EKS-HOS-00304

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-HOS-00304

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
TK/EGFR	498.4	2.0E-149	667	924	258

Status

Reviewed

Ensembl Protein

ENSP00000415559

UniProt Accession

P00533; O00688; O00732; P06268; Q14225; Q68GS5; Q92795; Q9BZS2; Q9GZX1; Q9H2C9; Q9H3C9; Q9UMD7; Q9UMD8; Q9UMG5;

Protein Name

Epidermal growth factor receptor

Protein Synonyms/Alias

Proto-oncogene c-ErbB-1; Receptor tyrosine-protein kinase erbB-1;

Gene Name

EGFR

Gene Synonyms/Alias

EGFR; ERBB, ERBB1, HER1;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSG00000146648	ENSP00000275493	ENST00000275493
ENSG00000146648	ENSP00000415559	ENST00000455089
ENSG00000146648	ENSP00000395243	ENST00000454757
ENSG00000146648	ENSP00000413843	ENST00000420316
ENSG00000146648	ENSP00000345973	ENST00000344576
ENSG00000146648	ENSP00000410031	ENST00000442591
ENSG00000146648	ENSP00000342376	ENST00000342916
ENSG00000146648	ENSP00000413354	ENST00000450046

Organism

Homo sapiens

Functional Description

Receptor tyrosine kinase binding ligands of the EGFfamily and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TGFA/TGF-alpha, amphiregulin, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at least 4 major downstream signaling cascades including the RAS- RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules. May also activate the NF-kappa-B signaling cascade. Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling. Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin. Isoform 2 may act as an antagonist of EGF action.

Protein Length

1091

Protein Sequence
(FASTA)

MRPSGTAGAA LLALLAALCP ASRALEEKKV CQGTSNKLTQ LGTFEDHFLS LQRMFNNCEV 60

VLGNLEITYV QRNYDLSFLK TIQEVAGYVL IALNTVERIP LENLQIIRGN MYYENSYALA 120

VLSNYDANKT GLKELPMRNL QGQKCDPSCP NGSCWGAGEE NCQKLTKIIC AQQCSGRCRG 180

KSPSDCCHNQ CAAGCTGPRE SDCLVCRKFR DEATCKDTCP PLMLYNPTTY QMDVNPEGKY 240

SFGATCVKKC PRNYVVTDHG SCVRACGADS YEMEEDGVRK CKKCEGPCRK VCNGIGIGEF 300

KDSLSINATN IKHFKNCTSI SGDLHILPVA FRGDSFTHTP PLDPQELDIL KTVKEITGFL 360

LIQAWPENRT DLHAFENLEI IRGRTKQHGQ FSLAVVSLNI TSLGLRSLKE ISDGDVIISG 420

NKNLCYANTI NWKKLFGTSG QKTKIISNRG ENSCKATGQV CHALCSPEGC WGPEPRDCVS 480

CRNVSRGREC VDKCNLLEGE PREFVENSEC IQCHPECLPQ AMNITCTGRG PDNCIQCAHY 540

IDGPHCVKTC PAGVMGENNT LVWKYADAGH VCHLCHPNCT YGCTGPGLEG CPTNGPKIPS 600

IATGMVGALL LLLVVALGIG LFMRRRHIVR KRTLRRLLQE RELVEPLTPS GEAPNQALLR 660

ILKETEFKKI KVLGSGAFGT VYKGLWIPEG EKVKIPVAIK ELREATSPKA NKEILDEAYV 720

MASVDNPHVC RLLGICLTST VQLITQLMPF GCLLDYVREH KDNIGSQYLL NWCVQIAKGM 780

NYLEDRRLVH RDLAARNVLV KTPQHVKITD FGLAKLLGAE EKEYHAEGGK VPIKWMALES 840

ILHRIYTHQS DVWSYGVTVW ELMTFGSKPY DGIPASEISS ILEKGERLPQ PPICTIDVYM 900

IMVKCWMIDA DSRPKFRELI IEFSKMARDP QRYLVIQGDE RMHLPSPTDS NFYRALMDEE 960

DMDDVVDADE YLIPQQGFFS SPSTSRTPLL SSLSATSNNS TVACIDRNGL QSCPIKEDSF 1020

LQRYSSDPTG ALTEDSIDDT FLPVPGEWLV WKQSCSSTSS THSAAASLQC PSQVLPPASP 1080

EGETVADLQT Q 1091

Nucleotide Sequence
(FASTA)

