ID AFAD_HUMAN Reviewed; 1824 AA. AC P55196; O75087; O75088; O75089; Q59FP0; Q5TIG6; Q5TIG7; Q9NSN7; Q9NU92; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 09-FEB-2010, sequence version 3. DT 27-MAR-2024, entry version 229. DE RecName: Full=Afadin; DE AltName: Full=ALL1-fused gene from chromosome 6 protein; DE Short=Protein AF-6; DE AltName: Full=Afadin adherens junction formation factor {ECO:0000312|HGNC:HGNC:7137}; GN Name=AFDN {ECO:0000312|HGNC:HGNC:7137}; Synonyms=AF6, MLLT4; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND CHROMOSOMAL TRANSLOCATION WITH RP KMT2A. RX PubMed=8242616; RA Prasad R., Gu Y., Alder H., Nakamura T., Canaani O., Saito H., Huebner K., RA Gale R.P., Nowell P.C., Kuriyama K., Miyazaki Y., Croce C.M., Canaani E.; RT "Cloning of the ALL-1 fusion partner, the AF-6 gene, involved in acute RT myeloid leukemias with the t(6;11) chromosome translocation."; RL Cancer Res. 53:5624-5628(1993). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING (ISOFORMS 1; 2 RP AND 3). RC TISSUE=Fetal brain; RX PubMed=9679199; DOI=10.1093/dnares/5.2.115; RA Saito S., Matsushima M., Shirahama S., Minaguchi T., Kanamori Y., RA Minami M., Nakamura Y.; RT "Complete genomic structure, DNA polymorphisms, and alternative splicing of RT the human AF-6 gene."; RL DNA Res. 5:115-120(1998). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., RA Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 13-1824 (ISOFORM 6). RC TISSUE=Brain; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., RA Ohara O., Nagase T., Kikuno R.F.; RT "Homo sapiens protein coding cDNA."; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 335-1824 (ISOFORM 5). RC TISSUE=Amygdala; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [7] RP FUNCTION, AND INTERACTION WITH NECTIN3. RX PubMed=11024295; DOI=10.1016/s0378-1119(00)00316-4; RA Reymond N., Borg J.-P., Lecocq E., Adelaide J., Campadelli-Fiume G., RA Dubreuil P., Lopez M.; RT "Human nectin3/PRR3: a novel member of the PVR/PRR/nectin family that RT interacts with afadin."; RL Gene 255:347-355(2000). RN [8] RP REVIEW ON INTERACTION. RX PubMed=12456712; DOI=10.1242/jcs.00167; RA Takai Y., Nakanishi H.; RT "Nectin and afadin: novel organizers of intercellular junctions."; RL J. Cell Sci. 116:17-27(2003). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1182, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=15144186; DOI=10.1021/ac035352d; RA Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M., RA Peters E.C.; RT "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from RT human T cells using immobilized metal affinity chromatography and tandem RT mass spectrometry."; RL Anal. Chem. 76:2763-2772(2004). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1182, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic kidney; RX PubMed=17693683; DOI=10.1074/mcp.m700120-mcp200; RA Tang L.-Y., Deng N., Wang L.-S., Dai J., Wang Z.-L., Jiang X.-S., Li S.-J., RA Li L., Sheng Q.-H., Wu D.-Q., Li L., Zeng R.; RT "Quantitative phosphoproteome profiling of Wnt3a-mediated signaling RT network: indicating the involvement of ribonucleoside-diphosphate reductase RT M2 subunit phosphorylation at residue serine 20 in canonical Wnt signal RT transduction."; RL Mol. Cell. Proteomics 6:1952-1967(2007). