ID   E9PFD7_HUMAN            Unreviewed;      1165 AA.
AC   E9PFD7;
DT   05-APR-2011, integrated into UniProtKB/TrEMBL.
DT   29-OCT-2014, sequence version 3.
DT   16-JAN-2019, entry version 75.
DE   RecName: Full=Receptor protein-tyrosine kinase {ECO:0000256|SAAS:SAAS00593197};
DE            EC=2.7.10.1 {ECO:0000256|SAAS:SAAS00593197};
GN   Name=EGFR {ECO:0000313|Ensembl:ENSP00000395243};
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 {ECO:0000313|Ensembl:ENSP00000395243, ECO:0000313|Proteomes:UP000005640};
RN   [1] {ECO:0000313|Ensembl:ENSP00000395243, ECO:0000313|Proteomes:UP000005640}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=12853948; DOI=10.1038/nature01782;
RA   Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA   Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R.,
RA   Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E.,
RA   Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H.,
RA   Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A.,
RA   Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J.,
RA   Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A.,
RA   Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S.,
RA   Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M.,
RA   Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C.,
RA   Latreille P., Miller N., Johnson D., Murray J., Woessner J.P.,
RA   Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J.,
RA   Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L.,
RA   Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R.,
RA   Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA   Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K.,
RA   Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S.,
RA   Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M.,
RA   Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R.,
RA   Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D.,
RA   Waterston R.H., Wilson R.K.;
RT   "The DNA sequence of human chromosome 7.";
RL   Nature 424:157-164(2003).
RN   [2] {ECO:0000213|PubMed:17081983}
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA   Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA   Mann M.;
RT   "Global, in vivo, and site-specific phosphorylation dynamics in
RT   signaling networks.";
RL   Cell 127:635-648(2006).
RN   [3] {ECO:0000213|PubMed:18220336}
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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.;
RT   "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for
RT   efficient phosphoproteomic analysis.";
RL   J. Proteome Res. 7:1346-1351(2008).
RN   [4] {ECO:0000213|PubMed:18691976}
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA   Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA   Greff Z., Keri G., Stemmann O., Mann M.;
RT   "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT   the kinome across the cell cycle.";
RL   Mol. Cell 31:438-448(2008).
RN   [5] {ECO:0000213|PubMed:18669648}
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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   [6] {ECO:0000213|PubMed:19413330}
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.,
RA   Mohammed S.;
RT   "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT   a refined SCX-based approach.";
RL   Anal. Chem. 81:4493-4501(2009).
RN   [7] {ECO:0000213|PubMed:19369195}
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
RA   Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA   Mann M., Daub H.;
RT   "Large-scale proteomics analysis of the human kinome.";
RL   Mol. Cell. Proteomics 8:1751-1764(2009).
RN   [8] {ECO:0000213|PubMed:20068231}
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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   [9] {ECO:0000213|PubMed:21269460}
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   Burckstummer 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   [10] {ECO:0000313|Ensembl:ENSP00000395243}
RP   IDENTIFICATION.
RG   Ensembl;
RL   Submitted (JUL-2011) to UniProtKB.
RN   [11] {ECO:0000213|PubMed:23186163}
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=23186163;
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   [12] {ECO:0000213|PubMed:24275569}
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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.,
RA   Wang L., Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human
RT   liver phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-
CC         tyrosyl-[protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136,
CC         Rhea:RHEA-COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:46858, ChEBI:CHEBI:82620, ChEBI:CHEBI:456216;
CC         EC=2.7.10.1; Evidence={ECO:0000256|SAAS:SAAS01123262};
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC       kinase family. {ECO:0000256|SAAS:SAAS00941529}.
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DR   EMBL; AC006977; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC073324; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; KF458469; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   RefSeq; NP_001333828.1; NM_001346899.1.
DR   UniGene; Hs.488293; -.
DR   UniGene; Hs.605083; -.
DR   UniGene; Hs.731652; -.
