Full text data of EEA1
EEA1
(ZFYVE2)
[Confidence: low (only semi-automatic identification from reviews)]
Early endosome antigen 1 (Endosome-associated protein p162; Zinc finger FYVE domain-containing protein 2)
Early endosome antigen 1 (Endosome-associated protein p162; Zinc finger FYVE domain-containing protein 2)
UniProt
Q15075
ID EEA1_HUMAN Reviewed; 1411 AA.
AC Q15075; Q14221;
DT 22-AUG-2003, integrated into UniProtKB/Swiss-Prot.
read moreDT 05-MAY-2009, sequence version 2.
DT 22-JAN-2014, entry version 118.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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.,
RA Parton R.G., Campbell P.L., McCluskey J., Yeo J.-P., Tock E.P.C.,
RA Toh B.-H.;
RT "EEA1, an early endosome-associated protein. EEA1 is a conserved
RT alpha-helical peripheral membrane protein flanked by cysteine
RT 'fingers' and 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.,
RA Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D.,
RA Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z.,
RA Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H.,
RA Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H.,
RA Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V.,
RA Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J.,
RA Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A.,
RA Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M.,
RA Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E.,
RA 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.,
RA Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R.,
RA Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J.,
RA Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C.,
RA Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M.,
RA Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M.,
RA Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P.,
RA Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L.,
RA Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E.,
RA Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C.,
RA Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F.,
RA Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M.,
RA Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S.,
RA 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.,
RA Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I.,
RA Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T.,
RA Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S.,
RA Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D.,
RA Kucherlapati R., Weinstock G., 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 MASS 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;
RP HIS-1372; HIS-1373; CYS-1374; ARG-1375; CYS-1377; GLY-1378; CYS-1385;
RP ARG-1400 AND CYS-1405, SUBCELLULAR LOCATION, AND INTERACTION WITH
RP PHOSPHATIDYLINOSITOL 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-
RT phosphate and early endosomes. Role of conserved residues.";
RL J. Biol. Chem. 275:24595-24600(2000).
RN [10]
RP INTERACTION WITH RAB22A.
RX PubMed=11870209;
RA Kauppi M., Simonsen A., Bremnes B., Vieira A., Callaghan J.M.,
RA Stenmark H., Olkkonen V.M.;
RT "The small GTPase Rab22 interacts with EEA1 and controls endosomal
RT membrane 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
RT endosome 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
RT cell 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
RP 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 MASS
RP SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation 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.,
RA Buerckstuemmer T., 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.,
RA Platta H.W., Liestol K., Stenmark H.;
RT "The PtdIns3P-binding protein Phafin 2 mediates epidermal growth
RT factor receptor degradation by promoting endosome fusion.";
RL Traffic 13:1547-1563(2012).
RN [18]
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.,
RA Lawe D., Corvera S., Lambright D.G.;
RT "Multivalent endosome targeting by homodimeric EEA1.";
RL Mol. Cell 8:947-958(2001).
RN [19]
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
CC phosphatidylinositol 3-phosphate and participates in endosomal
CC trafficking.
CC -!- SUBUNIT: Homodimer. Binds STX6. Binds RAB5A, RAB5B, RAB5C and
CC RAB22A that have been activated by GTP-binding. Interacts with
CC RAB31. Interacts with ERBB2. May interact with PLEKHF2.
CC -!- INTERACTION:
CC P04626:ERBB2; NbExp=5; IntAct=EBI-298113, EBI-641062;
CC Q9UL26:RAB22A; NbExp=3; IntAct=EBI-298113, EBI-399456;
CC P20339:RAB5A; NbExp=4; IntAct=EBI-298113, EBI-399437;
CC P61020:RAB5B; NbExp=3; IntAct=EBI-298113, EBI-399401;
CC Q5K651:SAMD9; NbExp=2; IntAct=EBI-298113, EBI-2814750;
CC Q69Z37:Samd9l (xeno); NbExp=2; IntAct=EBI-298113, EBI-8784283;
CC Q63635:Stx6 (xeno); NbExp=4; IntAct=EBI-298113, EBI-398854;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Early endosome membrane;
CC Peripheral membrane protein.
CC -!- DOMAIN: The FYVE-type zinc finger domain mediates interactions
CC with phosphatidylinositol 3-phosphate in membranes of early
CC endosomes and penetrates bilayers. The FYVE domain insertion into
CC PtdIns(3)P-enriched membranes is substantially increased in acidic
CC conditions.
