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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/01/30 09:41:57」(JST)
[Wiki en表示]
| Inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma |
Rendering based on PDB 2JVX. |
| Available structures |
| PDB |
Ortholog search: PDBe, RCSB |
| List of PDB id codes |
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2JVX, 2JVY, 3BRT, 3BRV, 3CL3, 3FX0
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| Identifiers |
| Symbols |
IKBKG; AMCBX1; FIP-3; FIP3; Fip3p; IKK-gamma; IP; IP1; IP2; IPD2; NEMO; ZC2HC9 |
| External IDs |
OMIM: 300248 MGI: 1338074 HomoloGene: 2698 ChEMBL: 4967 GeneCards: IKBKG Gene |
| Gene Ontology |
| Molecular function |
• signal transducer activity
• protein binding
• protein domain specific binding
• metal ion binding
• protein heterodimerization activity
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| Cellular component |
• intracellular
• nucleus
• cytoplasm
• cytosol
• IkappaB kinase complex
• cytoplasmic part
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| Biological process |
• activation of MAPK activity
• B cell homeostasis
• toll-like receptor signaling pathway
• MyD88-dependent toll-like receptor signaling pathway
• MyD88-independent toll-like receptor signaling pathway
• transcription, DNA-dependent
• induction of apoptosis
• inflammatory response
• immune response
• response to DNA damage stimulus
• I-kappaB kinase/NF-kappaB cascade
• activation of NF-kappaB-inducing kinase activity
• JNK cascade
• response to virus
• virus-host interaction
• positive regulation of type I interferon production
• toll-like receptor 2 signaling pathway
• toll-like receptor 3 signaling pathway
• toll-like receptor 4 signaling pathway
• toll-like receptor 5 signaling pathway
• toll-like receptor 9 signaling pathway
• toll-like receptor 10 signaling pathway
• TRIF-dependent toll-like receptor signaling pathway
• nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
• toll-like receptor TLR1:TLR2 signaling pathway
• toll-like receptor TLR6:TLR2 signaling pathway
• positive regulation of I-kappaB kinase/NF-kappaB cascade
• innate immune response
• T cell receptor signaling pathway
• positive regulation of NF-kappaB transcription factor activity
• stress-activated MAPK cascade
• nucleotide-binding oligomerization domain containing signaling pathway
|
| Sources: Amigo / QuickGO |
|
| RNA expression pattern |
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| More reference expression data |
| Orthologs |
| Species |
Human |
Mouse |
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| Entrez |
8517 |
16151 |
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| Ensembl |
ENSG00000073009 |
ENSMUSG00000004221 |
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| UniProt |
Q9Y6K9 |
O88522 |
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| RefSeq (mRNA) |
NM_001099856 |
NM_001136067 |
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| RefSeq (protein) |
NP_001093326 |
NP_001129539 |
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| Location (UCSC) |
Chr HG1497_PATCH:
153.75 – 153.77 Mb |
Chr X:
74.39 – 74.45 Mb |
|
| PubMed search |
[1] |
[2] |
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NF-kappa-B essential modulator (NEMO) also known as inhibitor of nuclear factor kappa-B kinase subunit gamma (IKK-γ) is a protein that in humans is encoded by the IKBKG gene. NEMO is a subunit of the IκB kinase complex that activates NF-κB.[1] The human gene for IKBKG is located on chromosome Xq28.[2] Multiple transcript variants encoding different isoforms have been found for this gene.
Contents
- 1 Function
- 2 Clinical significance
- 3 Interactions
- 4 References
- 5 Further reading
- 6 External links
Function[edit]
Main article: IκB kinase
NEMO (IKK-γ) is the regulatory subunit of the inhibitor of IκB kinase (IKK) complex, which activates NF-κB resulting in activation of genes involved in inflammation, immunity, cell survival, and other pathways.
Clinical significance[edit]
Mutations in the IKBKG gene results in incontinentia pigmenti,[3] hypohidrotic ectodermal dysplasia,[4] and several other types of immunodeficiencies.
