AFAD_HUMAN
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 03-AUG-2022, entry version 220.
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="http://atlasgeneticsoncology.org/Genes/AF6ID6.html";
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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 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 PDBsum; 1T2M; -.
DR PDBsum; 1XZ9; -.
DR PDBsum; 2AIN; -.
DR PDBsum; 2EXG; -.
DR PDBsum; 5A6C; -.
DR AlphaFoldDB; P55196; -.
DR BMRB; P55196; -.
DR SMR; P55196; -.
DR BioGRID; 110447; 286.
DR CORUM; P55196; -.
DR ELM; P55196; -.
DR IntAct; P55196; 54.
DR MINT; P55196; -.
DR STRING; 9606.ENSP00000375960; -.
DR DrugBank; DB08574; (5R)-2-sulfanyl-5-[4-(trifluoromethyl)benzyl]-1,3-thiazol-4(5H)-one.
DR GlyGen; P55196; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P55196; -.
DR PhosphoSitePlus; P55196; -.
DR BioMuta; AFDN; -.
DR DMDM; 288558835; -.
DR EPD; P55196; -.
DR jPOST; P55196; -.
DR MassIVE; P55196; -.
DR MaxQB; P55196; -.
DR PaxDb; P55196; -.
DR PeptideAtlas; P55196; -.
DR PRIDE; 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 Antibodypedia; 4608; 279 antibodies from 32 providers.
DR DNASU; 4301; -.
DR Ensembl; ENST00000392108.7; ENSP00000375956.3; ENSG00000130396.21. [P55196-6]
DR Ensembl; ENST00000392112.5; ENSP00000375960.2; ENSG00000130396.21. [P55196-3]
DR Ensembl; ENST00000400822.7; ENSP00000383623.3; ENSG00000130396.21. [P55196-5]
DR Ensembl; ENST00000447894.6; ENSP00000404595.2; ENSG00000130396.21. [P55196-4]
DR GeneID; 4301; -.
DR KEGG; hsa:4301; -.
DR UCSC; uc003qwc.3; human. [P55196-4]
DR CTD; 4301; -.
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; 23029at2759; -.
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; 32 hits in 1084 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 179 other tissues.
DR ExpressionAtlas; P55196; baseline and differential.
DR Genevisible; P55196; HS.
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:0008022; F:protein C-terminus binding; TAS:ProtInc.
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:0043547; P:positive regulation of GTPase activity; 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; cd00060; FHA; 1.
DR CDD; cd15471; Myo5p-like_CBD_afadin; 1.
DR Gene3D; 2.30.42.10; -; 1.
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 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; SSF49879; SSF49879; 1.
DR SUPFAM; SSF50156; SSF50156; 1.
DR SUPFAM; SSF54236; SSF54236; 2.
DR PROSITE; PS51126; DILUTE; 1.
DR PROSITE; PS50106; PDZ; 1.
DR PROSITE; PS50200; RA; 2.
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 1006..1013
FT /evidence="ECO:0007829|PDB:1T2M"
FT STRAND 1015..1017
FT /evidence="ECO:0007829|PDB:1T2M"
FT STRAND 1020..1025
FT /evidence="ECO:0007829|PDB:1T2M"
FT STRAND 1028..1031
FT /evidence="ECO:0007829|PDB:1XZ9"
FT STRAND 1034..1040
FT /evidence="ECO:0007829|PDB:1T2M"
FT STRAND 1042..1044
FT /evidence="ECO:0007829|PDB:1XZ9"
FT HELIX 1045..1049
FT /evidence="ECO:0007829|PDB:1T2M"
FT STRAND 1054..1061
FT /evidence="ECO:0007829|PDB:1T2M"
FT HELIX 1071..1079
FT /evidence="ECO:0007829|PDB:1T2M"
FT STRAND 1083..1091
FT /evidence="ECO:0007829|PDB:1T2M"
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
