MLLT4
Afadin is a protein that in humans is encoded by the MLLT4 gene.[1]
AF6 is a Ras (see HRAS; MIM 190020) target that regulates cell–cell adhesions downstream of Ras activation. It is fused with MLL (MIM 159555) in leukemias caused by t(6;11) translocations (Taya et al., 1998).[supplied by OMIM][2]
Interactions
MLLT4 has been shown to interact with F11 receptor,[3] RAP1A,[4] LMO2,[5] EPHB3,[6] RAP1GAP,[7] PVRL1,[8] PVRL3,[9][10] USP9X,[11][12] SORBS1,[13] BCR gene,[14] Tight junction protein 1,[15] Profilin 1,[4] HRAS[4][15] and SSX2IP.[16]
References
- ^ Prasad R, Gu Y, Alder H, Nakamura T, Canaani O, Saito H, Huebner K, Gale RP, Nowell PC, Kuriyama K, et al. (Jan 1994). "Cloning of the ALL-1 fusion partner, the AF-6 gene, involved in acute myeloid leukemias with the t(6;11) chromosome translocation". Cancer Res 53 (23): 5624–8. PMID 8242616.
- ^ "Entrez Gene: MLLT4 myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 4". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4301.
- ^ Ebnet, K; Schulz C U, Meyer Zu Brickwedde M K, Pendl G G, Vestweber D (Sep. 2000). "Junctional adhesion molecule interacts with the PDZ domain-containing proteins AF-6 and ZO-1". J. Biol. Chem. (UNITED STATES) 275 (36): 27979–88. doi:10.1074/jbc.M002363200. ISSN 0021-9258. PMID 10856295.
- ^ a b c Boettner, B; Govek E E, Cross J, Van Aelst L (Aug. 2000). "The junctional multidomain protein AF-6 is a binding partner of the Rap1A GTPase and associates with the actin cytoskeletal regulator profilin". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 97 (16): 9064–9. doi:10.1073/pnas.97.16.9064. ISSN 0027-8424. PMC 16822. PMID 10922060. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=16822.
- ^ Bégay-Müller, Valérie; Ansieau Stéphane, Leutz Achim (Jun. 2002). "The LIM domain protein Lmo2 binds to AF6, a translocation partner of the MLL oncogene". FEBS Lett. (Netherlands) 521 (1–3): 36–8. doi:10.1016/S0014-5793(02)02814-4. ISSN 0014-5793. PMID 12067721.
- ^ Hock, B; Böhme B, Karn T, Yamamoto T, Kaibuchi K, Holtrich U, Holland S, Pawson T, Rübsamen-Waigmann H, Strebhardt K (Aug. 1998). "PDZ-domain-mediated interaction of the Eph-related receptor tyrosine kinase EphB3 and the ras-binding protein AF6 depends on the kinase activity of the receptor". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 95 (17): 9779–84. doi:10.1073/pnas.95.17.9779. ISSN 0027-8424. PMC 21413. PMID 9707552. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=21413.
- ^ Su, Li; Hattori Masakazu, Moriyama Masaki, Murata Norihito, Harazaki Masashi, Kaibuchi Kozo, Minato Nagahiro (Apr. 2003). "AF-6 controls integrin-mediated cell adhesion by regulating Rap1 activation through the specific recruitment of Rap1GTP and SPA-1". J. Biol. Chem. (United States) 278 (17): 15232–8. doi:10.1074/jbc.M211888200. ISSN 0021-9258. PMID 12590145.
- ^ Takahashi, K; Nakanishi H, Miyahara M, Mandai K, Satoh K, Satoh A, Nishioka H, Aoki J, Nomoto A, Mizoguchi A, Takai Y (May. 1999). "Nectin/PRR: an immunoglobulin-like cell adhesion molecule recruited to cadherin-based adherens junctions through interaction with Afadin, a PDZ domain-containing protein". J. Cell Biol. (UNITED STATES) 145 (3): 539–49. doi:10.1083/jcb.145.3.539. ISSN 0021-9525. PMC 2185068. PMID 10225955. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2185068.
- ^ Satoh-Horikawa, K; Nakanishi H, Takahashi K, Miyahara M, Nishimura M, Tachibana K, Mizoguchi A, Takai Y (Apr. 2000). "Nectin-3, a new member of immunoglobulin-like cell adhesion molecules that shows homophilic and heterophilic cell-cell adhesion activities". J. Biol. Chem. (UNITED STATES) 275 (14): 10291–9. doi:10.1074/jbc.275.14.10291. ISSN 0021-9258. PMID 10744716.
