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, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1997, sequence version 2. DT 04-APR-2006, entry version 92. DE Epidermal growth factor receptor precursor (EC 2.7.10.1) (Receptor DE tyrosine-protein kinase ErbB-1). GN Name=EGFR; Synonyms=ERBB1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE (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 NUCLEOTIDE SEQUENCE (ISOFORM 2). RC TISSUE=Placenta; RX MEDLINE=95382957; PubMed=7654368; DOI=10.1262/jrd.41.149; 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 NUCLEOTIDE SEQUENCE (ISOFORM 2). RC TISSUE=Placenta; RX MEDLINE=97078686; PubMed=8918811; DOI=10.1093/nar/24.20.4050; 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 NUCLEOTIDE SEQUENCE (ISOFORM 2). RC TISSUE=Placenta; RX MEDLINE=97256547; PubMed=9103388; DOI=10.1006/gyno.1996.4526; 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 NUCLEOTIDE SEQUENCE (ISOFORMS 3 AND 4). RC TISSUE=Placenta; RX MEDLINE=21100872; PubMed=11161793; DOI=10.1006/geno.2000.6341; 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 NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLN-98; ARG-266; RP LYS-521; ILE-674; GLY-962 AND PRO-988. RA Livingston R.J., Rieder M.J., Chung M.-W., Ritchie T.K., Olson A.N., RA Nguyen C.P., Nguyen D.A., Poel C.L., Robertson P.D., Schackwitz W.S., RA Sherwood J.K., Sherwood A.M., Leithauser B.J., Nickerson D.A.; RT "NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department RT of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu)."; RL Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE OF 575-687. 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 [8] RP NUCLEOTIDE SEQUENCE OF 713-924. RX MEDLINE=84196372; PubMed=6326261; RA Lin C.R., Chen W.S., Kruiger W., Stolarsky L.S., Weber W., Evans R.M., RA 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 [9] RP NUCLEOTIDE SEQUENCE OF 150-962. 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 [10] RP NUCLEOTIDE SEQUENCE OF 1028-1210. 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 [11] RP NUCLEOTIDE SEQUENCE OF 1-29. 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 [12] RP NUCLEOTIDE SEQUENCE OF 1-29. 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 [13] RP NUCLEOTIDE SEQUENCE OF 1-29. 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 [14] RP NUCLEOTIDE SEQUENCE OF 25-49. RX MEDLINE=84172183; PubMed=6324343; RA Weber W., Gill G.N., Spiess J.; RT "Production of an epidermal growth factor receptor-related protein."; RL Science 224:294-297(1984). RN [15] RP PROTEIN SEQUENCE OF 540. RA Kohda D.; RL Submitted (SEP-1997) to Swiss-Prot. RN [16] RP PROTEIN SEQUENCE OF 687-705; 986-998; 1000-1023; 1026-1030 AND RP 1068-1077, AND PHOSPHORYLATION SITES THR-693; SER-695; SER-1070 AND RP SER-1071. RX MEDLINE=88330814; PubMed=3138233; RA Heisermann G.J., Gill G.N.; RT "Epidermal growth factor receptor threonine and serine residues RT phosphorylated in vivo."; RL J. Biol. Chem. 263:13152-13158(1988). RN [17] RP PROTEIN SEQUENCE OF 25-39. RX