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18220336; DOI=10.1021/pr0705441; RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III; RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient RT phosphoproteomic analysis."; RL J. Proteome Res. 7:1346-1351(2008). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-216; SER-1107; SER-1182; RP THR-1232; SER-1721; SER-1779 AND SER-1799, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1182 AND SER-1721, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1721; SER-1779 AND SER-1799, RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [16] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-216; SER-256; SER-424; RP SER-512; SER-557; SER-562; SER-589; SER-655; SER-1083; SER-1107; SER-1143; RP SER-1173; SER-1182; SER-1199; THR-1232; SER-1238; SER-1275; SER-1328; RP THR-1330; SER-1501; SER-1512 AND SER-1721, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-246; SER-1182; THR-1211; RP SER-1696 AND SER-1799, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [19] RP FUNCTION, INTERACTION WITH ADAM10, AND SUBCELLULAR LOCATION. RX PubMed=30463011; DOI=10.1016/j.celrep.2018.10.088; RA Shah J., Rouaud F., Guerrera D., Vasileva E., Popov L.M., Kelley W.L., RA Rubinstein E., Carette J.E., Amieva M.R., Citi S.; RT "A Dock-and-Lock Mechanism Clusters ADAM10 at Cell-Cell Junctions to RT Promote alpha-Toxin Cytotoxicity."; RL Cell Rep. 25:2132-2147(2018). RN [20] RP STRUCTURE BY NMR OF 1003-1094 IN COMPLEX WITH NRXN1 AND BCR. RX PubMed=15684424; DOI=10.1074/jbc.m411065200; RA Zhou H., Xu Y., Yang Y., Huang A., Wu J., Shi Y.; RT "Solution structure of AF-6 PDZ domain and its interaction with the C- RT terminal peptides from Neurexin and Bcr."; RL J. Biol. Chem. 280:13841-13847(2005). RN [21] RP STRUCTURE BY NMR OF 1001-1095. RX PubMed=16671149; DOI=10.1002/anie.200503965; RA Joshi M., Vargas C., Boisguerin P., Diehl A., Krause G., Schmieder P., RA Moelling K., Hagen V., Schade M., Oschkinat H.; RT "Discovery of low-molecular-weight ligands for the AF6 PDZ domain."; RL Angew. Chem. Int. Ed. 45:3790-3795(2006). CC -!- FUNCTION: Belongs to an adhesion system, probably together with the E- CC cadherin-catenin system, which plays a role in the organization of CC homotypic, interneuronal and heterotypic cell-cell adherens junctions CC (AJs) (By similarity). Nectin- and actin-filament-binding protein that CC connects nectin to the actin cytoskeleton (PubMed:11024295). May play a CC key role in the organization of epithelial structures of the embryonic CC ectoderm (By similarity). Essential for the organization of adherens CC junctions (PubMed:30463011). {ECO:0000250|UniProtKB:O35889, CC ECO:0000250|UniProtKB:Q9QZQ1, ECO:0000269|PubMed:11024295, CC ECO:0000269|PubMed:30463011}. CC -!- SUBUNIT: Homodimer. Interacts with F-actin, nectin and NECTIN3. CC Essential for the association of nectin and E-cadherin. Isoform 1/s- CC afadin does not interact with F-actin. Interacts with ZO-1 and CC occludin, but probably in an indirect manner. Interacts with RIT1 and CC RIT2 (By similarity). Interacts with NRXN1 and BCR. Interacts with CC ADAM10; the interaction locks ADAM10 at adherens junctions following CC ADAM10 recruitment to adherens junctions by TSPAN33 (PubMed:30463011). CC {ECO:0000250, ECO:0000269|PubMed:11024295, ECO:0000269|PubMed:15684424, CC ECO:0000269|PubMed:30463011}. CC -!