ID EGFR_HUMAN STANDARD; PRT; 1210 AA. AC P00533; O00688; O00732; P06268; Q14225; Q92795; Q9BZS2; Q9GZX1; AC Q9H2C9; Q9H3C9; Q9UMD7; Q9UMD8; Q9UMG5; DT 21-JUL-1986 (Rel. 01, Created) DT 01-NOV-1997 (Rel. 35, Last sequence update) DT 15-SEP-2003 (Rel. 42, Last annotation update) DE Epidermal growth factor receptor precursor (EC 2.7.1.112) (Receptor DE protein-tyrosine kinase ErbB-1). GN EGFR OR ERBB1. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. (ISOFORM 1). RX MEDLINE=84219729; PubMed=6328312; RA Ullrich A., Coussens L., Hayflick J.S., Dull T.J., Gray A., Tam A.W., RA Lee J., Yarden Y., Libermann T.A., Schlessinger J., Downward J., RA Mayes E.L.V., Whittle N., Waterfield M.D., Seeburg P.H.; RT "Human epidermal growth factor receptor cDNA sequence and aberrant RT expression of the amplified gene in A431 epidermoid carcinoma cells."; RL Nature 309:418-425(1984). RN [2] RP SEQUENCE FROM N.A. (ISOFORM 2). RC TISSUE=Placenta; RX MEDLINE=95382957; PubMed=7654368; RA Ilekis J.V., Stark B.C., Scoccia B.; RT "Possible role of variant RNA transcripts in the regulation of RT epidermal growth factor receptor expression in human placenta."; RL Mol. Reprod. Dev. 41:149-156(1995). RN [3] RP SEQUENCE FROM N.A. (ISOFORM 2). RC TISSUE=Placenta; RX MEDLINE=97078686; PubMed=8918811; RA Reiter J.L., Maihle N.J.; RT "A 1.8 kb alternative transcript from the human epidermal growth RT factor receptor gene encodes a truncated form of the receptor."; RL Nucleic Acids Res. 24:4050-4056(1996). RN [4] RP SEQUENCE FROM N.A. (ISOFORM 2). RC TISSUE=Placenta; RX MEDLINE=97256547; PubMed=9103388; RA Ilekis J.V., Gariti J., Niederberger C., Scoccia B.; RT "Expression of a truncated epidermal growth factor receptor-like RT protein (TEGFR) in ovarian cancer."; RL Gynecol. Oncol. 65:36-41(1997). RN [5] RP SEQUENCE FROM N.A. (ISOFORMS 3 AND 4). RC TISSUE=Placenta; RX MEDLINE=21100872; PubMed=11161793; RA Reiter J.L., Threadgill D.W., Eley G.D., Strunk K.E., Danielsen A.J., RA Schehl Sinclair C., Pearsall R.S., Green P.J., Yee D., Lampland A.L., RA Balasubramaniam S., Crossley T.D., Magnuson T.R., James C.D., RA Maihle N.J.; RT "Comparative genomic sequence analysis and isolation of human and RT mouse alternative EGFR transcripts encoding truncated receptor RT isoforms."; RL Genomics 71:1-20(2001). RN [6] RP SEQUENCE OF 575-687 FROM N.A. RA Reiter J.L., Threadgill D.W., Danielsen A.J., Schehl C.M., RA Lampland A.L., Balasubramaniam S., Crossley T.O., Magnuson T.R., RA Maihle N.J.; RT "Human and mouse alternative EGFR transcripts encoding only the RT extracellular domain of the