Incontinentia Pigmenti (IP) is an X-linked dominant disease caused by a mutation in the IKBKG gene. Since IKBKG helps activate NF-κB, which protects cells against TNF-alpha induced apoptosis, a lack of IKBKG (and hence a lack of active NF-κB) makes cells more prone to apoptosis.
Interactions[edit]
IKBKG has been shown to interact with:
- BCL10,[5]
- CDC37,[6][7]
- CHUK,[7][8][9][10]
- IKK2,[7][9][10][11][12]
- IRAK1,[13][14]
- NCOA3,[12]
- PPM1B,[15]
- TANK.[11]
- TNFAIP3,[16]
- TRAF3IP2,[17][18] and
- TRAF6.[14][19]
References[edit]
- ^ Rothwarf DM, Zandi E, Natoli G, Karin M (1998). "IKK-gamma is an essential regulatory subunit of the IkappaB kinase complex". Nature 395 (6699): 297–300. doi:10.1038/26261. PMID 9751060.
- ^ Jin DY, Jeang KT (1999). "Isolation of full-length cDNA and chromosomal localization of human NF-kappaB modulator NEMO to Xq28". J. Biomed. Sci. 6 (2): 115–20. doi:10.1159/000025378. PMID 10087442.
- ^ Aradhya S, Woffendin H, Jakins T, Bardaro T, Esposito T, Smahi A, Shaw C, Levy M, Munnich A, D'Urso M, Lewis RA, Kenwrick S, Nelson DL (September 2001). "A recurrent deletion in the ubiquitously expressed NEMO (IKK-gamma) gene accounts for the vast majority of incontinentia pigmenti mutations". Hum. Mol. Genet. 10 (19): 2171–9. doi:10.1093/hmg/10.19.2171. PMID 11590134.
- ^ Zonana J, Elder ME, Schneider LC, Orlow SJ, Moss C, Golabi M, Shapira SK, Farndon PA, Wara DW, Emmal SA, Ferguson BM (December 2000). "A Novel X-Linked Disorder of Immune Deficiency and Hypohidrotic Ectodermal Dysplasia Is Allelic to Incontinentia Pigmenti and Due to Mutations in IKK-gamma (NEMO)". Am. J. Hum. Genet. 67 (6): 1555–62. doi:10.1086/316914. PMC 1287930. PMID 11047757.
- ^ Wu, Chuan-Jin; Ashwell Jonathan D (February 2008). "NEMO recognition of ubiquitinated Bcl10 is required for T cell receptor-mediated NF-κB activation". Proc. Natl. Acad. Sci. U.S.A. (United States) 105 (8): 3023–8. doi:10.1073/pnas.0712313105. PMC 2268578. PMID 18287044.
- ^ Bouwmeester, Tewis; Bauch Angela, Ruffner Heinz, Angrand Pierre-Olivier, Bergamini Giovanna, Croughton Karen, Cruciat Cristina, Eberhard Dirk, Gagneur Julien, Ghidelli Sonja, Hopf Carsten, Huhse Bettina, Mangano Raffaella, Michon Anne-Marie, Schirle Markus, Schlegl Judith, Schwab Markus, Stein Martin A, Bauer Andreas, Casari Georg, Drewes Gerard, Gavin Anne-Claude, Jackson David B, Joberty Gerard, Neubauer Gitte, Rick Jens, Kuster Bernhard, Superti-Furga Giulio (February 2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nat. Cell Biol. (England) 6 (2): 97–105. doi:10.1038/ncb1086. ISSN 1465-7392. PMID 14743216.
- ^ a b c Chen, Guoqing; Cao Ping, Goeddel David V (February 2002). "TNF-induced recruitment and activation of the IKK complex require Cdc37 and Hsp90". Mol. Cell (United States) 9 (2): 401–10. doi:10.1016/S1097-2765(02)00450-1. ISSN 1097-2765. PMID 11864612.