ATGCGACCCT CCGGGACGGC CGGGGCAGCG CTCCTGGCGC TGCTGGCTGC GCTCTGCCCG 60

GCGAGTCGGG CTCTGGAGGA AAAGAAAGTT TGCCAAGGCA CGAGTAACAA GCTCACGCAG 120

TTGGGCACTT TTGAAGATCA TTTTCTCAGC CTCCAGAGGA TGTTCAATAA CTGTGAGGTG 180

GTCCTTGGGA ATTTGGAAAT TACCTATGTG CAGAGGAATT ATGATCTTTC CTTCTTAAAG 240

ACCATCCAGG AGGTGGCTGG TTATGTCCTC ATTGCCCTCA ACACAGTGGA GCGAATTCCT 300

TTGGAAAACC TGCAGATCAT CAGAGGAAAT ATGTACTACG AAAATTCCTA TGCCTTAGCA 360

GTCTTATCTA ACTATGATGC AAATAAAACC GGACTGAAGG AGCTGCCCAT GAGAAATTTA 420

CAGGGCCAAA AGTGTGATCC AAGCTGTCCC AATGGGAGCT GCTGGGGTGC AGGAGAGGAG 480

AACTGCCAGA AACTGACCAA AATCATCTGT GCCCAGCAGT GCTCCGGGCG CTGCCGTGGC 540

AAGTCCCCCA GTGACTGCTG CCACAACCAG TGTGCTGCAG GCTGCACAGG CCCCCGGGAG 600

AGCGACTGCC TGGTCTGCCG CAAATTCCGA GACGAAGCCA CGTGCAAGGA CACCTGCCCC 660

CCACTCATGC TCTACAACCC CACCACGTAC CAGATGGATG TGAACCCCGA GGGCAAATAC 720

AGCTTTGGTG CCACCTGCGT GAAGAAGTGT CCCCGTAATT ATGTGGTGAC AGATCACGGC 780

TCGTGCGTCC GAGCCTGTGG GGCCGACAGC TATGAGATGG AGGAAGACGG CGTCCGCAAG 840

TGTAAGAAGT GCGAAGGGCC TTGCCGCAAA GTGTGTAACG GAATAGGTAT TGGTGAATTT 900

AAAGACTCAC TCTCCATAAA TGCTACGAAT ATTAAACACT TCAAAAACTG CACCTCCATC 960

AGTGGCGATC TCCACATCCT GCCGGTGGCA TTTAGGGGTG ACTCCTTCAC ACATACTCCT 1020

CCTCTGGATC CACAGGAACT GGATATTCTG AAAACCGTAA AGGAAATCAC AGGGTTTTTG 1080

CTGATTCAGG CTTGGCCTGA AAACAGGACG GACCTCCATG CCTTTGAGAA CCTAGAAATC 1140

ATACGCGGCA GGACCAAGCA ACATGGTCAG TTTTCTCTTG CAGTCGTCAG CCTGAACATA 1200

ACATCCTTGG GATTACGCTC CCTCAAGGAG ATAAGTGATG GAGATGTGAT AATTTCAGGA 1260

AACAAAAATT TGTGCTATGC AAATACAATA AACTGGAAAA AACTGTTTGG GACCTCCGGT 1320

CAGAAAACCA AAATTATAAG CAACAGAGGT GAAAACAGCT GCAAGGCCAC AGGCCAGGTC 1380

TGCCATGCCT TGTGCTCCCC CGAGGGCTGC TGGGGCCCGG AGCCCAGGGA CTGCGTCTCT 1440

TGCCGGAATG TCAGCCGAGG CAGGGAATGC GTGGACAAGT GCAACCTTCT GGAGGGTGAG 1500

CCAAGGGAGT TTGTGGAGAA CTCTGAGTGC ATACAGTGCC ACCCAGAGTG CCTGCCTCAG 1560

GCCATGAACA TCACCTGCAC AGGACGGGGA CCAGACAACT GTATCCAGTG TGCCCACTAC 1620

ATTGACGGCC CCCACTGCGT CAAGACCTGC CCGGCAGGAG TCATGGGAGA AAACAACACC 1680

