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Gene Review

YME1L1  -  YME1-like 1 ATPase

Homo sapiens

Synonyms: ATP-dependent metalloprotease FtsH1, ATP-dependent zinc metalloprotease YME1L1, FTSH, FTSH1, MEG4, ...
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Disease relevance of YME1L1

  • YME1L1 may represent a candidate gene for other forms of hereditary spastic paraplegia and possibly for other neurodegenerative disorders [1].
  • CONCLUSIONS: PAMP is an effective treatment for advanced ovarian cancer with a 67% response rate after 4 cycles [2].
  • Treatments that modify AM expression, such as exposure to hypoxia, were shown to change the B/A ratio and the relative secretion of AM and PAMP, indicating that the splicing mechanism for AM can be modulated and is physiologically relevant [3].
  • Toxicity of PAMP was acceptable with 10% of WHO grade 4 hematologic toxicity [2].
  • Lipopolysaccharides (LPS) derived from Gram-negative bacteria are representative of typical PAMP molecules and have been reported to induce defense-related responses, including the suppression of the hypersensitive response, the expression of defense genes and systemic resistance in plants [4].

High impact information on YME1L1

  • We found that human microvascular endothelial cells express PAMP receptors and respond to exogenous addition of PAMP by increasing migration and cord formation [5].
  • CONCLUSIONS : AM production was stimulated by aldosterone in cultured human VSMC without an increase in PAMP secretion, suggesting a possible role of AM in modulating vascular remodeling by aldosterone [6].
  • Since aldosterone has been shown to be involved in vascular remodeling, we examined the effects of aldosterone on AM and PAMP secretion and preproAM gene expression in human aortic vascular smooth muscle cells (VSMC) [6].
  • OBJECTIVE : Both adrenomedullin (AM) and pro-adrenomedullin N-terminal 20 peptide (PAMP), processed from the same precursor of prepro-adrenomedullin (preproAM), have differential biological properties; AM dilates blood vessels and presumably affects the vascular remodeling, while PAMP inhibits catecholamine secretion [6].
  • In the PC-310 and PC-295 androgen-dependent models, PAMP or PAM NE differentiation was induced after castration in different ways, being higher in PC-310, which might explain its long-term survival after androgen deprivation [7].

Chemical compound and disease context of YME1L1

  • BACKGROUND: The primary aim was to induce a high number of pCR in early (FIGO IC, IIB + C) - and advanced (FIGO III-IV) - stage ovarian cancer with a surgery plus 4 cycles of cisplatin and melphalan (PAMP) regimen [2].
  • Between April 1981 and June 1985, 195 patients with ovarian cancer, International Federation of Gynecology and Obstetrics (FIGO) Stages IIB, IIC, III, and IV, entered a trial that consisted of surgery and chemotherapy with cisplatin (P) and melphalan (PAM) with or without hexamethylmelamine (HexaPAMP or PAMP regimens) every 4 weeks for 6 cycles [8].
  • First that adrenomedullin and PAMP are regulated by different mechanisms in vascular and adrenal cells and second, that LPS is able to directly stimulate cortisol secretion, with implications for the physiological response to septic shock [9].

Biological context of YME1L1

  • By screening the expressed sequence tag database, we identified and characterized a novel human gene, YME1L1 (YME1L1-like1, HGMW-approved symbol) [1].
  • Transfection of both HEK-293EBNA and yeast cells with a green fluorescent protein-tagged YME1L cDNA confirmed mitochondrial targeting [10].
  • When expressed in a yme1 disruptant yeast strain, YME1L restored growth on glycerol at 37 degrees C. We propose that YME1L plays a phylogenetically conserved role in mitochondrial protein metabolism and could be involved in mitochondrial pathologies [10].
  • Aldosterone increased preproAM gene expression in the cultured VSMC in a dose-dependent fashion following incubation for 48 h, with a concomitant increase in AM secretion from the cells, but PAMP secretion remained unchanged [6].
  • Thoracic electrical impedance (TI), heart rate (HR), central venous (CVP), pulmonary artery mean (PAMP), pulmonary wedge (PWP) and mean arterial (MAP) pressure as well as fourteen arterial and venous blood gas variables were followed [11].

Anatomical context of YME1L1

  • Form B was found in cells that express PAMP but not AM. mRNA expression in a variety of cell lines was investigated by ribonuclease protection assay and form B was found in significant amounts in two of them [3].
  • The ATP-dependent metalloprotease FtsH is bound to the thylakoid membrane, facing the stroma [12].
  • The only study of PAMP in man showed that its skeletal muscle vasodilator potency, when infused into the brachial artery of healthy volunteers, was less than one hundredth that of AM, and it was without effect on skin blood flow [13].
  • There is evidence to suggest that the cells of the vascular endothelium secrete factors, including endothelin-1, nitric oxide, adrenomedullin and PAMP which have a role in regulating adrenal function [14].
  • Effects of two saponins extracted from the polygonatum Zanlanscianense pamp on the human leukemia (HL-60) cells [15].

