MLLT4

Myeloid/lymphoid or mixed-lineage leukemia; translocated to, 4
PDB rendering based on 1t2m.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1T2M​, 1XZ9​, 2AIN​, 2EXG​
Identifiers
Symbols	MLLT4 ; AF6; MLL-AF6
External IDs	OMIM: 159559 MGI: 1314653 HomoloGene: 21202 GeneCards: MLLT4 Gene
Gene ontology Molecular function • protein binding • protein C-terminus binding • Ras GTPase binding • cell adhesion molecule binding Cellular component • nucleoplasm • cytoplasm • cytosol • plasma membrane • cell-cell junction • cell-cell adherens junction • cell junction • apical part of cell Biological process • cell adhesion • signal transduction • cell-cell signaling • cell junction assembly • adherens junction organization • positive regulation of GTPase activity • cell-cell junction organization • establishment of endothelial intestinal barrier Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	4301	17356
Ensembl	ENSG00000130396	ENSMUSG00000068036
UniProt	P55196	Q9QZQ1
RefSeq (mRNA)	NM_001040000	NM_010806
RefSeq (protein)	NP_001035089	NP_034936
Location (UCSC)	Chr 6: 167.83 – 167.97 Mb	Chr 17: 13.76 – 13.91 Mb
PubMed search

Afadin is a protein that in humans is encoded by the MLLT4 gene.^[1]

Function

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:

• BCR gene,^[3]
• EPHB3,^[4]
• F11 receptor,^[5]
• HRAS^[6][7] and
• LMO2,^[8]
• PVRL1,^[9]
• PVRL3,^[10][11]
• Profilin 1,^[6]
• RAP1A,^[6]
• RAP1GAP,^[12]
• SORBS1,^[13]
• SSX2IP,^[14]
• Tight junction protein 1,^[7] and
• USP9X.^[15][16]

