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(Top) 1 Function 2 Interactions 3 References 4 Further reading

Afadin

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AFDN

Available structures

PDB

Ortholog search: PDBe RCSB

List of PDB id codes
1T2M, 1XZ9, 2AIN, 2EXG, 5A6C

Identifiers

Aliases

AFDN, AF6, MLL-AF6, MLLT4, myeloid/lymphoid or mixed-lineage leukemia; translocated to, 4, afadin, adherens junction formation factor, l-afadin

External IDs

OMIM: 159559; MGI: 1314653; HomoloGene: 21202; GeneCards: AFDN; OMA:AFDN - orthologs

Gene location (Human)

Chr.	Chromosome 6 (human)^[1]

Band	6q27	Start	167,826,911 bp^[1]
Band	6q27	End	167,972,023 bp^[1]

Gene location (Mouse)

Chr.	Chromosome 17 (mouse)^[2]

Band	17\|17 A1- A2	Start	13,980,801 bp^[2]
Band	17\|17 A1- A2	End	14,126,412 bp^[2]

RNA expression pattern

Bgee

Human

Mouse (ortholog)

Top expressed in

right uterine tube

sural nerve

bronchial epithelial cell

ganglionic eminence

right lung

buccal mucosa cell

minor salivary glands

body of pancreas

rectum

caput epididymis

Top expressed in

superior cervical ganglion

hair follicle

skin of abdomen

skin of external ear

gastrula

otolith organ

utricle

conjunctival fornix

medullary collecting duct

More reference expression data

BioGPS


More reference expression data

Gene ontology
Molecular function	protein C-terminus binding protein binding cadherin binding cell adhesion molecule binding actin filament binding
Cellular component	adherens junction cell junction plasma membrane nucleoplasm cytosol cell-cell junction nuclear speck cell-cell contact zone tight junctions
Biological process	cell-cell signaling positive regulation of GTPase activity cell adhesion establishment of endothelial intestinal barrier signal transduction regulation of protein localization adherens junction organization positive regulation of gene expression positive regulation of cell-cell adhesion negative regulation of cell migration cell-cell adhesion mediated by cadherin establishment of protein localization to plasma membrane bicellular tight junction assembly positive regulation of cell-cell adhesion mediated by cadherin
Sources:Amigo / QuickGO

Orthologs

Species

Human

Mouse

Entrez


4301


17356

Ensembl


ENSG00000130396


ENSMUSG00000068036

UniProt


P55196


Q9QZQ1

RefSeq (mRNA)

NM_001040000 NM_001040001 NM_001207008 NM_001291964 NM_005936
NM_001366319 NM_001366320 NM_001366321 NM_001386888


NM_010806

RefSeq (protein)

NP_001035089 NP_001193937 NP_001278893 NP_001353248 NP_001353249
NP_001353250


NP_034936

Location (UCSC)

Chr 6: 167.83 – 167.97 Mb

Chr 17: 13.98 – 14.13 Mb

PubMed search

^[3]

^[4]

Wikidata

View/Edit Human

View/Edit Mouse

Afadin is a protein that in humans is encoded by the AFDN gene.^[5]

Function[edit]

Afadin 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]^[6]

Interactions[edit]

Afadin has been shown to interact with:

BCR gene,^[7]

EPHB3,^[8]

F11 receptor,^[9]

HRAS^[10]^[11] and

LMO2,^[12]

PVRL1,^[13]

PVRL3,^[14]^[15]

Profilin 1,^[10]

RAP1A,^[10]

RAP1GAP,^[16]

SORBS1,^[17]

SSX2IP,^[18]

Tight junction protein 1,^[11] and

USP9X.^[19]^[20]

References[edit]

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000130396 – Ensembl, May 2017

^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000068036 – Ensembl, May 2017

^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

^ 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.

^ "Entrez Gene: MLLT4 myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 4".

^ 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.

^ 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. Bibcode:1998PNAS...95.9779H. doi:10.1073/pnas.95.17.9779. PMC 21413. PMID 9707552.

^ 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.

^ ^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. Bibcode:2000PNAS...97.9064B. doi:10.1073/pnas.97.16.9064. PMC 16822. PMID 10922060.

^ ^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.

^ 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. S2CID 29461336.

^ 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.

^ 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.

^ 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.

^ 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. hdl:2433/148462. PMID 12590145.

^ 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.

^ 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.

^ 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. S2CID 85747886.

^ 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]

Takai Y, Nakanishi H (Jan 2003). "Nectin and afadin: novel organizers of intercellular junctions". Journal of Cell Science. 116 (Pt 1): 17–27. CiteSeerX 10.1.1.321.6596. doi:10.1242/jcs.00167. PMID 12456712. S2CID 6465469.

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. S2CID 23752846.

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. Bibcode:1998PNAS...95.9779H. 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. S2CID 24023429.

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.

PDB gallery

1t2m: Solution Structure Of The Pdz Domain Of AF-6

1wln: Solution structure of the FHA domain of mouse Afadin 6

1wxa: Solution Structure of Ras-binding Domain in Mouse AF-6 Protein

1xz9: Structure of AF-6 PDZ domain

2ain: Solution structure of the AF-6 PDZ domain complexed with the C-terminal peptide from the Bcr protein

2exg: Making Protein-Protein Interactions Drugable: Discovery of Low-Molecular-Weight Ligands for the AF6 PDZ Domain

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