Associations of YME1L1 with chemical compounds

  • Although the correlation of either marker to tumor grade, clinical progression or disease prognosis did not reach statistical significance, PAMP- or PAM-immunoreactive cells were induced after androgen-blockade therapy [7].
  • CGRP, ADM, and PAMP produced concentration-dependent vasodilator responses in arteries preconstricted with the thromboxane mimic U-46619 [16].
  • While checking anticoagulant activities in crude fractions from Wakan-Yakus (traditional herbal drugs), we detected antithrombin activity in the polysaccharide fraction of the leaves of Artemisia princeps Pamp [17].
  • The preferred conformation of PAMP was determined in a helix-inducing trifluoroethanol and water (TFE/H2O) solution, and in a membrane-mimetic sodium dodecylsulfate-d25 (SDS) micellar solution [18].
  • Decreases in systemic arterial pressure in response to human proadrenomedullin NH2-terminal 20 peptide (hPAMP), a truncated analog, hPAMP(12-20), and human adrenomedullin (hADM) were compared in the rat and cat [19].

Other interactions of YME1L1

  • Identification and characterization of YME1L1, a novel paraplegin-related gene [1].
  • MRS2L, YME1L and MIPEP have been sequenced in three patients with a combined defect of complexes III and IV [20].

Analytical, diagnostic and therapeutic context of YME1L1

  • Expression and immunofluorescence studies revealed that YME1L1 and paraplegin share a similar expression pattern and the same subcellular localization in the mitochondrial compartment [1].
  • We studied expression of PAMP and PAM in normal prostate and prostatic tumors (clinical specimens and human xenograft models) with or without prior androgen-deprivation therapy and found a wide distribution of both molecules in NE subpopulations of all kinds [7].
  • METHODS : AM and PAMP secreted from human VSMC incubated with aldosterone were measured by radioimmunoassay, and preproAM gene expression was evaluated by quantitative polymerase chain reaction [6].
  • The treatment of ovarian cancer by a multimodality approach: remission induction with chemotherapy--hexa PAMP and PAMP regimens--followed by whole-abdominal radiation [21].
  • After placebo and after 2 and 6 hours with 40 mg ISDN, the heart rate (HR), cardiac index (CI), pressure values in the pulmonary artery (PASP, PAMP, PAEDP) and in the aorta (AoSP, AoMP, AoEDP) and systemic vascular resistance (SVR) were measured at rest and during bicycle ergometry [22].