PubMed=15340161; DOI=10.1110/ps.04682504; RA Zhang Z., Henzel W.J.; RT "Signal peptide prediction based on analysis of experimentally RT verified cleavage sites."; RL Protein Sci. 13:2819-2824(2004). RN [18] RP PROTEIN SEQUENCE OF 740-744 AND 746-747. RX MEDLINE=85182650; PubMed=2985580; RA Russo M.W., Lukas T.J., Cohen S., Staros J.V.; RT "Identification of residues in the nucleotide binding site of the RT epidermal growth factor receptor/kinase."; RL J. Biol. Chem. 260:5205-5208(1985). RN [19] 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 [20] RP LIGAND BINDING. RX MEDLINE=90003233; PubMed=2790960; DOI=10.1016/0092-8674(89)90867-2; RA Chen W.S., Lazar C.S., Lund K.A., Welsh J.B., Chang C.P., Walton G.M., RA Der C.J., Wiley H.S., Gill G.N., Rosenfeld M.G.; RT "Functional independence of the epidermal growth factor receptor from RT a domain required for ligand-induced internalization and calcium RT regulation."; RL Cell 59:33-43(1989). RN [21] 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 [22] 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 [23] 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 [24] RP PHOSPHORYLATION SITE THR-693. RX PubMed=15302935; DOI=10.1073/pnas.0404720101; RA Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., RA Li J., Cohn M.A., Cantley L.C., Gygi S.P.; RT "Large-scale characterization of HeLa cell nuclear phosphoproteins."; RL Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004). RN [25] RP PARTIAL PROTEIN SEQUENCE, AND DISULFIDE BONDS. RX MEDLINE=98225196; PubMed=9556602; DOI=10.1074/jbc.273.18.11150; 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 [26] RP REVIEW. RX MEDLINE=87297456; PubMed=3039909; RX DOI=10.1146/annurev.bi.56.070187.004313; RA Carpenter G.; RT "Receptors for epidermal growth factor and other polypeptide RT mitogens."; RL Annu. Rev. Biochem. 56:881-914(1987). RN [27] RP INTERACTION WITH CBL. RX PubMed=7657591; DOI=10.1074/jbc.270.35.20242; RA Galisteo M.L., Dikic I., Batzer A.G., Langdon W.Y., Schlessinger J.; RT "Tyrosine phosphorylation of the c-cbl proto-oncogene protein product RT and association with epidermal growth factor (EGF) receptor upon EGF RT stimulation."; RL J. Biol. Chem. 270:20242-20245(1995). RN [28] RP IDENTIFICATION IN A COMPLEX WITH PIK3C2A AND ERBB2, IDENTIFICATION IN RP A COMPLEX WITH PIK3C2B AND ERBB2, INTERACTION WITH PIK3C2B, AND RP MUTAGENESIS OF TYR-1016; TYR-1092; TYR-1110; TYR-1172 AND TYR-1197. RX PubMed=10805725; DOI=10.1128/MCB.20.11.3817-3830.2000; RA Arcaro A., Zvelebil M.J., Wallasch C., Ullrich A., Waterfield M.D., RA Domin J.; RT "Class II phosphoinositide 3-kinases are downstream targets of RT activated polypeptide growth factor receptors."; RL Mol. Cell. Biol. 20:3817-3830(2000). RN [29] RP INTERACTION WITH RIPK1. RX MEDLINE=21153697; PubMed=11116146; DOI=10.1074/jbc.M008458200; RA Habib A.A., Chatterjee S., Park S.