CC -!- MISCELLANEOUS: Antibodies against EEA1 are found in sera from
CC patients with subacute cutaneous lupus erythematosus and other
CC autoimmune diseases.
CC -!- SIMILARITY: Contains 1 C2H2-type zinc finger.
CC -!- SIMILARITY: Contains 1 FYVE-type zinc finger.
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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 PIR; A57013; A57013.
DR RefSeq; NP_003557.2; NM_003566.3.
DR UniGene; Hs.567367; -.
DR PDB; 1HYI; NMR; -; A=1347-1411.
DR PDB; 1HYJ; NMR; -; A=1347-1411.
DR PDB; 1JOC; X-ray; 2.20 A; A/B=1287-1411.
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 ProteinModelPortal; Q15075; -.
DR SMR; Q15075; 36-69, 1289-1411.
DR IntAct; Q15075; 30.
DR MINT; MINT-5004646; -.
DR STRING; 9606.ENSP00000317955; -.
DR PhosphoSite; Q15075; -.
DR DMDM; 229462866; -.
DR PaxDb; Q15075; -.
DR PRIDE; Q15075; -.
DR DNASU; 8411; -.
DR Ensembl; ENST00000322349; ENSP00000317955; ENSG00000102189.
DR GeneID; 8411; -.
DR KEGG; hsa:8411; -.
DR UCSC; uc001tck.3; human.
DR CTD; 8411; -.
DR GeneCards; GC12M093102; -.
DR HGNC; HGNC:3185; EEA1.
DR HPA; CAB005861; -.
DR HPA; CAB018782; -.
DR HPA; HPA038158; -.
DR HPA; HPA038159; -.
DR MIM; 605070; gene.
DR neXtProt; NX_Q15075; -.
DR PharmGKB; PA27621; -.
DR eggNOG; NOG12793; -.
DR HOGENOM; HOG000112329; -.
DR HOVERGEN; HBG039440; -.
DR InParanoid; Q15075; -.
DR KO; K12478; -.
DR OMA; NANSEAT; -.
DR OrthoDB; EOG754HNM; -.
DR ChiTaRS; EEA1; human.
DR EvolutionaryTrace; Q15075; -.
DR GeneWiki; EEA1; -.
DR GenomeRNAi; 8411; -.
DR NextBio; 31490; -.
DR PMAP-CutDB; Q15075; -.
DR PRO; PR:Q15075; -.
DR ArrayExpress; Q15075; -.
DR Bgee; Q15075; -.
DR CleanEx; HS_EEA1; -.
DR Genevestigator; Q15075; -.
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:0019897; C:extrinsic to plasma membrane; IDA:UniProtKB.
DR GO; GO:0055037; C:recycling endosome; IEA:Ensembl.
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: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; IPR007087; Znf_C2H2.
DR InterPro; IPR015880; Znf_C2H2-like.
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 SMART; SM00355; ZnF_C2H2; 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; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Endosome; Membrane; Metal-binding;
KW Phosphoprotein; Polymorphism; Reference proteome; Zinc; Zinc-finger.
FT CHAIN 1 1411 Early endosome antigen 1.
FT /FTId=PRO_0000098706.
FT ZN_FING 41 64 C2H2-type.
FT ZN_FING 1352 1410 FYVE-type.
FT COILED 74 1348 Potential.
FT COMPBIAS 397 758 Gln/Glu/Lys-rich.
FT COMPBIAS 937 1032 Gln/Glu/Lys-rich.
FT COMPBIAS 1093 1231 Glu/Lys-rich.
FT MOD_RES 70 70 Phosphoserine.
FT VARIANT 810 810 K -> Q (in dbSNP:rs10745623).
FT /FTId=VAR_052980.
FT MUTAGEN 39 39 E->A: Strongly reduces interaction with
FT RAB5C.
FT MUTAGEN 41 41 F->A: Strongly reduces interaction with
FT RAB5C.
FT MUTAGEN 42 42 I->A: Strongly reduces interaction with
FT RAB5C.
FT MUTAGEN 44 44 P->A: Strongly reduces interaction with
FT RAB5C.
FT MUTAGEN 47 47 M->A: Strongly reduces interaction with
FT RAB5C.
FT MUTAGEN 60 60 Y->A: Strongly reduces interaction with
FT RAB5C.
FT MUTAGEN 1349 1349 W->A: Reduces phosphatidylinositol 3-
FT phosphate binding and endosomal location.