DR   ProteinModelPortal; E9PFD7; -.
DR   jPOST; E9PFD7; -.
DR   PeptideAtlas; E9PFD7; -.
DR   PRIDE; E9PFD7; -.
DR   Ensembl; ENST00000454757; ENSP00000395243; ENSG00000146648.
DR   GeneID; 1956; -.
DR   UCSC; uc022adn.2; human.
DR   CTD; 1956; -.
DR   EuPathDB; HostDB:ENSG00000146648.15; -.
DR   HGNC; HGNC:3236; EGFR.
DR   OpenTargets; ENSG00000146648; -.
DR   eggNOG; KOG1025; Eukaryota.
DR   eggNOG; ENOG410XNSR; LUCA.
DR   GeneTree; ENSGT00940000155450; -.
DR   OrthoDB; 81952at2759; -.
DR   ChiTaRS; EGFR; human.
DR   GenomeRNAi; 1956; -.
DR   Proteomes; UP000005640; Chromosome 7.
DR   Bgee; ENSG00000146648; Expressed in 234 organ(s), highest expression level in placenta.
DR   ExpressionAtlas; E9PFD7; baseline and differential.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IEA:UniProtKB-EC.
DR   GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IEA:InterPro.
DR   CDD; cd00064; FU; 3.
DR   Gene3D; 3.80.20.20; -; 3.
DR   InterPro; IPR006211; Furin-like_Cys-rich_dom.
DR   InterPro; IPR006212; Furin_repeat.
DR   InterPro; IPR032778; GF_recep_IV.
DR   InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   InterPro; IPR000719; Prot_kinase_dom.
DR   InterPro; IPR017441; Protein_kinase_ATP_BS.
DR   InterPro; IPR000494; Rcpt_L-dom.
DR   InterPro; IPR036941; Rcpt_L-dom_sf.
DR   InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR   InterPro; IPR008266; Tyr_kinase_AS.
DR   InterPro; IPR020635; Tyr_kinase_cat_dom.
DR   InterPro; IPR016245; Tyr_kinase_EGF/ERB/XmrK_rcpt.
DR   Pfam; PF00757; Furin-like; 1.
DR   Pfam; PF14843; GF_recep_IV; 1.
DR   Pfam; PF07714; Pkinase_Tyr; 1.
DR   Pfam; PF01030; Recep_L_domain; 2.
DR   PIRSF; PIRSF000619; TyrPK_EGF-R; 3.
DR   PRINTS; PR00109; TYRKINASE.
DR   SMART; SM00261; FU; 3.
DR   SMART; SM00219; TyrKc; 1.
DR   SUPFAM; SSF56112; SSF56112; 1.
DR   SUPFAM; SSF57184; SSF57184; 2.
DR   PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
PE   1: Evidence at protein level;
KW   ATP-binding {ECO:0000256|PIRSR:PIRSR000619-2,
KW   ECO:0000256|SAAS:SAAS00461464};
KW   Complete proteome {ECO:0000313|Proteomes:UP000005640};
KW   Kinase {ECO:0000256|SAAS:SAAS00594505};
KW   Membrane {ECO:0000256|SAM:Phobius};
KW   Nucleotide-binding {ECO:0000256|PIRSR:PIRSR000619-2,
KW   ECO:0000256|SAAS:SAAS00461464};
KW   Proteomics identification {ECO:0000213|EPD:E9PFD7,
KW   ECO:0000213|MaxQB:E9PFD7, ECO:0000213|PeptideAtlas:E9PFD7};
KW   Reference proteome {ECO:0000313|Proteomes:UP000005640};
KW   Signal {ECO:0000256|SAM:SignalP};
KW   Transferase {ECO:0000256|SAAS:SAAS00594505};
KW   Transmembrane {ECO:0000256|SAM:Phobius};
KW   Transmembrane helix {ECO:0000256|SAM:Phobius};
KW   Tyrosine-protein kinase {ECO:0000256|SAAS:SAAS00594505}.
