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Myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 4
Protein MLLT4 PDB 1t2m.png
PDB rendering based on 1t2m.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols MLLT4 ; 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:
168.23 – 168.37 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 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]


  1. ^ Prasad R, Gu Y, Alder H, Nakamura T, Canaani O, Saito H, Huebner K, Gale RP, Nowell PC, Kuriyama K et al. (January 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. 
  2. ^ "Entrez Gene: MLLT4 myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 4". 
  3. ^ Ebnet, K; Schulz C U, Meyer Zu Brickwedde M K, Pendl G G, Vestweber D (September 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. 
  4. ^ a b c Boettner, B; Govek E E; Cross J; Van Aelst L (August 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. 
  5. ^ Bégay-Müller, Valérie; Ansieau Stéphane; Leutz Achim (June 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. 
  6. ^ Hock, B; Böhme B; Karn T; Yamamoto T; Kaibuchi K; Holtrich U; Holland S; Pawson T; Rübsamen-Waigmann H; Strebhardt K (August 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. 
  7. ^ Su, Li; Hattori Masakazu; Moriyama Masaki; Murata Norihito; Harazaki Masashi; Kaibuchi Kozo; Minato Nagahiro (April 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. 
  8. ^ 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. 
  9. ^ Satoh-Horikawa, K; Nakanishi H; Takahashi K; Miyahara M; Nishimura M; Tachibana K; Mizoguchi A; Takai Y (April 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. 
  10. ^ Reymond, N; Borg J P; Lecocq E; Adelaide J; Campadelli-Fiume G; Dubreuil P; Lopez M (September 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. 
  11. ^ Taya, S; Yamamoto T; Kanai-Azuma M; Wood S A; Kaibuchi K (December 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. 
  12. ^ 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 (August 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. 
  13. ^ Mandai, K; Nakanishi H; Satoh A; Takahashi K; Satoh K; Nishioka H; Mizoguchi A; Takai Y (March 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. 
  14. ^ Radziwill, G; Erdmann R A; Margelisch U; Moelling K (July 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. 
  15. ^ 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. 
  16. ^ Asada, Masanori; Irie Kenji; Morimoto Koji; Yamada Akio; Ikeda Wataru; Takeuchi Masakazu; Takai Yoshimi (February 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[edit]