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Myeloid/lymphoid or mixed-lineage leukemia; translocated to, 4
Protein MLLT4 PDB 1t2m.png
PDB rendering based on 1t2m.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols MLLT4 ; AF6; MLL-AF6
External IDs OMIM159559 MGI1314653 HomoloGene21202 GeneCards: MLLT4 Gene
RNA expression pattern
PBB GE MLLT4 208512 s at tn.png
PBB GE MLLT4 214939 x at tn.png
PBB GE MLLT4 215904 at tn.png
More reference expression data
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 [1] [2]

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]


MLLT4 has been shown to interact with:


  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. ^ a b c 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. ^ 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". 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[edit]