FT MUTAGEN 1352 1352 D->V: Reduces phosphatidylinositol 3-
FT phosphate binding and endosomal location.
FT MUTAGEN 1357 1357 N->D: Reduces phosphatidylinositol 3-
FT phosphate binding and endosomal location.
FT MUTAGEN 1358 1358 C->S: Abolishes phosphatidylinositol 3-
FT phosphate binding and endosomal location.
FT MUTAGEN 1365 1365 F->A: Strongly reduces
FT phosphatidylinositol 3-phosphate binding
FT and endosomal location.
FT MUTAGEN 1367 1368 VT->EE,GG: Abolishes phosphatidylinositol
FT 3-phosphate binding and endosomal
FT location.
FT MUTAGEN 1370 1370 R->A: Abolishes endosomal location.
FT MUTAGEN 1371 1371 R->A: Abolishes phosphatidylinositol 3-
FT phosphate binding and endosomal location.
FT MUTAGEN 1372 1372 H->A: Abolishes endosomal location.
FT Abolishes pH sensitivity of the FYVE-type
FT zinc finger domain; when associated with
FT A-1373.
FT MUTAGEN 1373 1373 H->A: Abolishes phosphatidylinositol 3-
FT phosphate binding and endosomal location.
FT Abolishes pH sensitivity of the FYVE-type
FT zinc finger domain; when associated with
FT A-1372.
FT MUTAGEN 1374 1374 C->A: Abolishes phosphatidylinositol 3-
FT phosphate binding and endosomal location.
FT MUTAGEN 1375 1375 R->G: Abolishes phosphatidylinositol 3-
FT phosphate binding and endosomal location.
FT MUTAGEN 1377 1377 C->A: Abolishes phosphatidylinositol 3-
FT phosphate binding and endosomal location.
FT MUTAGEN 1378 1378 G->A: Abolishes phosphatidylinositol 3-
FT phosphate binding and endosomal location.
FT MUTAGEN 1385 1385 C->A: Abolishes phosphatidylinositol 3-
FT phosphate binding and endosomal location.
FT MUTAGEN 1400 1400 R->G: Strongly reduces
FT phosphatidylinositol 3-phosphate binding
FT and abolishes endosomal location.
FT MUTAGEN 1405 1405 C->S: Abolishes phosphatidylinositol 3-
FT phosphate binding and endosomal location.
FT CONFLICT 255 255 C -> S (in Ref. 1; AAA79121).
FT CONFLICT 258 259 LQ -> FE (in Ref. 1; AAA79121).
FT CONFLICT 277 277 A -> S (in Ref. 1; AAA79121).
FT CONFLICT 284 284 A -> R (in Ref. 1; AAA79121).
FT CONFLICT 520 520 D -> E (in Ref. 1; AAA79121).
FT CONFLICT 575 576 EQ -> DE (in Ref. 1; AAA79121).
FT CONFLICT 583 584 KL -> NV (in Ref. 1; AAA79121).
FT CONFLICT 680 680 Q -> H (in Ref. 1; AAA79121).
FT CONFLICT 1325 1325 Missing (in Ref. 1; AAA79121).
FT STRAND 38 42
FT TURN 44 46
FT STRAND 49 52
FT HELIX 53 63
FT STRAND 65 67
FT HELIX 1290 1324
FT HELIX 1326 1346
FT HELIX 1352 1354
FT TURN 1359 1361
FT STRAND 1367 1369
FT STRAND 1371 1373
FT TURN 1375 1377
FT STRAND 1380 1382
FT HELIX 1383 1385
FT STRAND 1388 1390
FT TURN 1393 1396
FT STRAND 1399 1401
FT HELIX 1403 1408
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
//
ID EEA1_HUMAN Reviewed; 1411 AA.
AC Q15075; Q14221;
DT 22-AUG-2003, integrated into UniProtKB/Swiss-Prot.
read moreDT 05-MAY-2009, sequence version 2.
