EEA1_HUMAN
ID EEA1_HUMAN Reviewed; 1411 AA.
AC Q15075; Q14221;
DT 22-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 05-MAY-2009, sequence version 2.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Early endosome antigen 1;
DE AltName: Full=Endosome-associated protein p162;
DE AltName: Full=Zinc finger FYVE domain-containing protein 2;
GN Name=EEA1; Synonyms=ZFYVE2;
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], SUBCELLULAR LOCATION, AND VARIANT GLN-810.
RC TISSUE=Cervix carcinoma;
RX PubMed=7768953; DOI=10.1074/jbc.270.22.13503;
RA Mu F.-T., Callaghan J.M., Steele-Mortimer O., Stenmark H., Parton R.G.,
RA Campbell P.L., McCluskey J., Yeo J.-P., Tock E.P.C., Toh B.-H.;
RT "EEA1, an early endosome-associated protein. EEA1 is a conserved alpha-
RT helical peripheral membrane protein flanked by cysteine 'fingers' and
RT contains a calmodulin-binding IQ motif.";
RL J. Biol. Chem. 270:13503-13511(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT GLN-810.
RA Seelig H.P.;
RL Submitted (APR-1994) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [4]
RP PROTEIN SEQUENCE OF 996-1011 AND 1319-1332, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC TISSUE=Fetal brain cortex;
RA Lubec G., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [5]
RP INTERACTION WITH RAB5A.
RX PubMed=9697774; DOI=10.1038/28879;
RA Simonsen A., Lippe R., Christoforidis S., Gaullier J.-M., Brech A.,
RA Callaghan J.M., Toh B.-H., Murphy C., Zerial M., Stenmark H.;
RT "EEA1 links PI(3)K function to Rab5 regulation of endosome fusion.";
RL Nature 394:494-498(1998).
RN [6]
RP INTERACTION WITH RAB5A AND RAB5B.
RX PubMed=10491193; DOI=10.1046/j.1432-1327.1999.00743.x;
RA Callaghan J.M., Nixon S., Bucci C., Toh B.-H., Stenmark H.;
RT "Direct interaction of EEA1 with Rab5b.";
RL Eur. J. Biochem. 265:361-366(1999).
RN [7]
RP INTERACTION WITH STX6, AND SUBCELLULAR LOCATION.
RX PubMed=10506127; DOI=10.1074/jbc.274.41.28857;
RA Simonsen A., Gaullier J.-M., D'Arrigo A., Stenmark H.;
RT "The Rab5 effector EEA1 interacts directly with syntaxin-6.";
RL J. Biol. Chem. 274:28857-28860(1999).
RN [8]
RP MUTAGENESIS OF ASP-1352; ASN-1357; 1367-VAL-THR-1368; ARG-1375 AND
RP ARG-1400, HOMODIMERIZATION, AND INTERACTION WITH PHOSPHATIDYLINOSITOL
RP 3-PHOSPHATE.
RX PubMed=10394369; DOI=10.1016/s1097-2765(01)80013-7;
RA Kutateladze T.G., Ogburn K.D., Watson W.T., de Beer T., Emr S.D.,
RA Burd C.G., Overduin M.;
RT "Phosphatidylinositol 3-phosphate recognition by the FYVE domain.";
RL Mol. Cell 3:805-811(1999).
RN [9]
RP MUTAGENESIS OF TRP-1349; CYS-1358; PHE-1365; ARG-1370; ARG-1371; HIS-1372;
RP HIS-1373; CYS-1374; ARG-1375; CYS-1377; GLY-1378; CYS-1385; ARG-1400 AND
RP CYS-1405, SUBCELLULAR LOCATION, AND INTERACTION WITH PHOSPHATIDYLINOSITOL
RP 3-PHOSPHATE.
RX PubMed=10807926; DOI=10.1074/jbc.m906554199;
RA Gaullier J.-M., Roenning E., Gillooly D.J., Stenmark H.;
RT "Interaction of the EEA1 FYVE finger with phosphatidylinositol 3-phosphate
RT and early endosomes. Role of conserved residues.";
RL J. Biol. Chem. 275:24595-24600(2000).