- INTERACTION: CC P55196; Q16643: DBN1; NbExp=4; IntAct=EBI-365875, EBI-351394; CC P55196; Q92692: NECTIN2; NbExp=2; IntAct=EBI-365875, EBI-718419; CC P55196; P12931: SRC; NbExp=7; IntAct=EBI-365875, EBI-621482; CC -!- SUBCELLULAR LOCATION: Cell junction, adherens junction CC {ECO:0000269|PubMed:30463011}. Note=Not found at cell-matrix AJs. CC {ECO:0000250|UniProtKB:O35889}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=6; CC Name=4; CC IsoId=P55196-4; Sequence=Displayed; CC Name=1; Synonyms=s-afadin; CC IsoId=P55196-2; Sequence=VSP_038707, VSP_038708, VSP_000217, CC VSP_000218; CC Name=2; Synonyms=l-afadin; CC IsoId=P55196-1; Sequence=VSP_038707, VSP_038708, VSP_038709, CC VSP_038711; CC Name=3; CC IsoId=P55196-3; Sequence=VSP_038707, VSP_038708, VSP_038709, CC VSP_038710; CC Name=6; CC IsoId=P55196-6; Sequence=VSP_041197, VSP_041198, VSP_041199; CC Name=5; CC IsoId=P55196-5; Sequence=VSP_038707, VSP_019257; CC -!- DOMAIN: The PDZ/DHR domain interacts with the C-terminus of nectin and CC the Pro-rich C-terminal domain interacts with F-actin. CC -!- DISEASE: Note=A chromosomal aberration involving AFDN is associated CC with acute leukemias. Translocation t(6;11)(q27;q23) with KMT2A/MLL1. CC The result is a rogue activator protein. CC -!- MISCELLANEOUS: [Isoform 1]: May be due to intron retention. CC {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 2]: May be due to intron retention. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=CAB82312.1; Type=Frameshift; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/6/AF6"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U02478; AAC50059.1; -; mRNA. DR EMBL; AB011399; BAA32483.1; -; Genomic_DNA. DR EMBL; AB011399; BAA32484.1; -; Genomic_DNA. DR EMBL; AB011399; BAA32485.1; -; Genomic_DNA. DR EMBL; AL009178; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL049698; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL731868; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471051; EAW47482.1; -; Genomic_DNA. DR EMBL; AB209420; BAD92657.1; -; mRNA. DR EMBL; AL161973; CAB82312.1; ALT_FRAME; mRNA. DR CCDS; CCDS47517.1; -. [P55196-6] DR CCDS; CCDS75553.1; -. [P55196-3] DR CCDS; CCDS94034.1; -. [P55196-4] DR PIR; T47137; T47137. DR RefSeq; NP_001035089.1; NM_001040000.2. [P55196-6] DR RefSeq; NP_001193937.1; NM_001207008.1. [P55196-3] DR RefSeq; NP_001278893.1; NM_001291964.1. DR RefSeq; XP_005267053.1; XM_005266996.3. DR PDB; 1T2M; NMR; -; A=1003-1094. DR PDB; 1XZ9; NMR; -; A=1001-1096. DR PDB; 2AIN; NMR; -; A=1003-1094. DR PDB; 2EXG; NMR; -; A=1001-1096. DR PDB; 5A6C; X-ray; 2.90 A; A/B=1709-1746. DR PDB; 7QCR; X-ray; 2.28 A; A/B=1002-1097. DR PDBsum; 1T2M; -. DR PDBsum; 1XZ9; -. DR PDBsum; 2AIN; -. DR PDBsum; 2EXG; -. DR PDBsum; 5A6C; -. DR PDBsum; 7QCR; -. DR AlphaFoldDB; P55196; -. DR BMRB; P55196; -. DR SMR; P55196; -. DR BioGRID; 110447; 303. DR CORUM; P55196; -. DR ELM; P55196; -. DR IntAct; P55196; 61. DR MINT; P55196; -. DR STRING; 9606.ENSP00000355771; -. DR DrugBank; DB08574; (5R)-2-sulfanyl-5-[4-(trifluoromethyl)benzyl]-1,3-thiazol-4(5H)-one. DR GlyGen; P55196; 4 sites, 1 O-linked glycan (4 sites). DR iPTMnet; P55196; -. DR PhosphoSitePlus; P55196; -. DR SwissPalm; P55196; -. DR BioMuta; AFDN; -. DR DMDM; 288558835; -. DR EPD; P55196; -. DR jPOST; P55196; -. DR MassIVE; P55196; -. DR MaxQB; P55196; -. DR PaxDb; 9606-ENSP00000375960; -. DR PeptideAtlas; P55196; -. DR ProteomicsDB; 56796; -. [P55196-4] DR ProteomicsDB; 56797; -. [P55196-1] DR