-K., Ratan R.R., Lefebvre S., RA Vartanian T.; RT "The epidermal growth factor receptor engages receptor interacting RT protein and nuclear factor-kappa B (NF-kappa B)-inducing kinase to RT activate NF-kappa B. Identification of a novel receptor-tyrosine RT kinase signalosome."; RL J. Biol. Chem. 276:8865-8874(2001). RN [30] RP PHOSPHORYLATION SITE TYR-978, AND MASS SPECTROMETRY. RX PubMed=16097034; DOI=10.1002/pmic.200401217; RA Gevaert K., Staes A., Van Damme J., De Groot S., Hugelier K., RA Demol H., Martens L., Goethals M., Vandekerckhove J.; RT "Global phosphoproteome analysis on human HepG2 hepatocytes using RT reversed-phase diagonal LC."; RL Proteomics 5:3589-3599(2005). RN [31] RP VARIANTS LUNG CANCER SER-719 AND ARG-858. RX PubMed=15118125; DOI=10.1126/science.1099314; RA Paez J.G., Janne P.A., Lee J.C., Tracy S., Greulich H., Gabriel S., RA Herman P., Kaye F.J., Lindeman N., Boggon T.J., Naoki K., Sasaki H., RA Fujii Y., Eck M.J., Sellers W.R., Johnson B.E., Meyerson M.; RT "EGFR mutations in lung cancer: correlation with clinical response to RT gefitinib therapy."; RL Science 304:1497-1500(2004). 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]-L-tyrosine = ADP + a CC [protein]-L-tyrosine phosphate. CC -!- SUBUNIT: Binds RIPK1. CBL interacts with the autophosphorylated C- CC terminal tail of the EGF receptor. Part of a complex with ERBB2 CC and either PIK3C2A or PIK3C2B. The autophoshorylated form CC interacts with PIK3C2B, maybe indirectly. CC -!- INTERACTION: CC P22681:CBL; NbExp=1; IntAct=EBI-297353, EBI-518228; CC P22682:Cbl (xeno); NbExp=1; IntAct=EBI-297353, EBI-640919; CC P13987:CD59; NbExp=1; IntAct=EBI-297353, EBI-297972; CC P01133:EGF; NbExp=1; IntAct=EBI-297353, EBI-640857; CC P04626:ERBB2; NbExp=1; IntAct=EBI-297353, EBI-641062; CC P21860:ERBB3; NbExp=2; IntAct=EBI-297353, EBI-720706; CC Q15303:ERBB4; NbExp=2; IntAct=EBI-297353, EBI-80371; CC P62993:GRB2; NbExp=2; IntAct=EBI-297353, EBI-401755; CC O00750:PIK3C2B; NbExp=4; IntAct=EBI-297353, EBI-641107; CC P98083:Shc1 (xeno); NbExp=1; IntAct=EBI-297353, EBI-300201; CC P63104:YWHAZ; NbExp=1; IntAct=EBI-297353, EBI-347088; 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 -!- PTM: Phosphorylation of Ser-695 is partial and occurs only if Thr- CC 693 is phosphorylated. CC -!- DISEASE: Defects in EGFR are associated with lung cancer. 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 Tyr protein kinase family. EGF receptor CC subfamily. 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; -; mRNA. DR EMBL; U95089; AAB53063.1; -; mRNA. DR EMBL; U48722; AAC50802.1; -; mRNA. DR EMBL; U48723; AAC50804.1; -; Genomic_DNA. DR EMBL; U48724; AAC50796.1; -; Genomic_RNA. DR EMBL; U48725; AAC50797.1; -; Genomic_RNA. DR EMBL; U48726; AAC50798.1; -; Genomic_RNA. DR EMBL; U48727; AAC50799.1; -; Genomic_RNA. DR EMBL; U48728; AAC50800.1; -; Genomic_RNA. DR EMBL; U48729; AAC50801.1; -; Genomic_RNA. DR EMBL; AF288738; AAG35786.1; -; Genomic_DNA. DR EMBL; AF288738; AAG35787.1; -; Genomic_DNA. DR EMBL; AF288738; AAG35788.1; -; Genomic_DNA. DR EMBL; AF288738; AAG35789.1; -; Genomic_DNA. DR EMBL; AF288738; AAG35790.1; -; Genomic_DNA. DR EMBL; AY588246; AAS83109.1; -; Genomic_DNA. DR EMBL; AF277897; AAK01080.1; -; mRNA. DR