RN [10]
RP INTERACTION WITH RAB22A.
RX PubMed=11870209; DOI=10.1242/jcs.115.5.899;
RA Kauppi M., Simonsen A., Bremnes B., Vieira A., Callaghan J.M., Stenmark H.,
RA Olkkonen V.M.;
RT "The small GTPase Rab22 interacts with EEA1 and controls endosomal membrane
RT trafficking.";
RL J. Cell Sci. 115:899-911(2002).
RN [11]
RP MUTAGENESIS OF GLU-39; PHE-41; ILE-42; PRO-44; MET-47 AND TYR-60,
RP HOMODIMERIZATION, AND INTERACTION WITH RAB5C.
RX PubMed=12493736; DOI=10.1074/jbc.m211514200;
RA Merithew E., Stone C., Eathiraj S., Lambright D.G.;
RT "Determinants of Rab5 interaction with the N-terminus of early endosome
RT antigen 1.";
RL J. Biol. Chem. 278:8494-8500(2003).
RN [12]
RP INTERACTION WITH ERBB2.
RX PubMed=16314522; DOI=10.1128/mcb.25.24.11005-11018.2005;
RA Giri D.K., Ali-Seyed M., Li L.Y., Lee D.F., Ling P., Bartholomeusz G.,
RA Wang S.C., Hung M.C.;
RT "Endosomal transport of ErbB-2: mechanism for nuclear entry of the cell
RT surface receptor.";
RL Mol. Cell. Biol. 25:11005-11018(2005).
RN [13]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH RAB31.
RX PubMed=19725050; DOI=10.1002/jcp.21911;
RA Ng E.L., Ng J.J., Liang F., Tang B.L.;
RT "Rab22B is expressed in the CNS astroglia lineage and plays a role in
RT epidermal growth factor receptor trafficking in A431 cells.";
RL J. Cell. Physiol. 221:716-728(2009).
RN [14]
RP DOMAIN FYVE-TYPE ZINC-FINGER, AND MUTAGENESIS OF HIS-1372 AND HIS-1373.
RX PubMed=19296456; DOI=10.1002/prot.22392;
RA He J., Vora M., Haney R.M., Filonov G.S., Musselman C.A., Burd C.G.,
RA Kutateladze A.G., Verkhusha V.V., Stahelin R.V., Kutateladze T.G.;
RT "Membrane insertion of the FYVE domain is modulated by pH.";
RL Proteins 76:852-860(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-70, AND IDENTIFICATION BY
RP 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 INTERACTION WITH PLEKHF2, AND SUBCELLULAR LOCATION.
RX PubMed=22816767; DOI=10.1111/j.1600-0854.2012.01400.x;
RA Pedersen N.M., Raiborg C., Brech A., Skarpen E., Roxrud I., Platta H.W.,
RA Liestol K., Stenmark H.;
RT "The PtdIns3P-binding protein Phafin 2 mediates epidermal growth factor
RT receptor degradation by promoting endosome fusion.";
RL Traffic 13:1547-1563(2012).
RN [18]
RP INTERACTION WITH SAMD9 AND SAMD9L.
RX PubMed=24029230; DOI=10.1016/j.ccr.2013.08.011;
RA Nagamachi A., Matsui H., Asou H., Ozaki Y., Aki D., Kanai A., Takubo K.,
RA Suda T., Nakamura T., Wolff L., Honda H., Inaba T.;
RT "Haploinsufficiency of SAMD9L, an endosome fusion facilitator, causes
RT myeloid malignancies in mice mimicking human diseases with monosomy 7.";
RL Cancer Cell 24:305-317(2013).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-52 AND SER-70, AND
RP IDENTIFICATION BY MASS 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 [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE 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 [21]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1289-1411 IN COMPLEX WITH
RP PHOSPHATIDYLINOSITOL 3-PHOSPHATE, AND HOMODIMERIZATION.
RX PubMed=11741531; DOI=10.1016/s1097-2765(01)00385-9;
RA Dumas J.J., Merithew E., Sudharshan E., Rajamani D., Hayes S., Lawe D.,
RA Corvera S., Lambright D.G.;
RT "Multivalent endosome targeting by homodimeric EEA1.";
RL Mol. Cell 8:947-958(2001).