CTGGTCTGGA AGTACGCAGA CGCCGGCCAT GTGTGCCACC TGTGCCATCC AAACTGCACC 1740

TACGGATGCA CTGGGCCAGG TCTTGAAGGC TGTCCAACGA ATGGGCCTAA GATCCCGTCC 1800

ATCGCCACTG GGATGGTGGG GGCCCTCCTC TTGCTGCTGG TGGTGGCCCT GGGGATCGGC 1860

CTCTTCATGC GAAGGCGCCA CATCGTTCGG AAGCGCACGC TGCGGAGGCT GCTGCAGGAG 1920

AGGGAGCTTG TGGAGCCTCT TACACCCAGT GGAGAAGCTC CCAACCAAGC TCTCTTGAGG 1980

ATCTTGAAGG AAACTGAATT CAAAAAGATC AAAGTGCTGG GCTCCGGTGC GTTCGGCACG 2040

GTGTATAAGG GACTCTGGAT CCCAGAAGGT GAGAAAGTTA AAATTCCCGT CGCTATCAAG 2100

GAATTAAGAG AAGCAACATC TCCGAAAGCC AACAAGGAAA TCCTCGATGA AGCCTACGTG 2160

ATGGCCAGCG TGGACAACCC CCACGTGTGC CGCCTGCTGG GCATCTGCCT CACCTCCACC 2220

GTGCAGCTCA TCACGCAGCT CATGCCCTTC GGCTGCCTCC TGGACTATGT CCGGGAACAC 2280

AAAGACAATA TTGGCTCCCA GTACCTGCTC AACTGGTGTG TGCAGATCGC AAAGGGCATG 2340

AACTACTTGG AGGACCGTCG CTTGGTGCAC CGCGACCTGG CAGCCAGGAA CGTACTGGTG 2400

AAAACACCGC AGCATGTCAA GATCACAGAT TTTGGGCTGG CCAAACTGCT GGGTGCGGAA 2460

GAGAAAGAAT ACCATGCAGA AGGAGGCAAA GTGCCTATCA AGTGGATGGC ATTGGAATCA 2520

ATTTTACACA GAATCTATAC CCACCAGAGT GATGTCTGGA GCTACGGGGT GACTGTTTGG 2580

GAGTTGATGA CCTTTGGATC CAAGCCATAT GACGGAATCC CTGCCAGCGA GATCTCCTCC 2640

ATCCTGGAGA AAGGAGAACG CCTCCCTCAG CCACCCATAT GTACCATCGA TGTCTACATG 2700

ATCATGGTCA AGTGCTGGAT GATAGACGCA GATAGTCGCC CAAAGTTCCG TGAGTTGATC 2760

ATCGAATTCT CCAAAATGGC CCGAGACCCC CAGCGCTACC TTGTCATTCA GGGGGATGAA 2820

AGAATGCATT TGCCAAGTCC TACAGACTCC AACTTCTACC GTGCCCTGAT GGATGAAGAA 2880

GACATGGACG ACGTGGTGGA TGCCGACGAG TACCTCATCC CACAGCAGGG CTTCTTCAGC 2940

AGCCCCTCCA CGTCACGGAC TCCCCTCCTG AGCTCTCTGA GTGCAACCAG CAACAATTCC 3000

ACCGTGGCTT GCATTGATAG AAATGGGCTG CAAAGCTGTC CCATCAAGGA AGACAGCTTC 3060

TTGCAGCGAT ACAGCTCAGA CCCCACAGGC GCCTTGACTG AGGACAGCAT AGACGACACC 3120

TTCCTCCCAG TGCCTGGTGA GTGGCTTGTC TGGAAACAGT CCTGCTCCTC AACCTCCTCG 3180

ACCCACTCAG CAGCAGCCAG TCTCCAGTGT CCAAGCCAGG TGCTCCCTCC AGCATCTCCA 3240

GAGGGGGAAA CAGTGGCAGA TTTGCAGACA CAGTGA 3276

Domain Profile

S: 1     lkklkvlGsGafGtvykGiwipegenvkipvaikvleektgkkankelldealvlasldh  60

         +kk+kvlGsGafGtvykG+wipege+vkipvaik+l+e+t++kanke+ldea+v+as+d+