DT 22-JAN-2014, entry version 118.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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.,
RA Parton R.G., Campbell P.L., McCluskey J., Yeo J.-P., Tock E.P.C.,
RA Toh B.-H.;
RT "EEA1, an early endosome-associated protein. EEA1 is a conserved
RT alpha-helical peripheral membrane protein flanked by cysteine
RT 'fingers' and 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.,
RA Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D.,
RA Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z.,
RA Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H.,
RA Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H.,
RA Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V.,
RA Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J.,
RA Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A.,
RA Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M.,
RA Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E.,
RA 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.,
RA Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R.,
RA Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J.,
RA Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C.,
RA Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M.,
RA Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M.,
RA Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P.,
RA Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L.,
RA Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E.,
RA Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C.,
RA Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F.,
RA Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M.,
RA Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S.,
RA 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.,
RA Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I.,
RA Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T.,
RA Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S.,
RA Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D.,
RA Kucherlapati R., Weinstock G., 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 MASS 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;
RP HIS-1372; HIS-1373; CYS-1374; ARG-1375; CYS-1377; GLY-1378; CYS-1385;
RP ARG-1400 AND CYS-1405, SUBCELLULAR LOCATION, AND INTERACTION WITH
RP PHOSPHATIDYLINOSITOL 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-
RT phosphate and early endosomes. Role of conserved residues.";
RL J. Biol. Chem. 275:24595-24600(2000).
RN [10]
RP INTERACTION WITH RAB22A.
RX PubMed=11870209;
RA Kauppi M., Simonsen A., Bremnes B., Vieira A., Callaghan J.M.,
RA Stenmark H., Olkkonen V.M.;
RT "The small GTPase Rab22 interacts with EEA1 and controls endosomal
RT membrane 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
RT endosome 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
RT cell 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
RP 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 MASS
RP SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation 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.,
RA Buerckstuemmer T., 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.,
RA Platta H.W., Liestol K., Stenmark H.;
RT "The PtdIns3P-binding protein Phafin 2 mediates epidermal growth
RT factor receptor degradation by promoting endosome fusion.";
RL Traffic 13:1547-1563(2012).
RN [18]
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.,
RA Lawe D., Corvera S., Lambright D.G.;
RT "Multivalent endosome targeting by homodimeric EEA1.";
RL Mol. Cell 8:947-958(2001).
RN [19]
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
CC phosphatidylinositol 3-phosphate and participates in endosomal
CC trafficking.
CC -!- SUBUNIT: Homodimer. Binds STX6. Binds RAB5A, RAB5B, RAB5C and
CC RAB22A that have been activated by GTP-binding. Interacts with
CC RAB31. Interacts with ERBB2. May interact with PLEKHF2.
CC -!- INTERACTION:
CC P04626:ERBB2; NbExp=5; IntAct=EBI-298113, EBI-641062;
CC Q9UL26:RAB22A; NbExp=3; IntAct=EBI-298113, EBI-399456;
CC P20339:RAB5A; NbExp=4; IntAct=EBI-298113, EBI-399437;
CC P61020:RAB5B; NbExp=3; IntAct=EBI-298113, EBI-399401;
CC Q5K651:SAMD9; NbExp=2; IntAct=EBI-298113, EBI-2814750;
CC Q69Z37:Samd9l (xeno); NbExp=2; IntAct=EBI-298113, EBI-8784283;
CC Q63635:Stx6 (xeno); NbExp=4; IntAct=EBI-298113, EBI-398854;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Early endosome membrane;
CC Peripheral membrane protein.
CC -!- DOMAIN: The FYVE-type zinc finger domain mediates interactions
CC with phosphatidylinositol 3-phosphate in membranes of early
CC endosomes and penetrates bilayers. The FYVE domain insertion into
CC PtdIns(3)P-enriched membranes is substantially increased in acidic
CC conditions.
CC -!- MISCELLANEOUS: Antibodies against EEA1 are found in sera from
CC patients with subacute cutaneous lupus erythematosus and other
CC autoimmune diseases.
CC -!- SIMILARITY: Contains 1 C2H2-type zinc finger.
CC -!- SIMILARITY: Contains 1 FYVE-type zinc finger.
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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 PIR; A57013; A57013.
DR RefSeq; NP_003557.2; NM_003566.3.
DR UniGene; Hs.567367; -.
DR PDB; 1HYI; NMR; -; A=1347-1411.
DR PDB; 1HYJ; NMR; -; A=1347-1411.
DR PDB; 1JOC; X-ray; 2.20 A; A/B=1287-1411.
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 ProteinModelPortal; Q15075; -.
DR SMR; Q15075; 36-69, 1289-1411.
DR IntAct; Q15075; 30.
DR MINT; MINT-5004646; -.
DR STRING; 9606.ENSP00000317955; -.
DR PhosphoSite; Q15075; -.