FT   SIGNAL        1     24       {ECO:0000256|SAM:SignalP}.
FT   CHAIN        25   1165       Receptor protein-tyrosine kinase.
FT                                {ECO:0000256|SAM:SignalP}.
FT                                /FTId=PRO_5003244049.
FT   TRANSMEM    601    622       Helical. {ECO:0000256|SAM:Phobius}.
FT   DOMAIN      667    934       Protein kinase.
FT                                {ECO:0000259|PROSITE:PS50011}.
FT   NP_BIND     673    681       ATP. {ECO:0000256|PIRSR:PIRSR000619-2}.
FT   ACT_SITE    792    792       Proton acceptor.
FT                                {ECO:0000256|PIRSR:PIRSR000619-1}.
FT   BINDING     700    700       ATP. {ECO:0000256|PIRSR:PIRSR000619-2}.
SQ   SEQUENCE   1165 AA;  129169 MW;  9CEE26B795A041B2 CRC64;
     MRPSGTAGAA LLALLAALCP ASRALEEKKV CQGTSNKLTQ LGTFEDHFLS LQRMFNNCEV
     VLGNLEITYV QRNYDLSFLK TIQEVAGYVL IALNTVERIP LENLQIIRGN MYYENSYALA
     VLSNYDANKT GLKELPMRNL QGQKCDPSCP NGSCWGAGEE NCQKLTKIIC AQQCSGRCRG
     KSPSDCCHNQ CAAGCTGPRE SDCLVCRKFR DEATCKDTCP PLMLYNPTTY QMDVNPEGKY
     SFGATCVKKC PRNYVVTDHG SCVRACGADS YEMEEDGVRK CKKCEGPCRK VCNGIGIGEF
     KDSLSINATN IKHFKNCTSI SGDLHILPVA FRGDSFTHTP PLDPQELDIL KTVKEITGFL
     LIQAWPENRT DLHAFENLEI IRGRTKQHGQ FSLAVVSLNI TSLGLRSLKE ISDGDVIISG
     NKNLCYANTI NWKKLFGTSG QKTKIISNRG ENSCKATGQV CHALCSPEGC WGPEPRDCVS
     CRNVSRGREC VDKCNLLEGE PREFVENSEC IQCHPECLPQ AMNITCTGRG PDNCIQCAHY
     IDGPHCVKTC PAGVMGENNT LVWKYADAGH VCHLCHPNCT YGCTGPGLEG CPTNGPKIPS
     IATGMVGALL LLLVVALGIG LFMRRRHIVR KRTLRRLLQE RELVEPLTPS GEAPNQALLR
     ILKETEFKKI KVLGSGAFGT VYKGLWIPEG EKVKIPVAIK ELREATSPKA NKEILDEAYV
     MASVDNPHVC RLLGICLTST VQLITQLMPF GCLLDYVREH KDNIGSQYLL NWCVQIAKGM
     NYLEDRRLVH RDLAARNVLV KTPQHVKITD FGLAKLLGAE EKEYHAEGGK VPIKWMALES
     ILHRIYTHQS DVWSYGVTVW ELMTFGSKPY DGIPASEISS ILEKGERLPQ PPICTIDVYM
     IMVKCWMIDA DSRPKFRELI IEFSKMARDP QRYLVIQGDE RMHLPSPTDS NFYRALMDEE
     DMDDVVDADE YLIPQQGFFS SPSTSRTPLL SSLSATSNNS TVACIDRNGL QSCPIKEDSF
     LQRYSSDPTG ALTEDSIDDT FLPVPEYINQ SVPKRPAGSV QNPVYHNQPL NPAPSRDPHY
     QDPHSTAVGN PEYLNTVQPT CVNSTFDSPA HWAQKGSHQI SLDNPDYQQD FFPKEAKPNG
     IFKGSTAENA EYLRVAPQSS EFIGA
//