Q: 667   FKKIKVLGSGAFGTVYKGLWIPEGEKVKIPVAIKELREATSPKANKEILDEAYVMASVDN  726

         59**********************************************************

S: 61    anlvrllglclsstlqlvtqllplGclldyvrehkdklGsqellnwcvqiakGmsyleek  120

         ++++rllg+cl+st+ql+tql+p+Gclldyvrehkd++Gsq+llnwcvqiakGm+yle++

Q: 727   PHVCRLLGICLTSTVQLITQLMPFGCLLDYVREHKDNIGSQYLLNWCVQIAKGMNYLEDR  786

         ************************************************************

S: 121   rlvhrdlaarnvlvkspnhvkitdfGlaklleadekelkaeggkvpikwlalesilkrky  180

         rlvhrdlaarnvlvk+p+hvkitdfGlakll a+eke++aeggkvpikw+alesil+r+y

Q: 787   RLVHRDLAARNVLVKTPQHVKITDFGLAKLLGAEEKEYHAEGGKVPIKWMALESILHRIY  846

         ************************************************************

S: 181   thqsdvwsyGvtvwelltfGakpydgipakeipdllekGerlaqppictidvymvlvkcw  240

         thqsdvwsyGvtvwel+tfG+kpydgipa+ei+++lekGerl+qppictidvym++vkcw

Q: 847   THQSDVWSYGVTVWELMTFGSKPYDGIPASEISSILEKGERLPQPPICTIDVYMIMVKCW  906

         ************************************************************

S: 241   midaesrpkfkelaeefs  258

         mida+srpkf+el+ efs

Q: 907   MIDADSRPKFRELIIEFS  924

         ****************96

Domain Sequence
(FASTA)

FKKIKVLGSG AFGTVYKGLW IPEGEKVKIP VAIKELREAT SPKANKEILD EAYVMASVDN 60

PHVCRLLGIC LTSTVQLITQ LMPFGCLLDY VREHKDNIGS QYLLNWCVQI AKGMNYLEDR 120

RLVHRDLAAR NVLVKTPQHV KITDFGLAKL LGAEEKEYHA EGGKVPIKWM ALESILHRIY 180

THQSDVWSYG VTVWELMTFG SKPYDGIPAS EISSILEKGE RLPQPPICTI DVYMIMVKCW 240

MIDADSRPKF RELIIEFS 258

Keyword

3D-structure; Alternative splicing; ATP-binding; Cell membrane; Complete proteome; Developmental protein; Direct protein sequencing; Disease mutation; Disulfide bond; Endoplasmic reticulum; Endosome; Glycoprotein; Golgi apparatus; Isopeptide bond; Kinase; Membrane; Methylation; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Receptor; Reference proteome; Repeat; Secreted; Signal; Transferase; Transmembrane; Transmembrane helix; Tumor suppressor; Tyrosine-protein kinase; Ubl conjugation.