EMBL; AF125253; AAG43240.1; -; mRNA. DR EMBL; AF125539; AAG43243.1; -; Genomic_DNA. DR EMBL; AF125538; AAG43243.1; JOINED; Genomic_DNA. DR EMBL; X06370; CAA29668.1; -; Genomic_DNA. DR EMBL; X00663; CAA25282.1; -; mRNA. DR EMBL; M38425; AAA63171.1; -; Genomic_DNA. DR EMBL; M11234; AAA52370.1; -; Genomic_DNA. DR PIR; A00641; GQHUE. DR UniGene; Hs.488293; -. DR PDB; 1DNQ; Model; A=25-336. DR PDB; 1DNR; Model; A=337-645. DR PDB; 1IVO; X-ray; A/B=25-646. DR PDB; 1M14; X-ray; A=695-1022. DR PDB; 1M17; X-ray; A=695-1022. DR PDB; 1MOX; X-ray; A/B=25-525. DR PDB; 1NQL; X-ray; A=25-642. DR PDB; 1XKK; X-ray; A=695-1022. DR PDB; 1Z9I; NMR; A=669-721. DR IntAct; P00533; -. DR GlycoSuiteDB; P00533; -. DR SWISS-2DPAGE; P00533; HUMAN. DR Ensembl; ENSG00000146648; Homo sapiens. DR HGNC; HGNC:3236; EGFR. DR MIM; 131550; gene. DR GO; GO:0005768; C:endosome; IDA. DR GO; GO:0005615; C:extracellular space; NAS. DR GO; GO:0005634; C:nucleus; IDA. DR GO; GO:0005886; C:plasma membrane; IDA. DR GO; GO:0051015; F:actin filament binding; IDA. DR GO; GO:0003690; F:double-stranded DNA binding; NAS. DR GO; GO:0005006; F:epidermal growth factor receptor activity; IDA. DR GO; GO:0004710; F:MAP/ERK kinase kinase activity; NAS. DR GO; GO:0005515; F:protein binding; IPI. DR GO; GO:0046982; F:protein heterodimerization activity; IDA. DR GO; GO:0004713; F:protein-tyrosine kinase activity; IMP. DR GO; GO:0004888; F:transmembrane receptor activity; IDA. DR GO; GO:0043006; P:calcium-dependent phospholipase A2 activation; TAS. DR GO; GO:0008283; P:cell proliferation; TAS. DR GO; GO:0007166; P:cell surface receptor linked signal transdu...; IDA. DR GO; GO:0016337; P:cell-cell adhesion; IMP. DR GO; GO:0007173; P:epidermal growth factor receptor signaling ...; IDA. DR GO; GO:0001503; P:ossification; NAS. DR GO; GO:0007202; P:phospholipase C activation; TAS. DR GO; GO:0030335; P:positive regulation of cell migration; IMP. DR GO; GO:0050679; P:positive regulation of epithelial cell prol...; IDA. DR GO; GO:0043406; P:positive regulation of MAPK activity; IDA. DR GO; GO:0045429; P:positive regulation of nitric oxide biosynt...; IDA. DR GO; GO:0042327; P:positive regulation of phosphorylation; IDA. DR GO; GO:0051205; P:protein insertion into membrane; TAS. DR GO; GO:0050999; P:regulation of nitric-oxide synthase activity; IDA. DR GO; GO:0050730; P:regulation of peptidyl-tyrosine phosphoryla...; IMP. DR GO; GO:0006950; P:response to stress; NAS. DR InterPro; IPR000494; EGF_rcpt_L. DR InterPro; IPR006211; Furin-like. DR InterPro; IPR006212; Furin_repeat. DR InterPro; IPR009030; Growth_fac_rcpt. DR InterPro; IPR011009; Kinase_like. DR InterPro; IPR000719; Prot_kinase. DR InterPro; IPR001245; Tyr_pkinase. DR InterPro; IPR008266; Tyr_pkinase_AS. DR Pfam; PF00757; Furin-like; 1. DR Pfam; PF07714; Pkinase_Tyr; 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; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1. KW 3D-structure; Alternative splicing; Anti-oncogene; ATP-binding; KW Cell cycle; Direct protein sequencing; Disease mutation; Glycoprotein; KW