2005) [Pubmed]
  44. A region of the Epstein-Barr virus (EBV) mRNA export factor EB2 containing an arginine-rich motif mediates direct binding to RNA. Hiriart, E., Bardouillet, L., Manet, E., Gruffat, H., Penin, F., Montserret, R., Farjot, G., Sergeant, A. J. Biol. Chem. (2003) [Pubmed]
  45. A human RNA polymerase II-containing complex associated with factors necessary for spliceosome assembly. Robert, F., Blanchette, M., Maes, O., Chabot, B., Coulombe, B. J. Biol. Chem. (2002) [Pubmed]
  46. Complexes of the arginine-rich histone tetramer (H3)2(H4)2 with negatively supercoiled DNA: electron microscopy and chemical cross-linking. Thomas, J.O., Oudet, P. Nucleic Acids Res. (1979) [Pubmed]
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