  1. Identification and characterization of YME1L1, a novel paraplegin-related gene. Coppola, M., Pizzigoni, A., Banfi, S., Bassi, M.T., Casari, G., Incerti, B. Genomics (2000) [Pubmed]
  2. Treatment of ovarian cancer with surgery, short-course chemotherapy and whole abdominal radiation. Buser, K., Bacchi, M., Goldhirsch, A., Greiner, R., Diener, P., Sessa, C., Jungi, W.F., Forni, M., Leyvraz, S., Engeler, V. Ann. Oncol. (1996) [Pubmed]
  3. Alternative splicing of the proadrenomedullin gene results in differential expression of gene products. Martínez, A., Hodge, D.L., Garayoa, M., Young, H.A., Cuttitta, F. J. Mol. Endocrinol. (2001) [Pubmed]
  4. Bacterial lipopolysaccharides induce defense responses associated with programmed cell death in rice cells. Desaki, Y., Miya, A., Venkatesh, B., Tsuyumu, S., Yamane, H., Kaku, H., Minami, E., Shibuya, N. Plant Cell Physiol. (2006) [Pubmed]
  5. Proadrenomedullin NH2-terminal 20 peptide is a potent angiogenic factor, and its inhibition results in reduction of tumor growth. Martínez, A., Zudaire, E., Portal-Núñez, S., Guédez, L., Libutti, S.K., Stetler-Stevenson, W.G., Cuttitta, F. Cancer Res. (2004) [Pubmed]
  6. Aldosterone augments adrenomedullin production without stimulating pro-adrenomedullin N-terminal 20 peptide secretion in vascular smooth muscle cells. Uemura, T., Kato, J., Kuwasako, K., Kitamura, K., Kangawa, K., Eto, T. J. Hypertens. (2002) [Pubmed]
  7. Peptidylglycine alpha-amidating monooxygenase- and proadrenomedullin-derived peptide-associated neuroendocrine differentiation are induced by androgen deprivation in the neoplastic prostate. Jiménez, N., Jongsma, J., Calvo, A., van der Kwast, T.H., Treston, A.M., Cuttitta, F., Schröder, F.H., Montuenga, L.M., van Steenbrugge, G.J. Int. J. Cancer (2001) [Pubmed]
  8. Treatment of advanced ovarian cancer with surgery, chemotherapy, and consolidation of response by whole-abdominal radiotherapy. Goldhirsch, A., Greiner, R., Dreher, E., Sessa, C., Krauer, F., Forni, M., Jungi, F.W., Brunner, K.W., Veraguth, P., Engeler, V. Cancer (1988) [Pubmed]
  9. Bacterial lipopolysaccharide directly stimulates cortisol secretion in human adrenal cells. Vakharia, K., Renshaw, D., Hinson, J.P. Endocr. Res. (2002) [Pubmed]
  10. The human homologue of the yeast mitochondrial AAA metalloprotease Yme1p complements a yeast yme1 disruptant. Shah, Z.H., Hakkaart, G.A., Arku, B., de Jong, L., van der Spek, H., Grivell, L.A., Jacobs, H.T. FEBS Lett. (2000) [Pubmed]
  11. Thoracic electrical impedance and fluid balance during aortic surgery. Jónsson, F., Madsen, P., Jørgensen, L.G., Lunding, M., Secher, N.H. Acta anaesthesiologica Scandinavica. (1995) [Pubmed]
  12. Chloroplast proteases: possible regulators of gene expression? Adam, Z. Biochimie (2000) [Pubmed]
  13. Bioactivity of adrenomedullin and proadrenomedullin N-terminal 20 peptide in man. Nicholls, M.G., Lainchbury, J.G., Lewis, L.K., McGregor, D.O., Richards, A.M., Troughton, R.W., Yandle, T.G. Peptides (2001) [Pubmed]
  14. The role of endothelial cell products in the regulation of adrenocortical function: actions of endothelin, nitric oxide, adrenomedullin and PAMP. Hinson, J.P., Kapas, S. Horm. Metab. Res. (1998) [Pubmed]
  15. Effects of two saponins extracted from the polygonatum Zanlanscianense pamp on the human leukemia (HL-60) cells. Wang, Z., Zhou, J., Ju, Y., Zhang, H., Liu, M., Li, X. Biol. Pharm. Bull. (2001) [Pubmed]
  16. Responses to human CGRP, ADM, and PAMP in human thymic arteries. Champion, H.C., Bivalacqua, T.J., Pierce, R.L., Murphy, W.A., Coy, D.H., Hyman, A.L., Kadowitz, P.J. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2003) [Pubmed]
  17. Selective activation of heparin cofactor II by a sulfated polysaccharide isolated from the leaves of Artemisia princeps. Hayakawa, Y., Hayashi, T., Hayashi, T., Niiya, K., Sakuragawa, N. Blood Coagul. Fibrinolysis (1995) [Pubmed]
  18. NMR conformational analysis of proadrenomedullin N-terminal 20 peptide, a proangiogenic factor involved in tumor growth. Lucyk, S., Taha, H., Yamamoto, H., Miskolzie, M., Kotovych, G. Biopolymers (2006) [Pubmed]
  19. Proadrenomedullin NH2-terminal peptide (PAMP)(12-20) has vasodepressor activity in the rat and cat. Fry, R.C., Champion, H.C., Lawrence, T.C., Murphy, W.A., Coy, D.H., Kadowitz, P.J. Life Sci. (1997) [Pubmed]
  20. Mutation detection in four candidate genes (OXA1L, MRS2L, YME1L and MIPEP) for combined deficiencies in the oxidative phosphorylation system. Coenen, M.J., Smeitink, J.A., Smeets, R., Trijbels, F.J., van den Heuvel, L.P. J. Inherit. Metab. Dis. (2005) [Pubmed]
  21. The treatment of ovarian cancer by a multimodality approach: remission induction with chemotherapy--hexa PAMP and PAMP regimens--followed by whole-abdominal radiation. Goldhirsch, A., Greiner, R., Dreher, E., Locher, G., Davis, B.W., Reinhard, J.P., Joss, R., Brunner, K.W. Onkologie. (1985) [Pubmed]
  22. Effect of slow-release ISDN on cardiac function in patients with coronary heart disease during bicycle ergometry. Pech, H.J., Parsi, R.A. Cor et vasa. (1986) [Pubmed]
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