RN [22]
RP STRUCTURE BY NMR OF 1346-1410 ALONE AND IN COMPLEX WITH
RP PHOSPHATIDYLINOSITOL 3-PHOSPHATE.
RX PubMed=11230696; DOI=10.1126/science.291.5509.1793;
RA Kutateladze T.G., Overduin M.;
RT "Structural mechanism of endosome docking by the FYVE domain.";
RL Science 291:1793-1796(2001).
CC -!- FUNCTION: Binds phospholipid vesicles containing phosphatidylinositol
CC 3-phosphate and participates in endosomal trafficking.
CC -!- SUBUNIT: Homodimer. Binds STX6. Binds RAB5A, RAB5B, RAB5C and RAB22A
CC that have been activated by GTP-binding. Interacts with RAB31.
CC Interacts with ERBB2. Interacts with SAMD9 AND SAMD9L
CC (PubMed:24029230). May interact with PLEKHF2.
CC {ECO:0000269|PubMed:10394369, ECO:0000269|PubMed:10491193,
CC ECO:0000269|PubMed:10506127, ECO:0000269|PubMed:10807926,
CC ECO:0000269|PubMed:11230696, ECO:0000269|PubMed:11741531,
CC ECO:0000269|PubMed:11870209, ECO:0000269|PubMed:12493736,
CC ECO:0000269|PubMed:16314522, ECO:0000269|PubMed:19725050,
CC ECO:0000269|PubMed:22816767, ECO:0000269|PubMed:24029230,
CC ECO:0000269|PubMed:9697774}.
CC -!- INTERACTION:
CC Q15075; P04626: ERBB2; NbExp=5; IntAct=EBI-298113, EBI-641062;
CC Q15075; Q9UL26: RAB22A; NbExp=3; IntAct=EBI-298113, EBI-399456;
CC Q15075; P20339: RAB5A; NbExp=4; IntAct=EBI-298113, EBI-399437;
CC Q15075; P61020: RAB5B; NbExp=3; IntAct=EBI-298113, EBI-399401;
CC Q15075; P51148: RAB5C; NbExp=3; IntAct=EBI-298113, EBI-1054923;
CC Q15075; Q5K651: SAMD9; NbExp=2; IntAct=EBI-298113, EBI-2814750;
CC Q15075; Q7Z3T8: ZFYVE16; NbExp=4; IntAct=EBI-298113, EBI-298055;
CC Q15075; Q69Z37: Samd9l; Xeno; NbExp=2; IntAct=EBI-298113, EBI-8784283;
CC Q15075; Q63635: Stx6; Xeno; NbExp=4; IntAct=EBI-298113, EBI-398854;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Early endosome membrane; Peripheral
CC membrane protein.
CC -!- DOMAIN: The FYVE-type zinc finger domain mediates interactions with
CC phosphatidylinositol 3-phosphate in membranes of early endosomes and
CC penetrates bilayers. The FYVE domain insertion into PtdIns(3)P-enriched
CC membranes is substantially increased in acidic conditions.
CC {ECO:0000269|PubMed:19296456}.
CC -!- MISCELLANEOUS: Antibodies against EEA1 are found in sera from patients
CC with subacute cutaneous lupus erythematosus and other autoimmune
CC diseases.
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DR EMBL; L40157; AAA79121.1; -; mRNA.
DR EMBL; X78998; CAA55632.1; -; mRNA.
DR EMBL; AC016136; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC021646; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC026111; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS31874.1; -.
DR PIR; A57013; A57013.
DR RefSeq; NP_003557.2; NM_003566.3.
DR PDB; 1HYI; NMR; -; A=1347-1411.
DR PDB; 1HYJ; NMR; -; A=1347-1411.
DR PDB; 1JOC; X-ray; 2.20 A; A/B=1287-1324, A/B=1326-1411.
DR PDB; 3MJH; X-ray; 2.03 A; B/D=36-69.
DR PDBsum; 1HYI; -.
DR PDBsum; 1HYJ; -.
DR PDBsum; 1JOC; -.
DR PDBsum; 3MJH; -.
DR AlphaFoldDB; Q15075; -.