Kinase; Membrane; Nucleotide-binding; Phosphorylation; Polymorphism; KW Receptor; Repeat; Signal; Transferase; Transmembrane; KW Tyrosine-protein kinase. FT SIGNAL 1 24 FT CHAIN 25 1210 Epidermal growth factor receptor. FT /FTId=PRO_0000016665. FT TOPO_DOM 25 645 Extracellular (Potential). FT TRANSMEM 646 668 Potential. FT TOPO_DOM 669 1210 Cytoplasmic (Potential). FT REPEAT 75 300 Approximate. FT REPEAT 390 600 Approximate. FT DOMAIN 712 979 Protein kinase. FT NP_BIND 718 726 ATP (By similarity). FT COMPBIAS 1025 1071 Ser-rich. FT ACT_SITE 837 837 By similarity. FT BINDING 745 745 ATP (By similarity). FT SITE 1016 1016 Important for interaction with PIK3C2B. FT MOD_RES 678 678 Phosphothreonine (by PKC). FT MOD_RES 693 693 Phosphothreonine. FT MOD_RES 695 695 Phosphoserine (partial). FT MOD_RES 978 978 Phosphotyrosine. FT MOD_RES 1070 1070 Phosphoserine. FT MOD_RES 1071 1071 Phosphoserine. FT MOD_RES 1092 1092 Phosphotyrosine (by autocatalysis) FT (partial). FT MOD_RES 1110 1110 Phosphotyrosine (by autocatalysis) FT (partial). FT MOD_RES 1172 1172 Phosphotyrosine (by autocatalysis) FT (partial). FT MOD_RES 1197 1197 Phosphotyrosine (by autocatalysis). FT CARBOHYD 56 56 N-linked (GlcNAc...) (complex); atypical. 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 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 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 628 628 C -> S (in isoform 4). FT /FTId=VSP_002891. FT VARSPLIC 629 1210 Missing (in isoform 4). FT /FTId=VSP_002892. FT VARSPLIC 706 1210 Missing (in isoform 3). FT /FTId=VSP_002890. FT VARIANT 98 98 R -> Q. FT /FTId=VAR_019293. FT VARIANT 266 266 P -> R. FT /FTId=VAR_019294. FT VARIANT 521 521 R -> K (in dbSNP:11543848). FT /FTId=VAR_019295. FT VARIANT 674 674 V -> I. FT /FTId=VAR_019296. FT VARIANT 719 719 G -> S (in lung cancer; somatic FT mutation). FT /FTId=VAR_019297. FT VARIANT 858 858 L -> R (in lung cancer; somatic FT mutation). FT /FTId=VAR_019298. FT VARIANT 962 962 R -> G. FT /FTId=VAR_019299. FT VARIANT 988 988 H -> P. FT /FTId=VAR_019300. FT MUTAGEN 1016 1016 Y->F: 50% decrease in interaction with FT PIK3C2B. 65% decrease in interaction with FT PIK3C2B; when associated with F-1197. FT Abolishes interaction with PIK3C2B; when FT associated with F-1197 and F-1092. FT MUTAGEN 1092 1092 Y->F: No change in interaction with FT PIK3C2B. Abolishes interaction with FT PIK3C2B; when associated with F-1197 and FT F-1016. FT MUTAGEN 1110 1110 Y->F: No change in interaction with FT PIK3C2B. FT MUTAGEN 1172 1172 Y->F: No change in interaction with FT PIK3C2B. FT MUTAGEN 1197 1197 Y->F: No change in interaction with FT PIK3C2B. 65% decrease in interaction with FT PIK3C2B; when associated with F-1016. FT Abolishes interaction with PIK3C2B; when FT associated with F-1092 and F-1016. FT CONFLICT 540 540 N -> K (in Ref. 1). FT STRAND 30 31 FT STRAND 34 34 FT TURN 37 38 FT STRAND 40 40 FT STRAND 42 43 FT HELIX 44 55 FT TURN 56 57 FT STRAND 59 68 FT TURN 72 73 FT HELIX 77 81 FT STRAND 84 87 FT STRAND 89 93 FT STRAND 97 98 FT TURN 102 103 FT STRAND 106 107 FT STRAND 