- ^ Agou, Fabrice; Ye Fei, Goffinont Stéphane, Courtois Gilles, Yamaoka Shoji, Israël Alain, Véron Michel (May 2002). "NEMO trimerizes through its coiled-coil C-terminal domain". J. Biol. Chem. (United States) 277 (20): 17464–75. doi:10.1074/jbc.M201964200. ISSN 0021-9258. PMID 11877453.
- ^ a b Deng, L; Wang C, Spencer E, Yang L, Braun A, You J, Slaughter C, Pickart C, Chen Z J (October 2000). "Activation of the IkappaB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain". Cell (UNITED STATES) 103 (2): 351–61. doi:10.1016/S0092-8674(00)00126-4. ISSN 0092-8674. PMID 11057907.
- ^ a b Shifera, Amde Selassie; Horwitz Marshall S (March 2008). "Mutations in the zinc finger domain of IKK gamma block the activation of NF-kappa B and the induction of IL-2 in stimulated T lymphocytes". Mol. Immunol. (England) 45 (6): 1633–45. doi:10.1016/j.molimm.2007.09.036. ISSN 0161-5890. PMID 18207244.
- ^ a b Chariot, Alain; Leonardi Antonio, Muller Jurgen, Bonif Marianne, Brown Keith, Siebenlist Ulrich (October 2002). "Association of the adaptor TANK with the I kappa B kinase (IKK) regulator NEMO connects IKK complexes with IKK epsilon and TBK1 kinases". J. Biol. Chem. (United States) 277 (40): 37029–36. doi:10.1074/jbc.M205069200. ISSN 0021-9258. PMID 12133833.
- ^ a b Wu, Ray-Chang; Qin Jun, Hashimoto Yoshihiro, Wong Jiemin, Xu Jianming, Tsai Sophia Y, Tsai Ming-Jer, O'Malley Bert W (May 2002). "Regulation of SRC-3 (pCIP/ACTR/AIB-1/RAC-3/TRAM-1) Coactivator Activity by IκB Kinase". Mol. Cell. Biol. (United States) 22 (10): 3549–61. doi:10.1128/MCB.22.10.3549-3561.2002. ISSN 0270-7306. PMC 133790. PMID 11971985.
- ^ Conze, Dietrich B; Wu Chuan-Jin, Thomas James A, Landstrom Allison, Ashwell Jonathan D (May 2008). "Lys63-Linked Polyubiquitination of IRAK-1 Is Required for Interleukin-1 Receptor- and Toll-Like Receptor-Mediated NF-κB Activation". Mol. Cell. Biol. (United States) 28 (10): 3538–47. doi:10.1128/MCB.02098-07. PMC 2423148. PMID 18347055.
- ^ a b Windheim, Mark; Stafford Margaret, Peggie Mark, Cohen Philip (March 2008). "Interleukin-1 (IL-1) Induces the Lys63-Linked Polyubiquitination of IL-1 Receptor-Associated Kinase 1 To Facilitate NEMO Binding and the Activation of IκBα Kinase". Mol. Cell. Biol. (United States) 28 (5): 1783–91. doi:10.1128/MCB.02380-06. PMC 2258775. PMID 18180283.
- ^ Prajapati, Shashi; Verma Udit, Yamamoto Yumi, Kwak Youn Tae, Gaynor Richard B (January 2004). "Protein phosphatase 2Cbeta association with the IkappaB kinase complex is involved in regulating NF-kappaB activity". J. Biol. Chem. (United States) 279 (3): 1739–46. doi:10.1074/jbc.M306273200. ISSN 0021-9258. PMID 14585847.
- ^ Zhang, S Q; Kovalenko A, Cantarella G, Wallach D (March 2000). "Recruitment of the IKK signalosome to the p55 TNF receptor: RIP and A20 bind to NEMO (IKKgamma) upon receptor stimulation". Immunity (UNITED STATES) 12 (3): 301–11. doi:10.1016/S1074-7613(00)80183-1. ISSN 1074-7613. PMID 10755617.