ProteomicsDB; 56798; -. [P55196-2] DR ProteomicsDB; 56799; -. [P55196-3] DR ProteomicsDB; 56800; -. [P55196-5] DR ProteomicsDB; 56801; -. [P55196-6] DR Pumba; P55196; -. DR Antibodypedia; 4608; 306 antibodies from 33 providers. DR DNASU; 4301; -. DR Ensembl; ENST00000392108.7; ENSP00000375956.3; ENSG00000130396.22. [P55196-6] DR Ensembl; ENST00000392112.5; ENSP00000375960.2; ENSG00000130396.22. [P55196-3] DR Ensembl; ENST00000400822.7; ENSP00000383623.3; ENSG00000130396.22. [P55196-5] DR Ensembl; ENST00000447894.6; ENSP00000404595.2; ENSG00000130396.22. [P55196-4] DR GeneID; 4301; -. DR KEGG; hsa:4301; -. DR UCSC; uc003qwc.3; human. [P55196-4] DR AGR; HGNC:7137; -. DR DisGeNET; 4301; -. DR GeneCards; AFDN; -. DR HGNC; HGNC:7137; AFDN. DR HPA; ENSG00000130396; Low tissue specificity. DR MIM; 159559; gene. DR neXtProt; NX_P55196; -. DR OpenTargets; ENSG00000130396; -. DR VEuPathDB; HostDB:ENSG00000130396; -. DR eggNOG; KOG1892; Eukaryota. DR GeneTree; ENSGT00940000155237; -. DR InParanoid; P55196; -. DR OrthoDB; 2881454at2759; -. DR PhylomeDB; P55196; -. DR TreeFam; TF350731; -. DR PathwayCommons; P55196; -. DR Reactome; R-HSA-418990; Adherens junctions interactions. [P55196-2] DR SignaLink; P55196; -. DR SIGNOR; P55196; -. DR BioGRID-ORCS; 4301; 46 hits in 1162 CRISPR screens. DR ChiTaRS; AFDN; human. DR EvolutionaryTrace; P55196; -. DR GeneWiki; MLLT4; -. DR GenomeRNAi; 4301; -. DR Pharos; P55196; Tbio. DR PRO; PR:P55196; -. DR Proteomes; UP000005640; Chromosome 6. DR RNAct; P55196; Protein. DR Bgee; ENSG00000130396; Expressed in right uterine tube and 181 other cell types or tissues. DR ExpressionAtlas; P55196; baseline and differential. DR GO; GO:0005912; C:adherens junction; IBA:GO_Central. DR GO; GO:0030054; C:cell junction; IDA:HPA. DR GO; GO:0044291; C:cell-cell contact zone; IDA:ARUK-UCL. DR GO; GO:0005911; C:cell-cell junction; IDA:ARUK-UCL. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0016607; C:nuclear speck; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0046930; C:pore complex; IMP:UniProtKB. DR GO; GO:0070160; C:tight junction; IDA:ARUK-UCL. DR GO; GO:0051015; F:actin filament binding; IDA:ARUK-UCL. DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL. DR GO; GO:0050839; F:cell adhesion molecule binding; IBA:GO_Central. DR GO; GO:0031267; F:small GTPase binding; IPI:UniProtKB. DR GO; GO:0070830; P:bicellular tight junction assembly; IMP:ARUK-UCL. DR GO; GO:0007155; P:cell adhesion; TAS:ProtInc. DR GO; GO:0044331; P:cell-cell adhesion mediated by cadherin; ISS:ARUK-UCL. DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc. DR GO; GO:0090557; P:establishment of endothelial intestinal barrier; IMP:UniProtKB. DR GO; GO:0061951; P:establishment of protein localization to plasma membrane; ISS:ARUK-UCL. DR GO; GO:0030336; P:negative regulation of cell migration; IMP:ARUK-UCL. DR GO; GO:0046931; P:pore complex assembly; IMP:UniProtKB. DR GO; GO:0022409; P:positive regulation of cell-cell adhesion; IMP:UniProtKB. DR GO; GO:2000049; P:positive regulation of cell-cell adhesion mediated by cadherin; IMP:ARUK-UCL. DR GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB. DR GO; GO:0032880; P:regulation of protein localization; IBA:GO_Central. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR CDD; cd22711; FHA_AFDN; 1. DR CDD; cd15471; Myo5p-like_CBD_afadin; 1. DR CDD; cd00992; PDZ_signaling; 1. DR CDD; cd01782; RA1_Afadin; 1. DR CDD; cd01781; RA2_Afadin; 1. DR Gene3D; 2.30.42.10; -; 1. DR Gene3D; 2.60.200.20; -; 1. DR InterPro; IPR028842; Afadin. DR InterPro; IPR037977; CBD_Afadin. DR InterPro; IPR002710; Dilute_dom. DR InterPro; IPR000253; FHA_dom. DR InterPro; IPR001478; PDZ. DR InterPro; IPR036034; PDZ_sf. DR InterPro; IPR000159; RA_dom. DR InterPro; IPR008984; SMAD_FHA_dom_sf. DR InterPro; IPR029071; Ubiquitin-like_domsf. DR PANTHER; PTHR10398; AFADIN; 1. DR PANTHER; PTHR10398:SF2; AFADIN; 1. DR Pfam; PF01843; DIL; 1. DR Pfam; PF00498; FHA; 1. DR Pfam; PF00595; PDZ; 1. DR Pfam; PF00788; RA; 2. DR SMART; SM01132; DIL; 1. DR SMART; SM00240; FHA; 1. DR SMART; SM00228; PDZ; 1. DR SMART; SM00314; RA; 2. DR SUPFAM; SSF50156; PDZ domain-like; 1. DR SUPFAM; SSF49879; SMAD/FHA domain; 1. DR SUPFAM; SSF54236; Ubiquitin-like; 2. DR PROSITE; PS51126; DILUTE; 1. DR PROSITE; PS50106; PDZ; 1. DR PROSITE; PS50200; RA; 2. DR Genevisible; P55196; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Cell adhesion; KW Cell junction; Chromosomal rearrangement; Coiled coil; Phosphoprotein; KW Proto-oncogene; Reference proteome; Repeat. FT CHAIN 1..1824 FT /note="Afadin" FT /id="PRO_0000215918" FT DOMAIN 39..133 FT /note="Ras-associating 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00166" FT DOMAIN 246..348 FT /note="Ras-associating 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00166" FT DOMAIN 426..492 FT /note="FHA" FT DOMAIN 668..908 FT /note="Dilute" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00503" FT DOMAIN 1007..1093 FT /note="PDZ" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143" FT REGION 128..194 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 349..378 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 534..595 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1107..1223 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1235..1473 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1501..1528 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1569..1824 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 146..185 FT /evidence="ECO:0000255" FT COILED 1408..1448 FT /evidence="ECO:0000255" FT COILED 1523..1667 FT /evidence="ECO:0000255" FT COMPBIAS 143..194 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 349..369 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 544..568 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1129..1145 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1154..1169 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1171..1209 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1274..1300 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1302..1340 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1360..1375 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1406..1442 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1443..1473 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1514..1528 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1590..1676 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1682..1711 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1762..1776 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1777..1808 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1809..1824 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 26 FT /note="Breakpoint for translocation to form