DR BMRB; Q15075; -.
DR SMR; Q15075; -.
DR BioGRID; 113999; 130.
DR CORUM; Q15075; -.
DR IntAct; Q15075; 102.
DR MINT; Q15075; -.
DR STRING; 9606.ENSP00000317955; -.
DR DrugBank; DB02942; Inositol 1,3-Bisphosphate.
DR iPTMnet; Q15075; -.
DR MetOSite; Q15075; -.
DR PhosphoSitePlus; Q15075; -.
DR SwissPalm; Q15075; -.
DR BioMuta; EEA1; -.
DR DMDM; 229462866; -.
DR EPD; Q15075; -.
DR jPOST; Q15075; -.
DR MassIVE; Q15075; -.
DR MaxQB; Q15075; -.
DR PaxDb; Q15075; -.
DR PeptideAtlas; Q15075; -.
DR PRIDE; Q15075; -.
DR ProteomicsDB; 60427; -.
DR Antibodypedia; 3127; 534 antibodies from 44 providers.
DR DNASU; 8411; -.
DR Ensembl; ENST00000322349.13; ENSP00000317955.8; ENSG00000102189.17.
DR GeneID; 8411; -.
DR KEGG; hsa:8411; -.
DR MANE-Select; ENST00000322349.13; ENSP00000317955.8; NM_003566.4; NP_003557.3.
DR UCSC; uc001tck.4; human.
DR CTD; 8411; -.
DR DisGeNET; 8411; -.
DR GeneCards; EEA1; -.
DR HGNC; HGNC:3185; EEA1.
DR HPA; ENSG00000102189; Low tissue specificity.
DR MIM; 605070; gene.
DR neXtProt; NX_Q15075; -.
DR OpenTargets; ENSG00000102189; -.
DR PharmGKB; PA27621; -.
DR VEuPathDB; HostDB:ENSG00000102189; -.
DR eggNOG; ENOG502QWB5; Eukaryota.
DR GeneTree; ENSGT00940000156910; -.
DR HOGENOM; CLU_256550_0_0_1; -.
DR InParanoid; Q15075; -.
DR OMA; FIAVYQH; -.
DR OrthoDB; 753155at2759; -.
DR PhylomeDB; Q15075; -.
DR TreeFam; TF329698; -.
DR PathwayCommons; Q15075; -.
DR Reactome; R-HSA-168138; Toll Like Receptor 9 (TLR9) Cascade.
DR SignaLink; Q15075; -.
DR SIGNOR; Q15075; -.
DR BioGRID-ORCS; 8411; 16 hits in 1078 CRISPR screens.
DR ChiTaRS; EEA1; human.
DR EvolutionaryTrace; Q15075; -.
DR GeneWiki; EEA1; -.
DR GenomeRNAi; 8411; -.
DR Pharos; Q15075; Tbio.
DR PRO; PR:Q15075; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q15075; protein.
DR Bgee; ENSG00000102189; Expressed in calcaneal tendon and 196 other tissues.
DR ExpressionAtlas; Q15075; baseline and differential.
DR Genevisible; Q15075; HS.
DR GO; GO:0044308; C:axonal spine; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005769; C:early endosome; IDA:UniProtKB.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0019897; C:extrinsic component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; TAS:ProtInc.
DR GO; GO:0005969; C:serine-pyruvate aminotransferase complex; IEA:Ensembl.
DR GO; GO:0005545; F:1-phosphatidylinositol binding; IDA:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; NAS:UniProtKB.
DR GO; GO:0030742; F:GTP-dependent protein binding; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; TAS:UniProtKB.
DR GO; GO:0045022; P:early endosome to late endosome transport; NAS:UniProtKB.
DR GO; GO:0006897; P:endocytosis; IMP:UniProtKB.
DR GO; GO:0044788; P:modulation by host of viral process; IMP:ParkinsonsUK-UCL.
DR GO; GO:0016189; P:synaptic vesicle to endosome fusion; TAS:UniProtKB.
DR GO; GO:0006906; P:vesicle fusion; IMP:UniProtKB.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR013087; Znf_C2H2_type.
DR InterPro; IPR000306; Znf_FYVE.