References

1. Prasad R, Gu Y, Alder H, Nakamura T, Canaani O, Saito H, Huebner K, Gale RP, Nowell PC, Kuriyama K (Dec 1993). "Cloning of the ALL-1 fusion partner, the AF-6 gene, involved in acute myeloid leukemias with the t(6;11) chromosome translocation". Cancer Research 53 (23): 5624–8. PMID 8242616.
2. "Entrez Gene: MLLT4 myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 4".
3. Radziwill G, Erdmann RA, Margelisch U, Moelling K (Jul 2003). "The Bcr kinase downregulates Ras signaling by phosphorylating AF-6 and binding to its PDZ domain". Molecular and Cellular Biology 23 (13): 4663–72. doi:10.1128/mcb.23.13.4663-4672.2003. PMC 164848. PMID 12808105.
4. 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". Proceedings of the National Academy of Sciences of the United States of America 95 (17): 9779–84. doi:10.1073/pnas.95.17.9779. PMC 21413. PMID 9707552.
5. Ebnet K, Schulz CU, Meyer Zu Brickwedde MK, Pendl GG, Vestweber D (Sep 2000). "Junctional adhesion molecule interacts with the PDZ domain-containing proteins AF-6 and ZO-1". The Journal of Biological Chemistry 275 (36): 27979–88. doi:10.1074/jbc.M002363200. PMID 10856295.
6. Boettner B, Govek EE, 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". Proceedings of the National Academy of Sciences of the United States of America 97 (16): 9064–9. doi:10.1073/pnas.97.16.9064. PMC 16822. PMID 10922060.
7. Yamamoto T, Harada N, Kawano Y, Taya S, Kaibuchi K (May 1999). "In vivo interaction of AF-6 with activated Ras and ZO-1". Biochemical and Biophysical Research Communications 259 (1): 103–7. doi:10.1006/bbrc.1999.0731. PMID 10334923.
8. Bégay-Müller V, Ansieau S, Leutz A (Jun 2002). "The LIM domain protein Lmo2 binds to AF6, a translocation partner of the MLL oncogene". FEBS Letters 521 (1-3): 36–8. doi:10.1016/s0014-5793(02)02814-4. PMID 12067721.
9. 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". The Journal of Cell Biology 145 (3): 539–49. doi:10.1083/jcb.145.3.539. PMC 2185068. PMID 10225955.
10. 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". The Journal of Biological Chemistry 275 (14): 10291–9. doi:10.1074/jbc.275.14.10291. PMID 10744716.
11. Reymond N, Borg JP, 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 255 (2): 347–55. doi:10.1016/s0378-1119(00)00316-4. PMID 11024295.
12. Su L, Hattori M, Moriyama M, Murata N, Harazaki M, Kaibuchi K, Minato N (Apr 2003). "AF-6 controls integrin-mediated cell adhesion by regulating Rap1 activation through the specific recruitment of Rap1GTP and SPA-1". The Journal of Biological Chemistry 278 (17): 15232–8. doi:10.1074/jbc.M211888200. PMID 12590145.
13. 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". The Journal of Cell Biology 144 (5): 1001–17. doi:10.1083/jcb.144.5.1001. PMC 2148189. PMID 10085297.
14. Asada M, Irie K, Morimoto K, Yamada A, Ikeda W, Takeuchi M, Takai Y (Feb 2003). "ADIP, a novel Afadin- and alpha-actinin-binding protein localized at cell-cell adherens junctions". The Journal of Biological Chemistry 278 (6): 4103–11. doi:10.1074/jbc.M209832200. PMID 12446711.
15. Taya S, Yamamoto T, Kanai-Azuma M, Wood SA, Kaibuchi K (Dec 1999). "The deubiquitinating enzyme Fam interacts with and stabilizes beta-catenin". Genes to Cells 4 (12): 757–67. doi:10.1046/j.1365-2443.1999.00297.x. PMID 10620020.
16. Taya S, Yamamoto T, Kano K, Kawano Y, Iwamatsu A, Tsuchiya T, Tanaka K, Kanai-Azuma M, Wood SA, Mattick JS, Kaibuchi K (Aug 1998). "The Ras target AF-6 is a substrate of the fam deubiquitinating enzyme". The Journal of Cell Biology 142 (4): 1053–62. doi:10.1083/jcb.142.4.1053. PMC 2132865. PMID 9722616.