KMT2A/MLL1- FT AFDN" FT MOD_RES 216 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 246 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 256 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 391 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O35889" FT MOD_RES 424 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 512 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 557 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 562 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 589 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 655 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1083 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1107 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1126 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9QZQ1" FT MOD_RES 1140 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O35889" FT MOD_RES 1143 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1172 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9QZQ1" FT MOD_RES 1173 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1182 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:15144186, FT ECO:0007744|PubMed:17693683, ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 1199 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1211 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 1232 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1238 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1275 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1328 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1330 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1501 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1512 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1696 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 1721 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1774 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9QZQ1" FT MOD_RES 1779 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231" FT MOD_RES 1799 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:24275569" FT MOD_RES 1807 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q9QZQ1" FT VAR_SEQ 139 FT /note="Missing (in isoform 1, isoform 2, isoform 3 and FT isoform 5)" FT /evidence="ECO:0000303|PubMed:17974005, FT ECO:0000303|PubMed:8242616" FT /id="VSP_038707" FT VAR_SEQ 393..407 FT /note="Missing (in isoform 1, isoform 2 and isoform 3)" FT /evidence="ECO:0000303|PubMed:8242616" FT /id="VSP_038708" FT VAR_SEQ 1048 FT /note="Missing (in isoform 2 and isoform 3)" FT /evidence="ECO:0000305" FT /id="VSP_038709" FT VAR_SEQ 1604 FT /note="R -> RTAMPAISVLDL (in isoform 5)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_019257" FT VAR_SEQ 1605..1628 FT /note="LQDEERRRQQQLEEMRKREAEDRA -> VKGGVLWLCPSVVPILASACFPWG FT (in isoform 1)" FT /evidence="ECO:0000303|PubMed:8242616" FT /id="VSP_000217" FT VAR_SEQ 1605..1606 FT /note="Missing (in isoform 6)" FT /evidence="ECO:0000303|Ref.5" FT /id="VSP_041197" FT VAR_SEQ 1629..1824 FT /note="Missing (in isoform 1)" FT /evidence="ECO:0000303|PubMed:8242616" FT /id="VSP_000218" FT VAR_SEQ 1650..1653 FT /note="RRQE -> VMVL (in isoform 6)" FT /evidence="ECO:0000303|Ref.5" FT /id="VSP_041198" FT VAR_SEQ 1654..1824 FT /note="Missing (in isoform 6)" FT /evidence="ECO:0000303|Ref.5" FT /id="VSP_041199" FT VAR_SEQ 1683..1746 