DR InterPro; IPR017455; Znf_FYVE-rel.
DR InterPro; IPR011011; Znf_FYVE_PHD.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR Pfam; PF01363; FYVE; 1.
DR SMART; SM00064; FYVE; 1.
DR SUPFAM; SSF57903; SSF57903; 1.
DR PROSITE; PS50178; ZF_FYVE; 1.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 1.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Coiled coil; Cytoplasm; Direct protein sequencing; Endosome;
KW Membrane; Metal-binding; Phosphoprotein; Reference proteome; Zinc;
KW Zinc-finger.
FT CHAIN 1..1411
FT /note="Early endosome antigen 1"
FT /id="PRO_0000098706"
FT ZN_FING 41..64
FT /note="C2H2-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 1352..1410
FT /note="FYVE-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT REGION 1..27
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 473..501
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 74..1348
FT /evidence="ECO:0000255"
FT COMPBIAS 11..27
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 473..488
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 1358
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 1361
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 1374
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 1377
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 1382
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 1385
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 1402
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 1405
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT MOD_RES 52
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 70
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT VARIANT 810
FT /note="K -> Q (in dbSNP:rs10745623)"
FT /evidence="ECO:0000269|PubMed:7768953, ECO:0000269|Ref.2"
FT /id="VAR_052980"
FT MUTAGEN 39
FT /note="E->A: Strongly reduces interaction with RAB5C."
FT /evidence="ECO:0000269|PubMed:12493736"
FT MUTAGEN 41
FT /note="F->A: Strongly reduces interaction with RAB5C."
FT /evidence="ECO:0000269|PubMed:12493736"
FT MUTAGEN 42
FT /note="I->A: Strongly reduces interaction with RAB5C."
FT /evidence="ECO:0000269|PubMed:12493736"
FT MUTAGEN 44
FT /note="P->A: Strongly reduces interaction with RAB5C."
FT /evidence="ECO:0000269|PubMed:12493736"
FT MUTAGEN 47
FT /note="M->A: Strongly reduces interaction with RAB5C."
FT /evidence="ECO:0000269|PubMed:12493736"
FT MUTAGEN 60
FT /note="Y->A: Strongly reduces interaction with RAB5C."
FT /evidence="ECO:0000269|PubMed:12493736"
FT MUTAGEN 1349
FT /note="W->A: Reduces phosphatidylinositol 3-phosphate
FT binding and endosomal location."
FT /evidence="ECO:0000269|PubMed:10807926"
FT MUTAGEN 1352
FT /note="D->V: Reduces phosphatidylinositol 3-phosphate
FT binding and endosomal location."
FT /evidence="ECO:0000269|PubMed:10394369"
FT MUTAGEN 1357
FT /note="N->D: Reduces phosphatidylinositol 3-phosphate
FT binding and endosomal location."
FT /evidence="ECO:0000269|PubMed:10394369"
FT MUTAGEN 1358
FT /note="C->S: Abolishes phosphatidylinositol 3-phosphate
FT binding and endosomal location."
FT /evidence="ECO:0000269|PubMed:10807926"
FT MUTAGEN 1365
FT /note="F->A: Strongly reduces phosphatidylinositol 3-
FT phosphate binding and endosomal location."
FT /evidence="ECO:0000269|PubMed:10807926"
FT MUTAGEN 1367..1368
FT /note="VT->EE,GG: Abolishes phosphatidylinositol 3-
FT phosphate binding and endosomal location."
FT /evidence="ECO:0000269|PubMed:10394369"
FT MUTAGEN 1370
FT /note="R->A: Abolishes endosomal location."
FT /evidence="ECO:0000269|PubMed:10807926"
FT MUTAGEN 1371
FT /note="R->A: Abolishes phosphatidylinositol 3-phosphate
FT binding and endosomal location."
FT /evidence="ECO:0000269|PubMed:10807926"
FT MUTAGEN 1372
FT /note="H->A: Abolishes endosomal location. Abolishes pH
FT sensitivity of the FYVE-type zinc finger domain; when
FT associated with A-1373."
