8.A.23.1.46
Epidermal growth factor receptor, EGFR, of 1210 aas and two TMSs, one N-terminal and one at residue 655. The CryoEM 3-d structure is available (Cai et al. 2022). Receptor tyrosine kinase binding ligands of the EGF family activate several signaling cascades to convert extracellular cues into
appropriate cellular responses (Runkle et al. 2016). Two FDA-approved EGFR inhibitor drugs
(lapatinib and afatinib) inside living cells and the changes in their
cellular uptake upon the addition of organic cation transporter
inhibitors have been reported (Wong et al. 2024). EGFR, a transmembrane protein commonly targeted by tyrosine kinase inhibitors (TKIs) as a front-line therapy for patients with many cancers including nonsmall cell lung cancer (NSCLC). Effective treatment requires efficient intracellular drug uptake and target binding, but despite the recent success in the development of new TKI drugs, TKI drugs are sequestered in lysosomes. Two Food and Drug Administration-approved EGFR inhibitory drugs (lapatinib and afatinib) inside living cells and the changes in their cellular uptake by facilitated diffusion upon the addition of organic cation transporter inhibitors has been recorded (Wong et al. 2024). Head and neck squamous cell carcinoma cells show increased EGFR levels as well as higher GLUT-1 and P-cadherin levels (van Schaik et al. 2024).
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| Accession Number: | P00533 |
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| Protein Name: | Epidermal growth factor receptor |
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| Length: | 1210 |
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| Molecular Weight: | 134277.00 |
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| Species: | Homo sapiens (Human) [9606] |
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| Number of TMSs: | 2 |
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| Location1 / Topology2 / Orientation3: |
Secreted1 |
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| Substrate |
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1: MRPSGTAGAA LLALLAALCP ASRALEEKKV CQGTSNKLTQ LGTFEDHFLS LQRMFNNCEV
61: VLGNLEITYV QRNYDLSFLK TIQEVAGYVL IALNTVERIP LENLQIIRGN MYYENSYALA
121: VLSNYDANKT GLKELPMRNL QEILHGAVRF SNNPALCNVE SIQWRDIVSS DFLSNMSMDF
181: QNHLGSCQKC DPSCPNGSCW GAGEENCQKL TKIICAQQCS GRCRGKSPSD CCHNQCAAGC
241: TGPRESDCLV CRKFRDEATC KDTCPPLMLY NPTTYQMDVN PEGKYSFGAT CVKKCPRNYV
301: VTDHGSCVRA CGADSYEMEE DGVRKCKKCE GPCRKVCNGI GIGEFKDSLS INATNIKHFK
361: NCTSISGDLH ILPVAFRGDS FTHTPPLDPQ ELDILKTVKE ITGFLLIQAW PENRTDLHAF
421: ENLEIIRGRT KQHGQFSLAV VSLNITSLGL RSLKEISDGD VIISGNKNLC YANTINWKKL
481: FGTSGQKTKI ISNRGENSCK ATGQVCHALC SPEGCWGPEP RDCVSCRNVS RGRECVDKCN
541: LLEGEPREFV ENSECIQCHP ECLPQAMNIT CTGRGPDNCI QCAHYIDGPH CVKTCPAGVM
601: GENNTLVWKY ADAGHVCHLC HPNCTYGCTG PGLEGCPTNG PKIPSIATGM VGALLLLLVV
661: ALGIGLFMRR RHIVRKRTLR RLLQERELVE PLTPSGEAPN QALLRILKET EFKKIKVLGS
721: GAFGTVYKGL WIPEGEKVKI PVAIKELREA TSPKANKEIL DEAYVMASVD NPHVCRLLGI
781: CLTSTVQLIT QLMPFGCLLD YVREHKDNIG SQYLLNWCVQ IAKGMNYLED RRLVHRDLAA
841: RNVLVKTPQH VKITDFGLAK LLGAEEKEYH AEGGKVPIKW MALESILHRI YTHQSDVWSY
901: GVTVWELMTF GSKPYDGIPA SEISSILEKG ERLPQPPICT IDVYMIMVKC WMIDADSRPK
961: FRELIIEFSK MARDPQRYLV IQGDERMHLP SPTDSNFYRA LMDEEDMDDV VDADEYLIPQ
1021: QGFFSSPSTS RTPLLSSLSA TSNNSTVACI DRNGLQSCPI KEDSFLQRYS SDPTGALTED
1081: SIDDTFLPVP EYINQSVPKR PAGSVQNPVY HNQPLNPAPS RDPHYQDPHS TAVGNPEYLN
1141: TVQPTCVNST FDSPAHWAQK GSHQISLDNP DYQQDFFPKE AKPNGIFKGS TAENAEYLRV
1201: APQSSEFIGA