- ^ Leonardi, A; Chariot A, Claudio E, Cunningham K, Siebenlist U (September 2000). "CIKS, a connection to IκB kinase and stress-activated protein kinase". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 97 (19): 10494–9. doi:10.1073/pnas.190245697. ISSN 0027-8424. PMC 27052. PMID 10962033.
- ^ Li, X; Commane M, Nie H, Hua X, Chatterjee-Kishore M, Wald D, Haag M, Stark G R (September 2000). "Act1, an NF-κB-activating protein". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 97 (19): 10489–93. doi:10.1073/pnas.160265197. ISSN 0027-8424. PMC 27051. PMID 10962024.
- ^ Lamothe, Betty; Campos Alejandro D, Webster William K, Gopinathan Ambily, Hur Lana, Darnay Bryant G (September 2008). "The RING Domain and First Zinc Finger of TRAF6 Coordinate Signaling by Interleukin-1, Lipopolysaccharide, and RANKL". J. Biol. Chem. (United States) 283 (36): 24871–80. doi:10.1074/jbc.M802749200. ISSN 0021-9258. PMC 2529010. PMID 18617513.
Further reading[edit]
- Rothwarf DM, Zandi E, Natoli G, Karin M (1998). "IKK-gamma is an essential regulatory subunit of the IkappaB kinase complex". Nature 395 (6699): 297–300. doi:10.1038/26261. PMID 9751060.
- Mercurio F, Murray BW, Shevchenko A, et al. (1999). "IκB Kinase (IKK)-Associated Protein 1, a Common Component of the Heterogeneous IKK Complex". Mol. Cell. Biol. 19 (2): 1526–38. PMC 116081. PMID 9891086.
- Li Y, Kang J, Friedman J, et al. (1999). "Identification of a cell protein (FIP-3) as a modulator of NF-κB activity and as a target of an adenovirus inhibitor of tumor necrosis factor α-induced apoptosis". Proc. Natl. Acad. Sci. U.S.A. 96 (3): 1042–7. doi:10.1073/pnas.96.3.1042. PMC 15347. PMID 9927690.
- Jin DY, Jeang KT (1999). "Isolation of full-length cDNA and chromosomal localization of human NF-kappaB modulator NEMO to Xq28". J. Biomed. Sci. 6 (2): 115–20. doi:10.1159/000025378. PMID 10087442.
- Jin DY, Giordano V, Kibler KV, et al. (1999). "Role of adapter function in oncoprotein-mediated activation of NF-kappaB. Human T-cell leukemia virus type I Tax interacts directly with IkappaB kinase gamma". J. Biol. Chem. 274 (25): 17402–5. doi:10.1074/jbc.274.25.17402. PMID 10364167.
- Zhang SQ, Kovalenko A, Cantarella G, Wallach D (2000). "Recruitment of the IKK signalosome to the p55 TNF receptor: RIP and A20 bind to NEMO (IKKgamma) upon receptor stimulation". Immunity 12 (3): 301–11. doi:10.1016/S1074-7613(00)80183-1. PMID 10755617.
- Smahi A, Courtois G, Vabres P, et al. (2000). "Genomic rearrangement in NEMO impairs NF-kappaB activation and is a cause of incontinentia pigmenti. The International Incontinentia Pigmenti (IP) Consortium". Nature 405 (6785): 466–72. doi:10.1038/35013114. PMID 10839543.
- Inohara N, Koseki T, Lin J, et al. (2000). "An induced proximity model for NF-kappa B activation in the Nod1/RICK and RIP signaling pathways". J. Biol. Chem. 275 (36): 27823–31. doi:10.1074/jbc.M003415200. PMID 10880512.
- Ye Z, Connor JR (2000). "cDNA cloning by amplification of circularized first strand cDNAs reveals non-IRE-regulated iron-responsive mRNAs". Biochem. Biophys. Res. Commun. 275 (1): 223–7. doi:10.1006/bbrc.2000.3282. PMID 10944468.