FT /evidence="ECO:0000269|PubMed:10807926,
FT ECO:0000269|PubMed:19296456"
FT MUTAGEN 1373
FT /note="H->A: Abolishes phosphatidylinositol 3-phosphate
FT binding and endosomal location. Abolishes pH sensitivity of
FT the FYVE-type zinc finger domain; when associated with A-
FT 1372."
FT /evidence="ECO:0000269|PubMed:10807926,
FT ECO:0000269|PubMed:19296456"
FT MUTAGEN 1374
FT /note="C->A: Abolishes phosphatidylinositol 3-phosphate
FT binding and endosomal location."
FT /evidence="ECO:0000269|PubMed:10807926"
FT MUTAGEN 1375
FT /note="R->G: Abolishes phosphatidylinositol 3-phosphate
FT binding and endosomal location."
FT /evidence="ECO:0000269|PubMed:10394369,
FT ECO:0000269|PubMed:10807926"
FT MUTAGEN 1377
FT /note="C->A: Abolishes phosphatidylinositol 3-phosphate
FT binding and endosomal location."
FT /evidence="ECO:0000269|PubMed:10807926"
FT MUTAGEN 1378
FT /note="G->A: Abolishes phosphatidylinositol 3-phosphate
FT binding and endosomal location."
FT /evidence="ECO:0000269|PubMed:10807926"
FT MUTAGEN 1385
FT /note="C->A: Abolishes phosphatidylinositol 3-phosphate
FT binding and endosomal location."
FT /evidence="ECO:0000269|PubMed:10807926"
FT MUTAGEN 1400
FT /note="R->G: Strongly reduces phosphatidylinositol 3-
FT phosphate binding and abolishes endosomal location."
FT /evidence="ECO:0000269|PubMed:10394369,
FT ECO:0000269|PubMed:10807926"
FT MUTAGEN 1405
FT /note="C->S: Abolishes phosphatidylinositol 3-phosphate
FT binding and endosomal location."
FT /evidence="ECO:0000269|PubMed:10807926"
FT CONFLICT 255
FT /note="C -> S (in Ref. 1; AAA79121)"
FT /evidence="ECO:0000305"
FT CONFLICT 258..259
FT /note="LQ -> FE (in Ref. 1; AAA79121)"
FT /evidence="ECO:0000305"
FT CONFLICT 277
FT /note="A -> S (in Ref. 1; AAA79121)"
FT /evidence="ECO:0000305"
FT CONFLICT 284
FT /note="A -> R (in Ref. 1; AAA79121)"
FT /evidence="ECO:0000305"
FT CONFLICT 520
FT /note="D -> E (in Ref. 1; AAA79121)"
FT /evidence="ECO:0000305"
FT CONFLICT 575..576
FT /note="EQ -> DE (in Ref. 1; AAA79121)"
FT /evidence="ECO:0000305"
FT CONFLICT 583..584
FT /note="KL -> NV (in Ref. 1; AAA79121)"
FT /evidence="ECO:0000305"
FT CONFLICT 680
FT /note="Q -> H (in Ref. 1; AAA79121)"
FT /evidence="ECO:0000305"
FT CONFLICT 1325
FT /note="Missing (in Ref. 1; AAA79121)"
FT /evidence="ECO:0000305"
FT STRAND 38..42
FT /evidence="ECO:0007829|PDB:3MJH"
FT TURN 44..46
FT /evidence="ECO:0007829|PDB:3MJH"
FT STRAND 49..52
FT /evidence="ECO:0007829|PDB:3MJH"