receptor."; RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases. RN [7] RP SEQUENCE OF 713-924 FROM N.A. RX MEDLINE=84196372; PubMed=6326261; RA Lin C.R., Chen W.S., Kruiger W., Stolarsky L.S., Weber W., RA Evans R.M., Verma I.M., Gill G.N., Rosenfeld M.G.; RT "Expression cloning of human EGF receptor complementary DNA: gene RT amplification and three related messenger RNA products in A431 RT cells."; RL Science 224:843-848(1984). RN [8] RP SEQUENCE OF 150-962 FROM N.A. RX MEDLINE=84245835; PubMed=6330563; RA Xu Y.H., Ishii S., Clark A.J.L., Sullivan M., Wilson R.K., Ma D.P., RA Roe B.A., Merlino G.T., Pastan I.; RT "Human epidermal growth factor receptor cDNA is homologous to a RT variety of RNAs overproduced in A431 carcinoma cells."; RL Nature 309:806-810(1984). RN [9] RP SEQUENCE OF 1028-1210 FROM N.A. RX MEDLINE=85046483; PubMed=6093780; RA Simmen F.A., Gope M.L., Schulz T.Z., Wright D.A., Carpenter G., RA O'Malley B.W.; RT "Isolation of an evolutionarily conserved epidermal growth factor RT receptor cDNA from human A431 carcinoma cells."; RL Biochem. Biophys. Res. Commun. 124:125-132(1984). RN [10] RP SEQUENCE OF 1-29 FROM N.A. RX MEDLINE=88217333; PubMed=3329716; RA Haley J.D., Whittle N., Bennett P., Kinchington D., Ullrich A., RA Waterfield M.D.; RT "The human EGF receptor gene: structure of the 110 kb locus and RT identification of sequences regulating its transcription."; RL Oncogene Res. 1:375-396(1987). RN [11] RP SEQUENCE OF 1-29 FROM N.A. RX MEDLINE=91107677; PubMed=1988448; RA Haley J.D., Waterfield M.D.; RT "Contributory effects of de novo transcription and premature RT transcript termination in the regulation of human epidermal growth RT factor receptor proto-oncogene RNA synthesis."; RL J. Biol. Chem. 266:1746-1753(1991). RN [12] RP SEQUENCE OF 1-29 FROM N.A. RX MEDLINE=85270438; PubMed=2991899; RA Ishii S., Xu Y.H., Stratton R.H., Roe B.A., Merlino G.T., Pastan I.; RT "Characterization and sequence of the promoter region of the human RT epidermal growth factor receptor gene."; RL Proc. Natl. Acad. Sci. U.S.A. 82:4920-4924(1985). RN [13] RP SEQUENCE OF 540. RA Kohda D.; RL Submitted (SEP-1997) to the SWISS-PROT data bank. RN [14] RP RECEPTOR ACTIVITY. RX MEDLINE=84191554; PubMed=6325948; RA Mroczkowski B., Mosig G., Cohen S.; RT "ATP-stimulated interaction between epidermal growth factor receptor RT and supercoiled DNA."; RL Nature 309:270-273(1984). RN [15] RP PHOSPHORYLATION. RX MEDLINE=89278137; PubMed=2543678; RA Margolis B.L., Lax I., Kris R., Dombalagian M., Honegger A.M., RA Howk R., Givol D., Ullrich A., Schlessinger J.; RT "All autophosphorylation sites of epidermal growth factor (EGF) RT