- Li X, Commane M, Nie H, et al. (2000). "Act1, an NF-κB-activating protein". Proc. Natl. Acad. Sci. U.S.A. 97 (19): 10489–93. doi:10.1073/pnas.160265197. PMC 27051. PMID 10962024.
- Leonardi A, Chariot A, Claudio E, et al. (2000). "CIKS, a connection to IκB kinase and stress-activated protein kinase". Proc. Natl. Acad. Sci. U.S.A. 97 (19): 10494–9. doi:10.1073/pnas.190245697. PMC 27052. PMID 10962033.
- May MJ, D'Acquisto F, Madge LA, et al. (2000). "Selective inhibition of NF-kappaB activation by a peptide that blocks the interaction of NEMO with the IkappaB kinase complex". Science 289 (5484): 1550–4. doi:10.1126/science.289.5484.1550. PMID 10968790.
- Zonana J, Elder ME, Schneider LC, et al. (2001). "A Novel X-Linked Disorder of Immune Deficiency and Hypohidrotic Ectodermal Dysplasia Is Allelic to Incontinentia Pigmenti and Due to Mutations in IKK-gamma (NEMO)". Am. J. Hum. Genet. 67 (6): 1555–62. doi:10.1086/316914. PMC 1287930. PMID 11047757.
- Xiao G, Sun SC (2000). "Activation of IKKalpha and IKKbeta through their fusion with HTLV-I tax protein". Oncogene 19 (45): 5198–203. doi:10.1038/sj.onc.1203894. PMID 11064457.
- Li XH, Fang X, Gaynor RB (2001). "Role of IKKgamma/nemo in assembly of the Ikappa B kinase complex". J. Biol. Chem. 276 (6): 4494–500. doi:10.1074/jbc.M008353200. PMID 11080499.
- Poyet JL, Srinivasula SM, Alnemri ES (2001). "vCLAP, a caspase-recruitment domain-containing protein of equine Herpesvirus-2, persistently activates the Ikappa B kinases through oligomerization of IKKgamma". J. Biol. Chem. 276 (5): 3183–7. doi:10.1074/jbc.C000792200. PMID 11113112.
- Jain A, Ma CA, Liu S, et al. (2001). "Specific missense mutations in NEMO result in hyper-IgM syndrome with hypohydrotic ectodermal dysplasia". Nat. Immunol. 2 (3): 223–8. doi:10.1038/85277. PMID 11224521.
- Döffinger R, Smahi A, Bessia C, et al. (2001). "X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF-kappaB signaling". Nat. Genet. 27 (3): 277–85. doi:10.1038/85837. PMID 11242109.
- Simpson JC, Wellenreuther R, Poustka A, et al. (2001). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing". EMBO Rep. 1 (3): 287–92. doi:10.1093/embo-reports/kvd058. PMC 1083732. PMID 11256614.
- Galgóczy P, Rosenthal A, Platzer M (2001). "Human-mouse comparative sequence analysis of the NEMO gene reveals an alternative promoter within the neighboring G6PD gene". Gene 271 (1): 93–8. doi:10.1016/S0378-1119(01)00492-9. PMID 11410370.