- ^ Reymond, N; Borg J P, Lecocq E, Adelaide J, Campadelli-Fiume G, Dubreuil P, Lopez M (Sep. 2000). "Human nectin3/PRR3: a novel member of the PVR/PRR/nectin family that interacts with afadin". Gene (NETHERLANDS) 255 (2): 347–55. doi:10.1016/S0378-1119(00)00316-4. ISSN 0378-1119. PMID 11024295.
- ^ Taya, S; Yamamoto T, Kanai-Azuma M, Wood S A, Kaibuchi K (Dec. 1999). "The deubiquitinating enzyme Fam interacts with and stabilizes beta-catenin". Genes Cells (ENGLAND) 4 (12): 757–67. doi:10.1046/j.1365-2443.1999.00297.x. ISSN 1356-9597. PMID 10620020.
- ^ Taya, S; Yamamoto T, Kano K, Kawano Y, Iwamatsu A, Tsuchiya T, Tanaka K, Kanai-Azuma M, Wood S A, Mattick J S, Kaibuchi K (Aug. 1998). "The Ras target AF-6 is a substrate of the fam deubiquitinating enzyme". J. Cell Biol. (UNITED STATES) 142 (4): 1053–62. doi:10.1083/jcb.142.4.1053. ISSN 0021-9525. PMC 2132865. PMID 9722616. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2132865.
- ^ Mandai, K; Nakanishi H, Satoh A, Takahashi K, Satoh K, Nishioka H, Mizoguchi A, Takai Y (Mar. 1999). "Ponsin/SH3P12: an l-afadin- and vinculin-binding protein localized at cell-cell and cell-matrix adherens junctions". J. Cell Biol. (UNITED STATES) 144 (5): 1001–17. doi:10.1083/jcb.144.5.1001. ISSN 0021-9525. PMC 2148189. PMID 10085297. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2148189.
- ^ Radziwill, G; Erdmann R A, Margelisch U, Moelling K (Jul. 2003). "The Bcr kinase downregulates Ras signaling by phosphorylating AF-6 and binding to its PDZ domain". Mol. Cell. Biol. (United States) 23 (13): 4663–72. doi:10.1128/MCB.23.13.4663-4672.2003. ISSN 0270-7306. PMC 164848. PMID 12808105. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=164848.
- ^ a b Yamamoto, T; Harada N, Kawano Y, Taya S, Kaibuchi K (May. 1999). "In vivo interaction of AF-6 with activated Ras and ZO-1". Biochem. Biophys. Res. Commun. (UNITED STATES) 259 (1): 103–7. doi:10.1006/bbrc.1999.0731. ISSN 0006-291X. PMID 10334923.
- ^ Asada, Masanori; Irie Kenji, Morimoto Koji, Yamada Akio, Ikeda Wataru, Takeuchi Masakazu, Takai Yoshimi (Feb. 2003). "ADIP, a novel Afadin- and alpha-actinin-binding protein localized at cell-cell adherens junctions". J. Biol. Chem. (United States) 278 (6): 4103–11. doi:10.1074/jbc.M209832200. ISSN 0021-9258. PMID 12446711.
Further reading
- Takai Y, Nakanishi H (2003). "Nectin and afadin: novel organizers of intercellular junctions.". J. Cell. Sci. 116 (Pt 1): 17–27. doi:10.1242/jcs.00167. PMID 12456712.
- Saha V, Lillington DM, Shelling AN, et al. (1996). "AF6 gene on chromosome band 6q27 maps distal to the minimal region of deletion in epithelial ovarian cancer.". Genes Chromosomes Cancer 14 (3): 220–2. doi:10.1002/gcc.2870140311. PMID 8589040.
- Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery.". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
- Mandai K, Nakanishi H, Satoh A, et al. (1997). "Afadin: A novel actin filament-binding protein with one PDZ domain localized at cadherin-based cell-to-cell adherens junction.". J. Cell Biol. 139 (2): 517–28. doi:10.1083/jcb.139.2.517. PMC 2139800. PMID 9334353. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2139800.
- Joh T, Yamamoto K, Kagami Y, et al. (1997). "Chimeric MLL products with a Ras binding cytoplasmic protein AF6 involved in t(6;11) (q27;q23) leukemia localize in the nucleus.". Oncogene 15 (14): 1681–7. doi:10.1038/sj.onc.1201332. PMID 9349501.
- Saito S, Matsushima M, Shirahama S, et al. (1998). "Complete genomic structure DNA polymorphisms, and alternative splicing of the human AF-6 gene.". DNA Res. 5 (2): 115–20. doi:10.1093/dnares/5.2.115. PMID 9679199.
- Hock B, Böhme B, Karn T, et al. (1998). "PDZ-domain-mediated interaction of the Eph-related receptor tyrosine kinase EphB3 and the ras-binding protein AF6 depends on the kinase activity of the receptor.". Proc. Natl. Acad. Sci. U.S.A. 95 (17): 9779–84. doi:10.1073/pnas.95.17.9779. PMC 21413. PMID 9707552. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=21413.