receptor and HER2/neu are located in their carboxyl-terminal tails. RT Identification of a novel site in EGF receptor."; RL J. Biol. Chem. 264:10667-10671(1989). RN [16] RP CARBOHYDRATE-LINKAGE SITES ASN-128; ASN-175; ASN-413; ASN-444 AND RP ASN-528. RX MEDLINE=96398132; PubMed=8962717; RA Smith K.D., Davies M.J., Bailey D., Renouf D.V., Hounsell E.F.; RT "Analysis of the glycosylation patterns of the extracellular domain of RT the epidermal growth factor receptor expressed in Chinese hamster RT ovary fibroblasts."; RL Growth Factors 13:121-132(1996). RN [17] RP CARBOHYDRATE-LINKAGE SITES ASN-56; ASN-352; ASN-361; ASN-568 AND RP ASN-603. RX MEDLINE=20198209; PubMed=10731668; RA Sato C., Kim J.-H., Abe Y., Saito K., Yokoyama S., Kohda D.; RT "Characterization of the N-oligosaccharides attached to the atypical RT Asn-X-Cys sequence of recombinant human epidermal growth factor RT receptor."; RL J. Biochem. 127:65-72(2000). RN [18] RP PARTIAL SEQUENCE, AND DISULFIDE BONDS. RX MEDLINE=98225196; PubMed=9556602; RA Abe Y., Odaka M., Inagaki F., Lax I., Schlessinger J., Kohda D.; RT "Disulfide bond structure of human epidermal growth factor receptor."; RL J. Biol. Chem. 273:11150-11157(1998). RN [19] RP REVIEW. RX MEDLINE=87297456; PubMed=3039909; RA Carpenter G.; RT "Receptors for epidermal growth factor and other polypeptide RT mitogens."; RL Annu. Rev. Biochem. 56:881-914(1987). CC -!- FUNCTION: Receptor for EGF, but also for other members of the EGF CC family, as TGF-alpha, amphiregulin, betacellulin, heparin-binding CC EGF-like growth factor, GP30 and vaccinia virus growth factor. Is CC involved in the control of cell growth and differentiation. CC -!- FUNCTION: Isoform 2/truncated isoform may act as an antagonist. CC -!- CATALYTIC ACTIVITY: ATP + a protein tyrosine = ADP + protein CC tyrosine phosphate. CC -!- SUBCELLULAR LOCATION: Type I membrane protein. Isoform 2 is CC secreted. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; Synonyms=p170; CC IsoId=P00533-1; Sequence=Displayed; CC Name=2; Synonyms=p60, Truncated, TEGFR; CC IsoId=P00533-2; Sequence=VSP_002887, VSP_002888; CC Name=3; Synonyms=p110; CC IsoId=P00533-3; Sequence=VSP_002889, VSP_002890; CC Name=4; CC IsoId=P00533-4; Sequence=VSP_002891, VSP_002892; CC -!- TISSUE SPECIFICITY: Expressed in placenta. Isoform 2 is also CC expressed in ovarian cancers. CC -!- MISCELLANEOUS: Binding of EGF to the receptor leads to CC dimerization, internalization of the EGF-receptor complex, CC induction of the tyrosine kinase activity, stimulation of cell DNA CC synthesis, and cell proliferation. CC -!- SIMILARITY: BELONGS TO THE EGF RECEPTOR FAMILY. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X00588; CAA25240.1; -. DR EMBL; U95089; AAB53063.1; -. DR EMBL; U48722; AAC50802.1; -. DR EMBL; U48723; AAC50804.1; -. DR EMBL; U48724; AAC50796.1; -. DR EMBL; U48725; AAC50797.1; -. DR EMBL; U48726; AAC50798.1; -. DR EMBL; U48727; AAC50799.1; -. DR EMBL; U48728; AAC50800.1; -. DR EMBL; U48729; AAC50801.1; -. DR EMBL; AF288738; AAG35786.1; -. DR EMBL; AF288738; AAG35787.1; -. DR EMBL; AF288738; AAG35788.1; -. DR EMBL; AF288738; AAG35789.1; -. DR EMBL; AF288738; AAG35790.1; -. DR EMBL; AF277897; AAK01080.1; -. DR EMBL; AF125253; AAG43240.1; -. DR EMBL; AF125539; AAG43243.1; -. DR EMBL; AF125538; AAG43243.1; JOINED. DR EMBL; X06370; CAA29668.1; -. DR EMBL; X00663; CAA25282.1; -. DR EMBL; M38425; AAA63171.1; -. DR EMBL; M11234; AAA52370.1; -. DR PIR; A00641; GQHUE. DR PIR; A00642; GQHUE2. DR PIR; A23062; A23062. DR HSSP; P11362; 1FGK. DR SWISS-2DPAGE; P00533; HUMAN. DR Genew; HGNC:3236; EGFR. DR MIM; 131550; -. DR GlycoSuiteDB; P00533; -. DR GO; GO:0005768; C:endosome; TAS. DR GO; GO:0008283; P:cell proliferation; TAS. DR GO; GO:0007173; P:EGF receptor signaling pathway; TAS. DR InterPro; IPR000494; EGFR_L_domain. DR InterPro; IPR006211; Furin-like. DR InterPro; IPR000719; Prot_kinase. DR InterPro; IPR001245; Tyr_pkinase. DR Pfam; PF00069; pkinase; 1. DR Pfam; PF00757; Furin-like; 1. DR Pfam; PF01030; Recep_L_domain; 2. DR PRINTS; PR00109; TYRKINASE. DR ProDom; PD000001; Prot_kinase; 1. DR SMART; SM00261; FU; 3. DR SMART; SM00219; TyrKc; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. KW Transmembrane; Glycoprotein; Repeat; Receptor; Signal; Transferase; KW Tyrosine-protein kinase; ATP-binding; Phosphorylation; KW Alternative splicing. FT SIGNAL 1 24 FT CHAIN 25 1210 EPIDERMAL GROWTH FACTOR RECEPTOR. FT DOMAIN 25 645 EXTRACELLULAR (POTENTIAL). FT TRANSMEM 646 668 POTENTIAL. FT DOMAIN 669 1210 CYTOPLASMIC (POTENTIAL). FT REPEAT 75 300 APPROXIMATE. FT REPEAT 390 600 APPROXIMATE. FT DOMAIN 1025 1071 SER-RICH. FT DOMAIN 712 979 PROTEIN KINASE. FT NP_BIND 718 726 ATP (BY SIMILARITY). FT BINDING 745 745 ATP (BY SIMILARITY). FT ACT_SITE 837 837 BY SIMILARITY. FT DISULFID 190 199 FT DISULFID 194 207 FT DISULFID 215 223 FT DISULFID 219 231 FT DISULFID 232 240 FT DISULFID 236 248 FT DISULFID 251 260 FT DISULFID 264 291 FT DISULFID 295 307 FT DISULFID 311 326 FT DISULFID 329 333 FT DISULFID 506 515 FT DISULFID 510 523 FT DISULFID 526 535 FT DISULFID 539 555 FT DISULFID 558 571 FT DISULFID 562 579 FT DISULFID 582 591 FT DISULFID 595 617 FT DISULFID 620 628 FT DISULFID 624 636 FT MOD_RES 678 678 PHOSPHORYLATION (BY PKC). FT