Further reading

• Takai Y, Nakanishi H (Jan 2003). "Nectin and afadin: novel organizers of intercellular junctions". Journal of Cell Science 116 (Pt 1): 17–27. doi:10.1242/jcs.00167. PMID 12456712.
• Saha V, Lillington DM, Shelling AN, Chaplin T, Yaspo ML, Ganesan TS, Young BD (Nov 1995). "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 (Sep 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
• Mandai K, Nakanishi H, Satoh A, Obaishi H, Wada M, Nishioka H, Itoh M, Mizoguchi A, Aoki T, Fujimoto T, Matsuda Y, Tsukita S, Takai Y (Oct 1997). "Afadin: A novel actin filament-binding protein with one PDZ domain localized at cadherin-based cell-to-cell adherens junction". The Journal of Cell Biology 139 (2): 517–28. doi:10.1083/jcb.139.2.517. PMC 2139800. PMID 9334353.
• Joh T, Yamamoto K, Kagami Y, Kakuda H, Sato T, Yamamoto T, Takahashi T, Ueda R, Kaibuchi K, Seto M (Oct 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, Minaguchi T, Kanamori Y, Minami M, Nakamura Y (Apr 1998). "Complete genomic structure DNA polymorphisms, and alternative splicing of the human AF-6 gene". DNA Research 5 (2): 115–20. doi:10.1093/dnares/5.2.115. PMID 9679199.
• 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". Proceedings of the National Academy of Sciences of the United States of America 95 (17): 9779–84. doi:10.1073/pnas.95.17.9779. PMC 21413. PMID 9707552.
• Taya S, Yamamoto T, Kano K, Kawano Y, Iwamatsu A, Tsuchiya T, Tanaka K, Kanai-Azuma M, Wood SA, Mattick JS, Kaibuchi K (Aug 1998). "The Ras target AF-6 is a substrate of the fam deubiquitinating enzyme". The Journal of Cell Biology 142 (4): 1053–62. doi:10.1083/jcb.142.4.1053. PMC 2132865. PMID 9722616.
• 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". The Journal of Cell Biology 144 (5): 1001–17. doi:10.1083/jcb.144.5.1001. PMC 2148189. PMID 10085297.
• Linnemann T, Geyer M, Jaitner BK, Block C, Kalbitzer HR, Wittinghofer A, Herrmann C (May 1999). "Thermodynamic and kinetic characterization of the interaction between the Ras binding domain of AF6 and members of the Ras subfamily". The Journal of Biological Chemistry 274 (19): 13556–62. doi:10.1074/jbc.274.19.13556. PMID 10224125.
• 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". The Journal of Cell Biology 145 (3): 539–49. doi:10.1083/jcb.145.3.539. PMC 2185068. PMID 10225955.
• Yamamoto T, Harada N, Kawano Y, Taya S, Kaibuchi K (May 1999). "In vivo interaction of AF-6 with activated Ras and ZO-1". Biochemical and Biophysical Research Communications 259 (1): 103–7. doi:10.1006/bbrc.1999.0731. PMID 10334923.
• Minaguchi T, Matsushima M, Saito S, Kanamori Y, Shirahama S, Okamoto S, Minami M, Taketani Y, Nakamura Y (Apr 1999). "Complete DNA sequence and characterization of a 330-kb VNTR-rich region on chromosome 6q27 that is commonly deleted in ovarian cancer". DNA Research 6 (2): 131–6. doi:10.1093/dnares/6.2.131. PMID 10382971.
• Quilliam LA, Castro AF, Rogers-Graham KS, Martin CB, Der CJ, Bi C (Aug 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". The Journal of Biological Chemistry 274 (34): 23850–7. doi:10.1074/jbc.274.34.23850. PMID 10446149.
• Kawabe H, Hata Y, Takeuchi M, Ide N, Mizoguchi A, Takai Y (Oct 1999). "nArgBP2, a novel neural member of ponsin/ArgBP2/vinexin family that interacts with synapse-associated protein 90/postsynaptic density-95-associated protein (SAPAP)". The Journal of Biological Chemistry 274 (43): 30914–8. doi:10.1074/jbc.274.43.30914. PMID 10521485.
• Shao H, Kadono-Okuda K, Finlin BS, Andres DA (Nov 1999). "Biochemical characterization of the Ras-related GTPases Rit and Rin". Archives of Biochemistry and Biophysics 371 (2): 207–19. doi:10.1006/abbi.1999.1448. PMID 10545207.
• Asakura T, Nakanishi H, Sakisaka T, Takahashi K, Mandai K, Nishimura M, Sasaki T, Takai Y (Oct 1999). "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 to Cells 4 (10): 573–81. doi:10.1046/j.1365-2443.1999.00283.x. PMID 10583506.
• Miyahara M, Nakanishi H, Takahashi K, Satoh-Horikawa K, Tachibana K, Takai Y (Jan 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". The Journal of Biological Chemistry 275 (1): 613–8. doi:10.1074/jbc.275.1.613. PMID 10617658.
• Bouchard MJ, Dong Y, McDermott BM, Lam DH, Brown KR, Shelanski M, Bellvé AR, Racaniello VR (Apr 2000). "Defects in nuclear and cytoskeletal morphology and mitochondrial localization in spermatozoa of mice lacking nectin-2, a component of cell-cell adherens junctions". Molecular and Cellular Biology 20 (8): 2865–73. doi:10.1128/MCB.20.8.2865-2873.2000. PMC 85510. PMID 10733589.