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000305" FT /id="VSP_038710" FT VAR_SEQ 1747..1824 FT /note="PNSYPGSTGAAVGAHDACRDAKEKRSKSQDADSPGSSGAPENLTFKERQRLF FT SQGQDVSNKVKASRKLTELENELNTK -> QDKYSSTRKSHGDLLPAPLKPRPPPCQPR FT PASDGVFLSNSFQPPSAKANSTAHKKGQPLPPPKKSSSYHPSHCKGRGKRVTNQLSLS FT (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_038711" FT CONFLICT 374 FT /note="G -> V (in Ref. 1; AAC50059)" FT /evidence="ECO:0000305" FT CONFLICT 1425 FT /note="R -> P (in Ref. 1; AAC50059)" FT /evidence="ECO:0000305" FT STRAND 1007..1013 FT /evidence="ECO:0007829|PDB:7QCR" FT STRAND 1015..1017 FT /evidence="ECO:0007829|PDB:1T2M" FT STRAND 1020..1025 FT /evidence="ECO:0007829|PDB:7QCR" FT STRAND 1028..1031 FT /evidence="ECO:0007829|PDB:1XZ9" FT STRAND 1034..1040 FT /evidence="ECO:0007829|PDB:7QCR" FT STRAND 1042..1044 FT /evidence="ECO:0007829|PDB:1XZ9" FT HELIX 1045..1049 FT /evidence="ECO:0007829|PDB:7QCR" FT STRAND 1057..1061 FT /evidence="ECO:0007829|PDB:7QCR" FT HELIX 1071..1079 FT /evidence="ECO:0007829|PDB:7QCR" FT STRAND 1083..1090 FT /evidence="ECO:0007829|PDB:7QCR" FT TURN 1722..1724 FT /evidence="ECO:0007829|PDB:5A6C" FT TURN 1735..1738 FT /evidence="ECO:0007829|PDB:5A6C" FT CONFLICT P55196-2:1031..1032 FT /note="DV -> D (in Ref. 1; AAC50059 and 2; BAA32485)" FT /evidence="ECO:0000305" SQ SEQUENCE 1824 AA; 206804 MW; 51486232F183A3BA CRC64; MSAGGRDEER RKLADIIHHW NANRLDLFEI SQPTEDLEFH GVMRFYFQDK AAGNFATKCI RVSSTATTQD VIETLAEKFR PDMRMLSSPK YSLYEVHVSG ERRLDIDEKP LVVQLNWNKD DREGRFVLKN ENDAIPPKKA QSNGPEKQEK EGVIQNFKRT LSKKEKKEKK KREKEALRQA SDKDDRPFQG EDVENSRLAA EVYKDMPETS FTRTISNPEV VMKRRRQQKL EKRMQEFRSS DGRPDSGGTL RIYADSLKPN IPYKTILLST TDPADFAVAE ALEKYGLEKE NPKDYCIARV MLPPGAQHSD EKGAKEIILD DDECPLQIFR EWPSDKGILV FQLKRRPPDH IPKKTKKHLE GKTPKGKERA DGSGYGSTLP PEKLPYLVEL SPGRRNHFAY YNYHTYEDGS DSRDKPKLYR LQLSVTEVGT EKLDDNSIQL FGPGIQPHHC DLTNMDGVVT VTPRSMDAET YVEGQRISET TMLQSGMKVQ FGASHVFKFV DPSQDHALAK RSVDGGLMVK GPRHKPGIVQ ETTFDLGGDI HSGTALPTSK STTRLDSDRV SSASSTAERG MVKPMIRVEQ QPDYRRQESR TQDASGPELI LPASIEFRES SEDSFLSAII NYTNSSTVHF KLSPTYVLYM ACRYVLSNQY RPDISPTERT HKVIAVVNKM VSMMEGVIQK QKNIAGALAF WMANASELLN FIKQDRDLSR ITLDAQDVLA HLVQMAFKYL VHCLQSELNN YMPAFLDDPE ENSLQRPKID DVLHTLTGAM SLLRRCRVNA ALTIQLFSQL FHFINMWLFN RLVTDPDSGL CSHYWGAIIR QQLGHIEAWA EKQGLELAAD CHLSRIVQAT TLLTMDKYAP DDIPNINSTC FKLNSLQLQA LLQNYHCAPD EPFIPTDLIE NVVTVAENTA DELARSDGRE VQLEEDPDLQ LPFLLPEDGY SCDVVRNIPN GLQEFLDPLC QRGFCRLIPH TRSPGTWTIY FEGADYESHL LRENTELAQP LRKEPEIITV TLKKQNGMGL SIVAAKGAGQ DKLGIYVKSV VKGGAADVDG RLAAGDQLLS VDGRSLVGLS QERAAELMTR TSSVVTLEVA KQGAIYHGLA TLLNQPSPMM QRISDRRGSG KPRPKSEGFE LYNNSTQNGS PESPQLPWAE YSEPKKLPGD DRLMKNRADH RSSPNVANQP PSPGGKSAYA SGTTAKITSV STGNLCTEEQ TPPPRPEAYP IPTQTYTREY FTFPASKSQD RMAPPQNQWP NYEEKPHMHT DSNHSSIAIQ RVTRSQEELR EDKAYQLERH RIEAAMDRKS DSDMWINQSS SLDSSTSSQE HLNHSSKSVT PASTLTKSGP GRWKTPAAIP ATPVAVSQPI RTDLPPPPPP PPVHYAGDFD GMSMDLPLPP PPSANQIGLP SAQVAAAERR KREEHQRWYE KEKARLEEER ERKRREQERK LGQMRTQSLN PAPFSPLTAQ QMKPEKPSTL QRPQETVIRE LQPQQQPRTI ERRDLQYITV SKEELSSGDS LSPDPWKRDA KEKLEKQQQM HIVDMLSKEI QELQSKPDRS AEESDRLRKL MLEWQFQKRL QESKQKDEDD EEEEDDDVDT MLIMQRLEAE RRARLQDEER RRQQQLEEMR KREAEDRARQ EEERRRQEEE RTKRDAEEKR RQEEGYYSRL EAERRRQHDE AARRLLEPEA PGLCRPPLPR DYEPPSPSPA PGAPPPPPQR NASYLKTQVL SPDSLFTAKF VAYNEEEEEE DCSLAGPNSY PGSTGAAVGA HDACRDAKEK RSKSQDADSP GSSGAPENLT FKERQRLFSQ GQDVSNKVKA SRKLTELENE LNTK //