External links[edit]
- IKBKG protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
- GeneReviews/NIH/NCBI/UW entry on Incontinentia Pigmenti
- OMIM IKBKG
- GeneReviews/NCBI/NIH/UW entry on Anophthalmia / Microphthalmia Overview
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Kinases: Serine/threonine-specific protein kinases (EC 2.7.11-12)
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Serine/threonine-specific protein kinases (EC 2.7.11.1-EC 2.7.11.20)
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Serine/threonine-specific protein kinases (EC 2.7.11.21-EC 2.7.11.30)
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| Polo kinase (EC 2.7.11.21) |
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| Cyclin-dependent kinase (EC 2.7.11.22) |
- CDK1
- CDK2
- CDKL2
- CDK3
- CDK4
- CDK5
- CDKL5
- CDK6
- CDK7
- CDK8
- CDK9
- CDK10
- CDC2L5
- CRKRS
- PCTK1
- PCTK2
- PCTK3
- PFTK1
- CDC2L1
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| (RNA-polymerase)-subunit kinase (EC 2.7.11.23) |
- RPS6KA5
- RPS6KA4
- P70S6 kinase
- P70-S6 Kinase 1
- RPS6KB2
- RPS6KA2
- RPS6KA3
- RPS6KA1
- RPS6KC1
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| Mitogen-activated protein kinase (EC 2.7.11.24) |
- Extracellular signal-regulated
- MAPK1
- MAPK3
- MAPK4
- MAPK6
- MAPK7
- MAPK12
- MAPK15
- C-Jun N-terminal
- P38 mitogen-activated protein
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| MAP3K (EC 2.7.11.25) |
- MAP kinase kinase kinases
- MAP3K1
- MAP3K2
- MAP3K3
- MAP3K4
- MAP3K5
- MAP3K6
- MAP3K7
- MAP3K8
- RAFs
- MLKs
- MAP3K12
- MAP3K13
- MAP3K9
- MAP3K10
- MAP3K11
- MAP3K7
- ZAK
- CDC7
- MAP3K14
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| Tau-protein kinase (EC 2.7.11.26) |
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| (acetyl-CoA carboxylase) kinase (EC 2.7.11.27) |
-
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| Tropomyosin kinase (EC 2.7.11.28) |
-
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| Low-density-lipoprotein receptor kinase (EC 2.7.11.29) |
-
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| Receptor protein serine/threonine kinase (EC 2.7.11.30) |
- Bone morphogenetic protein receptors
- BMPR1
- BMPR1A
- BMPR1B
- BMPR2
- ACVR1
- ACVR1B
- ACVR1C
- ACVR2A
- ACVR2B
- ACVRL1
- Anti-Müllerian hormone receptor
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Dual-specificity kinases (EC 2.7.12)
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| MAP2K |
- MAP2K1
- MAP2K2
- MAP2K3
- MAP2K4
- MAP2K5
- MAP2K6
- MAP2K7
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- B
- enzm
- 1.1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
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- 11
- 13
- 14
- 15-18
- 2.1
- 3.1
- 4.1
- 5.1
- 6.1-3
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English Journal
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- Chen H, Landen CN, Li Y, Alvarez RD, Tollefsbol TO.SourceDepartment of Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
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- Journal of human hypertension.J Hum Hypertens.2013 Mar 7. doi: 10.1038/jhh.2013.4. [Epub ahead of print]
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- [Non-invasive monitoring of the timing of early embryo cleavages--objectively measurable predictor of human embryo viability].
- Hlinka D, Lazarovská S, Rutarová J, Pichlerová M, Rezácová J, Dudás M.SourcePrague Fertility Centre, Praha.
- Ceská gynekologie / Ceská lékarská spolecnost J. Ev. Purkyne.Ceska Gynekol.2012 Feb;77(1):52-7.
- OBJECTIVE: The evaluation of the developmental abilities of human embryos according to the timing of their early mitotic cleavages.DESIGN: Retrospective study.SETTING: Prague Fertility Centre and Institute for Care of Mother and Child, CAR, Prague.METHODS: The embryos obtained in IVF program were us
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Japanese Journal
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Related Links
- 2011年2月18日 ... AKG IP2全国各地のお店の価格情報がリアルタイムにわかるのは価格.comならでは。 製品レビューやクチコミもあります。
- モニター用カナル型イヤホン。見た目はちょっと地味ですが、音質はフラットでキメの 細かい明瞭なサウンドが特徴。イヤホンながら、AKGのヘッドホンサウンドを楽しむこと が出来ます。
Related Pictures
★リンクテーブル★
[★]
イノシトール二リン酸、イノシトール2リン酸
- 関
- IP2
[★]
- 英
- inositol bisphosphate、IP2
- 関
- イノシトール2リン酸
[★]
- 同
- phosphatidylinositol 4,5-bisphosphate
[★]
[★]