MOD_RES 1092 1092 PHOSPHORYLATION (AUTO-). FT MOD_RES 1110 1110 PHOSPHORYLATION (AUTO-). FT MOD_RES 1172 1172 PHOSPHORYLATION (AUTO-). FT MOD_RES 1197 1197 PHOSPHORYLATION (AUTO-) (MAJOR). FT CARBOHYD 56 56 N-LINKED (GLCNAC...) (COMPLEX). FT /FTId=CAR_000227. FT CARBOHYD 128 128 N-LINKED (GLCNAC...). FT CARBOHYD 175 175 N-LINKED (GLCNAC...). FT CARBOHYD 352 352 N-LINKED (GLCNAC...). FT CARBOHYD 361 361 N-LINKED (GLCNAC...). FT CARBOHYD 413 413 N-LINKED (GLCNAC...). FT CARBOHYD 444 444 N-LINKED (GLCNAC...). FT CARBOHYD 528 528 N-LINKED (GLCNAC...). FT CARBOHYD 568 568 N-LINKED (GLCNAC...). FT CARBOHYD 603 603 N-LINKED (GLCNAC...). FT VARSPLIC 404 405 FL -> LS (in isoform 2). FT /FTId=VSP_002887. FT VARSPLIC 406 1210 Missing (in isoform 2). FT /FTId=VSP_002888. FT VARSPLIC 628 705 CTGPGLEGCPTNGPKIPSIATGMVGALLLLLVVALGIGLFM FT RRRHIVRKRTLRRLLQERELVEPLTPSGEAPNQALLR -> FT PGNESLKAMLFCLFKLSSCNQSNDGSVSHQSGSPAAQESCL FT GWIPSLLPSEFQLGWGGCSHLHAWPSASVIITASSCH (in FT isoform 3). FT /FTId=VSP_002889. FT VARSPLIC 706 1210 Missing (in isoform 3). FT /FTId=VSP_002890. FT VARSPLIC 628 628 C -> S (in isoform 4). FT /FTId=VSP_002891. FT VARSPLIC 629 1210 Missing (in isoform 4). FT /FTId=VSP_002892. FT CONFLICT 540 540 N -> K (IN REF. 1). SQ SEQUENCE 1210 AA; 134277 MW; D8A2A50B4EFB6ED2 CRC64; MRPSGTAGAA LLALLAALCP ASRALEEKKV CQGTSNKLTQ LGTFEDHFLS LQRMFNNCEV VLGNLEITYV QRNYDLSFLK TIQEVAGYVL IALNTVERIP LENLQIIRGN MYYENSYALA VLSNYDANKT GLKELPMRNL QEILHGAVRF SNNPALCNVE SIQWRDIVSS DFLSNMSMDF QNHLGSCQKC DPSCPNGSCW GAGEENCQKL TKIICAQQCS GRCRGKSPSD CCHNQCAAGC TGPRESDCLV CRKFRDEATC KDTCPPLMLY NPTTYQMDVN PEGKYSFGAT CVKKCPRNYV VTDHGSCVRA CGADSYEMEE DGVRKCKKCE GPCRKVCNGI GIGEFKDSLS INATNIKHFK NCTSISGDLH ILPVAFRGDS FTHTPPLDPQ ELDILKTVKE ITGFLLIQAW PENRTDLHAF ENLEIIRGRT KQHGQFSLAV VSLNITSLGL RSLKEISDGD VIISGNKNLC YANTINWKKL FGTSGQKTKI ISNRGENSCK ATGQVCHALC SPEGCWGPEP RDCVSCRNVS RGRECVDKCN LLEGEPREFV ENSECIQCHP ECLPQAMNIT CTGRGPDNCI QCAHYIDGPH CVKTCPAGVM GENNTLVWKY ADAGHVCHLC HPNCTYGCTG PGLEGCPTNG PKIPSIATGM VGALLLLLVV ALGIGLFMRR RHIVRKRTLR RLLQERELVE PLTPSGEAPN QALLRILKET EFKKIKVLGS GAFGTVYKGL WIPEGEKVKI PVAIKELREA TSPKANKEIL DEAYVMASVD NPHVCRLLGI CLTSTVQLIT QLMPFGCLLD YVREHKDNIG SQYLLNWCVQ IAKGMNYLED RRLVHRDLAA RNVLVKTPQH VKITDFGLAK LLGAEEKEYH AEGGKVPIKW MALESILHRI YTHQSDVWSY GVTVWELMTF GSKPYDGIPA SEISSILEKG ERLPQPPICT IDVYMIMVKC WMIDADSRPK FRELIIEFSK MARDPQRYLV IQGDERMHLP SPTDSNFYRA LMDEEDMDDV VDADEYLIPQ QGFFSSPSTS RTPLLSSLSA TSNNSTVACI DRNGLQSCPI KEDSFLQRYS SDPTGALTED SIDDTFLPVP EYINQSVPKR PAGSVQNPVY HNQPLNPAPS RDPHYQDPHS TAVGNPEYLN TVQPTCVNST FDSPAHWAQK GSHQISLDNP DYQQDFFPKE AKPNGIFKGS TAENAEYLRV APQSSEFIGA //