DR DMDM; 229462866; -.
DR PaxDb; Q15075; -.
DR PRIDE; Q15075; -.
DR DNASU; 8411; -.
DR Ensembl; ENST00000322349; ENSP00000317955; ENSG00000102189.
DR GeneID; 8411; -.
DR KEGG; hsa:8411; -.
DR UCSC; uc001tck.3; human.
DR CTD; 8411; -.
DR GeneCards; GC12M093102; -.
DR HGNC; HGNC:3185; EEA1.
DR HPA; CAB005861; -.
DR HPA; CAB018782; -.
DR HPA; HPA038158; -.
DR HPA; HPA038159; -.
DR MIM; 605070; gene.
DR neXtProt; NX_Q15075; -.
DR PharmGKB; PA27621; -.
DR eggNOG; NOG12793; -.
DR HOGENOM; HOG000112329; -.
DR HOVERGEN; HBG039440; -.
DR InParanoid; Q15075; -.
DR KO; K12478; -.
DR OMA; NANSEAT; -.
DR OrthoDB; EOG754HNM; -.
DR ChiTaRS; EEA1; human.
DR EvolutionaryTrace; Q15075; -.
DR GeneWiki; EEA1; -.
DR GenomeRNAi; 8411; -.
DR NextBio; 31490; -.
DR PMAP-CutDB; Q15075; -.
DR PRO; PR:Q15075; -.
DR ArrayExpress; Q15075; -.
DR Bgee; Q15075; -.
DR CleanEx; HS_EEA1; -.
DR Genevestigator; Q15075; -.
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:0019897; C:extrinsic to plasma membrane; IDA:UniProtKB.
DR GO; GO:0055037; C:recycling endosome; IEA:Ensembl.
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: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; IPR007087; Znf_C2H2.
DR InterPro; IPR015880; Znf_C2H2-like.
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 SMART; SM00355; ZnF_C2H2; 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; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Endosome; Membrane; Metal-binding;
KW Phosphoprotein; Polymorphism; Reference proteome; Zinc; Zinc-finger.
FT CHAIN 1 1411 Early endosome antigen 1.
FT /FTId=PRO_0000098706.
FT ZN_FING 41 64 C2H2-type.
FT ZN_FING 1352 1410 FYVE-type.
FT COILED 74 1348 Potential.
FT COMPBIAS 397 758 Gln/Glu/Lys-rich.
FT COMPBIAS 937 1032 Gln/Glu/Lys-rich.
FT COMPBIAS 1093 1231 Glu/Lys-rich.
FT MOD_RES 70 70 Phosphoserine.
FT VARIANT 810 810 K -> Q (in dbSNP:rs10745623).
FT /FTId=VAR_052980.
FT MUTAGEN 39 39 E->A: Strongly reduces interaction with
FT RAB5C.
FT MUTAGEN 41 41 F->A: Strongly reduces interaction with
FT RAB5C.
FT MUTAGEN 42 42 I->A: Strongly reduces interaction with
FT RAB5C.
FT MUTAGEN 44 44 P->A: Strongly reduces interaction with
FT RAB5C.
FT MUTAGEN 47 47 M->A: Strongly reduces interaction with
FT RAB5C.
FT MUTAGEN 60 60 Y->A: Strongly reduces interaction with
FT RAB5C.
FT MUTAGEN 1349 1349 W->A: Reduces phosphatidylinositol 3-
FT phosphate binding and endosomal location.
FT MUTAGEN 1352 1352 D->V: Reduces phosphatidylinositol 3-
FT phosphate binding and endosomal location.
FT MUTAGEN 1357 1357 N->D: Reduces phosphatidylinositol 3-
FT phosphate binding and endosomal location.
FT MUTAGEN 1358 1358 C->S: Abolishes phosphatidylinositol 3-
FT phosphate binding and endosomal location.
FT MUTAGEN 1365 1365 F->A: Strongly reduces
FT phosphatidylinositol 3-phosphate binding
FT and endosomal location.
FT MUTAGEN 1367 1368 VT->EE,GG: Abolishes phosphatidylinositol
FT 3-phosphate binding and endosomal
FT location.
FT MUTAGEN 1370 1370 R->A: Abolishes endosomal location.
FT MUTAGEN 1371 1371 R->A: Abolishes phosphatidylinositol 3-
FT phosphate binding and endosomal location.