FT HELIX 53..63
FT /evidence="ECO:0007829|PDB:3MJH"
FT STRAND 65..67
FT /evidence="ECO:0007829|PDB:3MJH"
FT HELIX 1290..1324
FT /evidence="ECO:0007829|PDB:1JOC"
FT HELIX 1326..1346
FT /evidence="ECO:0007829|PDB:1JOC"
FT HELIX 1352..1354
FT /evidence="ECO:0007829|PDB:1JOC"
FT TURN 1359..1361
FT /evidence="ECO:0007829|PDB:1JOC"
FT STRAND 1367..1369
FT /evidence="ECO:0007829|PDB:1JOC"
FT STRAND 1371..1373
FT /evidence="ECO:0007829|PDB:1HYI"
FT TURN 1375..1377
FT /evidence="ECO:0007829|PDB:1JOC"
FT STRAND 1380..1382
FT /evidence="ECO:0007829|PDB:1HYI"
FT HELIX 1383..1385
FT /evidence="ECO:0007829|PDB:1JOC"
FT STRAND 1388..1390
FT /evidence="ECO:0007829|PDB:1JOC"
FT TURN 1393..1396
FT /evidence="ECO:0007829|PDB:1HYI"
FT STRAND 1399..1401
FT /evidence="ECO:0007829|PDB:1JOC"
FT HELIX 1403..1408
FT /evidence="ECO:0007829|PDB:1JOC"
SQ SEQUENCE 1411 AA; 162466 MW; 51BA418F561E3411 CRC64;
MLRRILQRTP GRVGSQGSDL DSSATPINTV DVNNESSSEG FICPQCMKSL GSADELFKHY
EAVHDAGNDS GHGGESNLAL KRDDVTLLRQ EVQDLQASLK EEKWYSEELK KELEKYQGLQ
QQEAKPDGLV TDSSAELQSL EQQLEEAQTE NFNIKQMKDL FEQKAAQLAT EIADIKSKYD
EERSLREAAE QKVTRLTEEL NKEATVIQDL KTELLQRPGI EDVAVLKKEL VQVQTLMDNM
TLERERESEK LKDECKKLQS QYASSEATIS QLRSELAKGP QEVAVYVQEL QKLKSSVNEL
TQKNQTLTEN LLKKEQDYTK LEEKHNEESV SKKNIQATLH QKDLDCQQLQ SRLSASETSL
HRIHVELSEK GEATQKLKEE LSEVETKYQH LKAEFKQLQQ QREEKEQHGL QLQSEINQLH
SKLLETERQL GEAHGRLKEQ RQLSSEKLMD KEQQVADLQL KLSRLEEQLK EKVTNSTELQ
HQLDKTKQQH QEQQALQQST TAKLREAQND LEQVLRQIGD KDQKIQNLEA LLQKSKENIS
LLEKEREDLY AKIQAGEGET AVLNQLQEKN HTLQEQVTQL TEKLKNQSES HKQAQENLHD
QVQEQKAHLR AAQDRVLSLE TSVNELNSQL NESKEKVSQL DIQIKAKTEL LLSAEAAKTA
QRADLQNHLD TAQNALQDKQ QELNKITTQL DQVTAKLQDK QEHCSQLESH LKEYKEKYLS
LEQKTEELEG QIKKLEADSL EVKASKEQAL QDLQQQRQLN TDLELRATEL SKQLEMEKEI
VSSTRLDLQK KSEALESIKQ KLTKQEEEKK ILKQDFETLS QETKIQHEEL NNRIQTTVTE
LQKVKMEKEA LMTELSTVKD KLSKVSDSLK NSKSEFEKEN QKGKAAILDL EKTCKELKHQ
LQVQMENTLK EQKELKKSLE KEKEASHQLK LELNSMQEQL IQAQNTLKQN EKEEQQLQGN
INELKQSSEQ KKKQIEALQG ELKIAVLQKT ELENKLQQQL TQAAQELAAE KEKISVLQNN
YEKSQETFKQ LQSDFYGRES ELLATRQDLK SVEEKLSLAQ EDLISNRNQI GNQNKLIQEL
KTAKATLEQD SAKKEQQLQE RCKALQDIQK EKSLKEKELV NEKSKLAEIE EIKCRQEKEI
TKLNEELKSH KLESIKEITN LKDAKQLLIQ QKLELQGKAD SLKAAVEQEK RNQQILKDQV
KKEEEELKKE FIEKEAKLHS EIKEKEVGMK KHEENEAKLT MQITALNENL GTVKKEWQSS
QRRVSELEKQ TDDLRGEIAV LEATVQNNQD ERRALLERCL KGEGEIEKLQ TKVLELQRKL
DNTTAAVQEL GRENQSLQIK HTQALNRKWA EDNEVQNCMA CGKGFSVTVR RHHCRQCGNI
FCAECSAKNA LTPSSKKPVR VCDACFNDLQ G