110 111 FT STRAND 113 113 FT TURN 114 116 FT STRAND 117 122 FT STRAND 125 129 FT STRAND 131 131 FT STRAND 134 134 FT TURN 138 139 FT STRAND 142 143 FT STRAND 145 152 FT TURN 154 155 FT STRAND 158 158 FT HELIX 159 161 FT HELIX 164 166 FT TURN 167 167 FT STRAND 168 168 FT HELIX 170 173 FT TURN 174 175 FT STRAND 183 184 FT TURN 192 193 FT STRAND 194 194 FT HELIX 195 197 FT STRAND 199 203 FT HELIX 204 206 FT STRAND 207 207 FT STRAND 211 214 FT TURN 217 218 FT STRAND 220 221 FT STRAND 223 227 FT TURN 228 229 FT STRAND 230 231 FT TURN 234 235 FT STRAND 236 245 FT TURN 246 247 FT STRAND 248 256 FT TURN 257 258 FT STRAND 259 263 FT STRAND 267 270 FT TURN 272 274 FT STRAND 275 279 FT TURN 281 282 FT STRAND 285 287 FT TURN 288 289 FT STRAND 290 294 FT TURN 297 298 FT STRAND 300 301 FT TURN 303 304 FT STRAND 305 310 FT STRAND 313 314 FT STRAND 318 318 FT STRAND 320 323 FT STRAND 325 325 FT STRAND 336 338 FT STRAND 340 340 FT TURN 341 341 FT STRAND 342 342 FT HELIX 343 345 FT TURN 346 347 FT STRAND 350 351 FT TURN 353 354 FT HELIX 355 357 FT TURN 358 361 FT STRAND 363 371 FT TURN 373 373 FT HELIX 374 377 FT STRAND 379 379 FT HELIX 380 382 FT TURN 383 383 FT STRAND 384 384 FT HELIX 389 397 FT STRAND 400 403 FT STRAND 405 408 FT TURN 412 413 FT STRAND 415 416 FT HELIX 418 420 FT TURN 421 422 FT STRAND 425 426 FT STRAND 429 430 FT STRAND 432 432 FT TURN 433 435 FT STRAND 436 442 FT STRAND 446 447 FT TURN 451 452 FT STRAND 455 456 FT STRAND 458 464 FT TURN 467 468 FT STRAND 471 471 FT HELIX 472 474 FT STRAND 475 475 FT HELIX 477 480 FT STRAND 481 481 FT STRAND 483 483 FT TURN 484 485 FT STRAND 488 489 FT STRAND 492 494 FT HELIX 496 501 FT TURN 502 503 FT TURN 508 509 FT STRAND 512 513 FT STRAND 515 519 FT HELIX 520 522 FT STRAND 523 523 FT TURN 532 533 FT STRAND 534 537 FT STRAND 540 543 FT STRAND 545 546 FT STRAND 548 557 FT TURN 560 561 FT STRAND 562 562 FT TURN 566 567 FT STRAND 568 568 FT STRAND 571 575 FT TURN 576 577 FT STRAND 579 587 FT TURN 588 589 FT STRAND 590 594 FT STRAND 597 600 FT STRAND 602 611 FT TURN 613 614 FT STRAND 616 619 FT TURN 622 623 FT STRAND 625 626 FT STRAND 629 632 FT TURN 633 635 FT STRAND 636 636 FT STRAND 704 706 FT TURN 709 711 FT STRAND 712 720 FT STRAND 722 731 FT STRAND 740 747 FT TURN 755 755 FT HELIX 756 768 FT TURN 772 773 FT STRAND 774 774 FT STRAND 777 791 FT TURN 794 795 FT STRAND 797 797 FT HELIX 798 804 FT TURN 805 805 FT STRAND 806 808 FT HELIX 811 830 FT TURN 831 832 FT STRAND 836 836 FT HELIX 840 842 FT STRAND 843 847 FT TURN 848 849 FT STRAND 850 853 FT STRAND 857 857 FT HELIX 858 861 FT TURN 862 865 FT TURN 878 880 FT STRAND 881 881 FT HELIX 883 888 FT HELIX 893 908 FT TURN 909 910 FT STRAND 911 911 FT TURN 914 917 FT STRAND 918 918 FT HELIX 920 929 FT TURN 930 930 FT TURN 937 938 FT STRAND 939 939 FT HELIX 941 950 FT TURN 951 951 FT STRAND 953 954 FT HELIX 955 957 FT STRAND 958 958 FT HELIX 961 973 FT STRAND 974 974 FT HELIX 975 978 FT STRAND 979 979 FT TURN 982 986 FT HELIX 996 1002 FT HELIX 1013 1016 FT TURN 1017 1017 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 //