FT MUTAGEN 1372 1372 H->A: Abolishes endosomal location.
FT Abolishes pH sensitivity of the FYVE-type
FT zinc finger domain; when associated with
FT A-1373.
FT MUTAGEN 1373 1373 H->A: Abolishes phosphatidylinositol 3-
FT phosphate binding and endosomal location.
FT Abolishes pH sensitivity of the FYVE-type
FT zinc finger domain; when associated with
FT A-1372.
FT MUTAGEN 1374 1374 C->A: Abolishes phosphatidylinositol 3-
FT phosphate binding and endosomal location.
FT MUTAGEN 1375 1375 R->G: Abolishes phosphatidylinositol 3-
FT phosphate binding and endosomal location.
FT MUTAGEN 1377 1377 C->A: Abolishes phosphatidylinositol 3-
FT phosphate binding and endosomal location.
FT MUTAGEN 1378 1378 G->A: Abolishes phosphatidylinositol 3-
FT phosphate binding and endosomal location.
FT MUTAGEN 1385 1385 C->A: Abolishes phosphatidylinositol 3-
FT phosphate binding and endosomal location.
FT MUTAGEN 1400 1400 R->G: Strongly reduces
FT phosphatidylinositol 3-phosphate binding
FT and abolishes endosomal location.
FT MUTAGEN 1405 1405 C->S: Abolishes phosphatidylinositol 3-
FT phosphate binding and endosomal location.
FT CONFLICT 255 255 C -> S (in Ref. 1; AAA79121).
FT CONFLICT 258 259 LQ -> FE (in Ref. 1; AAA79121).
FT CONFLICT 277 277 A -> S (in Ref. 1; AAA79121).
FT CONFLICT 284 284 A -> R (in Ref. 1; AAA79121).
FT CONFLICT 520 520 D -> E (in Ref. 1; AAA79121).
FT CONFLICT 575 576 EQ -> DE (in Ref. 1; AAA79121).
FT CONFLICT 583 584 KL -> NV (in Ref. 1; AAA79121).
FT CONFLICT 680 680 Q -> H (in Ref. 1; AAA79121).
FT CONFLICT 1325 1325 Missing (in Ref. 1; AAA79121).
FT STRAND 38 42
FT TURN 44 46
FT STRAND 49 52
FT HELIX 53 63
FT STRAND 65 67
FT HELIX 1290 1324
FT HELIX 1326 1346
FT HELIX 1352 1354
FT TURN 1359 1361
FT STRAND 1367 1369
FT STRAND 1371 1373
FT TURN 1375 1377
FT STRAND 1380 1382
FT HELIX 1383 1385
FT STRAND 1388 1390
FT TURN 1393 1396
FT STRAND 1399 1401
FT HELIX 1403 1408
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
//
MIM
605070
*RECORD*
*FIELD* NO
605070
*FIELD* TI
*605070 EARLY ENDOSOME ANTIGEN 1; EEA1
;;EARLY ENDOSOME ANTIGEN, 162-KD
*FIELD* TX
read moreEarly endosomes are cellular compartments that receive endocytosed
materials and sort them for vesicular transport to late endosomes and
lysosomes or for recycling to the plasma membrane.
CLONING
By screening a HeLa cell expression library with autoimmune serum, Mu et
al. (1995) obtained a cDNA encoding EEA1. Sequence analysis predicted
that the 1,411-amino acid EEA1 protein is largely hydrophilic with short
amphiphilic regions in the 15 N-terminal amino acids and in segments
centered around amino acids 515 and 645. EEA1 contains an N-terminal
zinc finger motif, a cys-rich C-terminal metal-binding finger, and
multiple sites for N-glycosylation, phosphorylation, N-myristoylation,
and for a leucine zipper structure. Northern blot analysis detected a
9.0-kb EEA1 transcript in skeletal muscle, heart, brain, lung, liver,
and pancreas. Immunoblot analysis determined that EEA1 is expressed as a
180-kD protein in membrane and cytosolic fractions. Immunofluorescence
microscopy showed that EEA1 colocalizes with transferrin (TF; 190000)
and with RAB5 (RAB5A; 179512), which localizes in early endosomes, but
not with RAB7 (602298), which localizes in late endosomes.