- Taya S, Yamamoto T, Kano K, et al. (1998). "The Ras target AF-6 is a substrate of the fam deubiquitinating enzyme.". J. Cell Biol. 142 (4): 1053–62. doi:10.1083/jcb.142.4.1053. PMC 2132865. PMID 9722616. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2132865.
- Mandai K, Nakanishi H, Satoh A, et al. (1999). "Ponsin/SH3P12: an l-afadin- and vinculin-binding protein localized at cell-cell and cell-matrix adherens junctions.". J. Cell Biol. 144 (5): 1001–17. doi:10.1083/jcb.144.5.1001. PMC 2148189. PMID 10085297. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2148189.
- Linnemann T, Geyer M, Jaitner BK, et al. (1999). "Thermodynamic and kinetic characterization of the interaction between the Ras binding domain of AF6 and members of the Ras subfamily.". J. Biol. Chem. 274 (19): 13556–62. doi:10.1074/jbc.274.19.13556. PMID 10224125.
- Takahashi K, Nakanishi H, Miyahara M, et al. (1999). "Nectin/PRR: an immunoglobulin-like cell adhesion molecule recruited to cadherin-based adherens junctions through interaction with Afadin, a PDZ domain-containing protein.". J. Cell Biol. 145 (3): 539–49. doi:10.1083/jcb.145.3.539. PMC 2185068. PMID 10225955. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2185068.
- Yamamoto T, Harada N, Kawano Y, et al. (1999). "In vivo interaction of AF-6 with activated Ras and ZO-1.". Biochem. Biophys. Res. Commun. 259 (1): 103–7. doi:10.1006/bbrc.1999.0731. PMID 10334923.
- Minaguchi T, Matsushima M, Saito S, et al. (1999). "Complete DNA sequence and characterization of a 330-kb VNTR-rich region on chromosome 6q27 that is commonly deleted in ovarian cancer.". DNA Res. 6 (2): 131–6. doi:10.1093/dnares/6.2.131. PMID 10382971.
- Quilliam LA, Castro AF, Rogers-Graham KS, et al. (1999). "M-Ras/R-Ras3, a transforming ras protein regulated by Sos1, GRF1, and p120 Ras GTPase-activating protein, interacts with the putative Ras effector AF6.". J. Biol. Chem. 274 (34): 23850–7. doi:10.1074/jbc.274.34.23850. PMID 10446149.
- Kawabe H, Hata Y, Takeuchi M, et al. (1999). "nArgBP2, a novel neural member of ponsin/ArgBP2/vinexin family that interacts with synapse-associated protein 90/postsynaptic density-95-associated protein (SAPAP).". J. Biol. Chem. 274 (43): 30914–8. doi:10.1074/jbc.274.43.30914. PMID 10521485.
- Shao H, Kadono-Okuda K, Finlin BS, Andres DA (1999). "Biochemical characterization of the Ras-related GTPases Rit and Rin.". Arch. Biochem. Biophys. 371 (2): 207–19. doi:10.1006/abbi.1999.1448. PMID 10545207.
- Asakura T, Nakanishi H, Sakisaka T, et al. (2000). "Similar and differential behaviour between the nectin-afadin-ponsin and cadherin-catenin systems during the formation and disruption of the polarized junctional alignment in epithelial cells.". Genes Cells 4 (10): 573–81. doi:10.1046/j.1365-2443.1999.00283.x. PMID 10583506.
- Miyahara M, Nakanishi H, Takahashi K, et al. (2000). "Interaction of nectin with afadin is necessary for its clustering at cell-cell contact sites but not for its cis dimerization or trans interaction.". J. Biol. Chem. 275 (1): 613–8. doi:10.1074/jbc.275.1.613. PMID 10617658.
- Bouchard MJ, Dong Y, McDermott BM, et al. (2000). "Defects in nuclear and cytoskeletal morphology and mitochondrial localization in spermatozoa of mice lacking nectin-2, a component of cell-cell adherens junctions.". Mol. Cell. Biol. 20 (8): 2865–73. doi:10.1128/MCB.20.8.2865-2873.2000. PMC 85510. PMID 10733589. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=85510.
PDB gallery
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1t2m: Solution Structure Of The Pdz Domain Of AF-6
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1wln: Solution structure of the FHA domain of mouse Afadin 6
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1wxa: Solution Structure of Ras-binding Domain in Mouse AF-6 Protein
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1xz9: Structure of AF-6 PDZ domain
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2ain: Solution structure of the AF-6 PDZ domain complexed with the C-terminal peptide from the Bcr protein
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2exg: Making Protein-Protein Interactions Drugable: Discovery of Low-Molecular-Weight Ligands for the AF6 PDZ Domain
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