BIOCHEMICAL FEATURES
Using yeast 2-hybrid analysis, Simonsen et al. (1998) found that the
N-terminal zinc finger and the C-terminal FYVE finger of EEA1 bind to
RAB5 or RAB5-GTP and to phosphatidylinositol 3-phosphate (PtdIns(3)P),
respectively. Each of these interactions stabilizes the binding of EEA1
to the endosomal membrane.
Kutateladze and Overduin (2001) determined the solution structure of the
FYVE domain of EEA1 protein in the free state and compared it with the
structures of the domain complexed with phosphatidylinositol 3-phosphate
and mixed micelles. The multistep binding mechanism involved nonspecific
insertion of a hydrophobic loop into the lipid bilayer, positioning and
activating the binding pocket. Ligation of phosphatidylinositol
3-phosphate then induced a global structural change, drawing the protein
termini over the bound phosphoinositide by extension of a hinge.
Specific recognition of the 3-phosphate was determined indirectly and
directly by 2 clusters of conserved arginines.
To determine the structural basis for selective PtdIns(3)P recognition
by FYVE domains and the role of domain organization, dimerization, and
quaternary structure with respect to EEA1 localization and endosome
tethering, Dumas et al. (2001) characterized the binding of soluble
phosphoinositides to monomeric and homodimeric constructs of EEA1 and
determined the crystal structure of the homodimeric C-terminal region as
a complex with the head group of PtdIns(3)P. A specific head group
binding mode showed how FYVE domains selectively recognize PtdIns(3)P
and discriminate against other mono- or polyphosphorylated species. The
EEA1 homodimer was found to be ideally configured for multivalent
membrane engagement. The simplest thermodynamic model for bivalent
recognition of PtdIns(3)P in a lipid bilayer quantitatively accounted
for the large amplification of the weak affinity and moderate
specificity of soluble PtdIns(3)P binding to the EEA1 FYVE domain and
explained why the region preceding the FYVE domain is required for
localization to early endosomes.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the EEA1
gene to chromosome 12 (TMAP sts-X78998).
*FIELD* RF
1. Dumas, J. J.; Merithew, E.; Sudharshan, E.; Rajamani, D.; Hayes,
S.; Lawe, D.; Corvera, S.; Lambright, D. G.: Multivalent endosome
targeting by homodimeric EEA1. Molec. Cell 8: 947-958, 2001.
2. Kutateladze, T.; Overduin, M.: Structural mechanism of endosome
docking by the FYVE domain. Science 291: 1793-1796, 2001.
3. Mu, F.-T.; Callaghan, J. M.; Steele-Mortimer, O.; Stenmark, H.;
Parton, R. G.; Campbell, P. L.; McCluskey, J.; Yeo, J.-P.; Tock, E.
P. C.; Toh, B.-H.: EEA1, an early endosome-associated protein: EEA1
is a conserved alpha-helical peripheral membrane protein flanked by
cysteine 'fingers' and contains a calmodulin-binding IQ motif. J.
Biol. Chem. 270: 13503-13511, 1995.
4. Simonsen, A.; Lippe, R.; Christoforidis, S.; Gaullier, J.-M.; Brech,
A.; Callaghan, J.; Toh, B.-H.; Murphy, C.; Zerial, M.; Stenmark, H.
: EEA1 links PI(3)K function to Rab5 regulation of endosome fusion. Nature 394:
494-498, 1998.
*FIELD* CN
Ada Hamosh - updated: 3/5/2002
Stylianos E. Antonarakis - updated: 1/2/2002
*FIELD* CD
Paul J. Converse: 6/23/2000
*FIELD* ED
alopez: 03/07/2002
terry: 3/5/2002
mgross: 1/2/2002
mgross: 6/28/2000
mgross: 6/23/2000
*RECORD*
*FIELD* NO
605070
*FIELD* TI
*605070 EARLY ENDOSOME ANTIGEN 1; EEA1
;;EARLY ENDOSOME ANTIGEN, 162-KD
*FIELD* TX
read moreEarly endosomes are cellular compartments that receive endocytosed
materials and sort them for vesicular transport to late endosomes and
lysosomes or for recycling to the plasma membrane.
CLONING
By screening a HeLa cell expression library with autoimmune serum, Mu et
al. (1995) obtained a cDNA encoding EEA1. Sequence analysis predicted
that the 1,411-amino acid EEA1 protein is largely hydrophilic with short
amphiphilic regions in the 15 N-terminal amino acids and in segments
centered around amino acids 515 and 645. EEA1 contains an N-terminal
zinc finger motif, a cys-rich C-terminal metal-binding finger, and
multiple sites for N-glycosylation, phosphorylation, N-myristoylation,
and for a leucine zipper structure. Northern blot analysis detected a
9.0-kb EEA1 transcript in skeletal muscle, heart, brain, lung, liver,
and pancreas. Immunoblot analysis determined that EEA1 is expressed as a
180-kD protein in membrane and cytosolic fractions. Immunofluorescence
microscopy showed that EEA1 colocalizes with transferrin (TF; 190000)
and with RAB5 (RAB5A; 179512), which localizes in early endosomes, but
not with RAB7 (602298), which localizes in late endosomes.
BIOCHEMICAL FEATURES
Using yeast 2-hybrid analysis, Simonsen et al. (1998) found that the
N-terminal zinc finger and the C-terminal FYVE finger of EEA1 bind to
RAB5 or RAB5-GTP and to phosphatidylinositol 3-phosphate (PtdIns(3)P),
respectively. Each of these interactions stabilizes the binding of EEA1
to the endosomal membrane.
Kutateladze and Overduin (2001) determined the solution structure of the
FYVE domain of EEA1 protein in the free state and compared it with the
structures of the domain complexed with phosphatidylinositol 3-phosphate
and mixed micelles. The multistep binding mechanism involved nonspecific
insertion of a hydrophobic loop into the lipid bilayer, positioning and
activating the binding pocket. Ligation of phosphatidylinositol
3-phosphate then induced a global structural change, drawing the protein
termini over the bound phosphoinositide by extension of a hinge.
Specific recognition of the 3-phosphate was determined indirectly and
directly by 2 clusters of conserved arginines.
To determine the structural basis for selective PtdIns(3)P recognition
by FYVE domains and the role of domain organization, dimerization, and
quaternary structure with respect to EEA1 localization and endosome
tethering, Dumas et al. (2001) characterized the binding of soluble
phosphoinositides to monomeric and homodimeric constructs of EEA1 and
determined the crystal structure of the homodimeric C-terminal region as
a complex with the head group of PtdIns(3)P. A specific head group
binding mode showed how FYVE domains selectively recognize PtdIns(3)P
and discriminate against other mono- or polyphosphorylated species. The
EEA1 homodimer was found to be ideally configured for multivalent
membrane engagement. The simplest thermodynamic model for bivalent
recognition of PtdIns(3)P in a lipid bilayer quantitatively accounted
for the large amplification of the weak affinity and moderate
specificity of soluble PtdIns(3)P binding to the EEA1 FYVE domain and
explained why the region preceding the FYVE domain is required for
localization to early endosomes.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the EEA1
gene to chromosome 12 (TMAP sts-X78998).
*FIELD* RF
1. Dumas, J. J.; Merithew, E.; Sudharshan, E.; Rajamani, D.; Hayes,
S.; Lawe, D.; Corvera, S.; Lambright, D. G.: Multivalent endosome
targeting by homodimeric EEA1. Molec. Cell 8: 947-958, 2001.
2. Kutateladze, T.; Overduin, M.: Structural mechanism of endosome
docking by the FYVE domain. Science 291: 1793-1796, 2001.
3. Mu, F.-T.; Callaghan, J. M.; Steele-Mortimer, O.; Stenmark, H.;
Parton, R. G.; Campbell, P. L.; McCluskey, J.; Yeo, J.-P.; Tock, E.
P. C.; Toh, B.-H.: EEA1, an early endosome-associated protein: EEA1
is a conserved alpha-helical peripheral membrane protein flanked by
cysteine 'fingers' and contains a calmodulin-binding IQ motif. J.
Biol. Chem. 270: 13503-13511, 1995.
4. Simonsen, A.; Lippe, R.; Christoforidis, S.; Gaullier, J.-M.; Brech,
A.; Callaghan, J.; Toh, B.-H.; Murphy, C.; Zerial, M.; Stenmark, H.
: EEA1 links PI(3)K function to Rab5 regulation of endosome fusion. Nature 394:
494-498, 1998.
*FIELD* CN
Ada Hamosh - updated: 3/5/2002
Stylianos E. Antonarakis - updated: 1/2/2002
*FIELD* CD
Paul J. Converse: 6/23/2000
*FIELD* ED
alopez: 03/07/2002
terry: 3/5/2002
mgross: 1/2/2002
mgross: 6/28/2000
mgross: 6/23/2000