Sequence Source

Ensembl

Orthology

Ortholog group

Anolis carolinensis"; ?>Bos taurus"; ?>Callithrix jacchus"; ?>Canis familiaris"; ?>Cavia porcellus"; ?>Equus caballus"; ?>Felis catus"; ?>Gasterosteus aculeatus"; ?>Gorilla gorilla"; ?>Ictidomys tridecemlineatus"; ?>Loxodonta africana"; ?>Macaca mulatta"; ?>Meleagris gallopavo"; ?>Monodelphis domestica"; ?>Mus musculus"; ?>Mustela putorius furo"; ?>Nomascus leucogenys"; ?>Oreochromis niloticus"; ?>Ornithorhynchus anatinus"; ?>Oryctolagus cuniculus"; ?>Oryzias latipes"; ?>Otolemur garnettii"; ?>Pan troglodytes"; ?>Pelodiscus sinensis"; ?>Pongo abelii"; ?>Rattus norvegicus"; ?>Sarcophilus harrisii"; ?>Taeniopygia guttata"; ?>Takifugu rubripes"; ?>Tetraodon nigroviridis"; ?>Xenopus tropicalis"; ?>Xiphophorus maculatus"; ?>

Gene Ontology

GO:0016323	; C:basolateral plasma membrane
GO:0030139	; C:endocytic vesicle
GO:0005789	; C:endoplasmic reticulum membrane
GO:0005768	; C:endosome
GO:0010008	; C:endosome membrane
GO:0005615	; C:extracellular space
GO:0000139	; C:Golgi membrane
GO:0016021	; C:integral to membrane
GO:0045121	; C:membrane raft
GO:0031965	; C:nuclear membrane
GO:0005634	; C:nucleus
GO:0048471	; C:perinuclear region of cytoplasm
GO:0070435	; C:Shc-EGFR complex
GO:0051015	; F:actin filament binding
GO:0005524	; F:ATP binding
GO:0003690	; F:double-stranded DNA binding
GO:0005006	; F:epidermal growth factor-activated receptor activity
GO:0004709	; F:MAP kinase kinase kinase activity
GO:0046982	; F:protein heterodimerization activity
GO:0004716	; F:receptor signaling protein tyrosine kinase activity
GO:0043006	; P:activation of phospholipase A2 activity by calcium-mediated signaling
GO:0007202	; P:activation of phospholipase C activity
GO:0007411	; P:axon guidance
GO:0008283	; P:cell proliferation
GO:0016337	; P:cell-cell adhesion
GO:0021795	; P:cerebral cortex cell migration
GO:0048546	; P:digestive tract morphogenesis
GO:0001892	; P:embryonic placenta development
GO:0001942	; P:hair follicle development
GO:0060571	; P:morphogenesis of an epithelial fold
GO:0043066	; P:negative regulation of apoptotic process
GO:0042059	; P:negative regulation of epidermal growth factor receptor signaling pathway
GO:0042177	; P:negative regulation of protein catabolic process
GO:0001503	; P:ossification
GO:0035413	; P:positive regulation of catenin import into nucleus
GO:0030335	; P:positive regulation of cell migration
GO:0031659	; P:positive regulation of cyclin-dependent protein kinase activity involved in G1/S
GO:0045739	; P:positive regulation of DNA repair
GO:0045740	; P:positive regulation of DNA replication
GO:0050679	; P:positive regulation of epithelial cell proliferation
GO:0048146	; P:positive regulation of fibroblast proliferation
GO:0043406	; P:positive regulation of MAP kinase activity
GO:0045429	; P:positive regulation of nitric oxide biosynthetic process
GO:0051897	; P:positive regulation of protein kinase B signaling cascade
GO:0046777	; P:protein autophosphorylation
GO:0051205	; P:protein insertion into membrane
GO:0050999	; P:regulation of nitric-oxide synthase activity
GO:0050730	; P:regulation of peptidyl-tyrosine phosphorylation
GO:0006950	; P:response to stress
GO:0070141	; P:response to UV-A
GO:0007435	; P:salivary gland morphogenesis

KEGG

hsa:1956

;

InterPros

IPR000494	; EGF_rcpt_L.
IPR006211	; Furin-like_Cys-rich_dom.
IPR006212	; Furin_repeat.
IPR009030	; Growth_fac_rcpt.
IPR011009	; Kinase-like_dom.
IPR000719	; Prot_kinase_cat_dom.
IPR017441	; Protein_kinase_ATP_BS.
IPR001245	; Ser-Thr/Tyr_kinase_cat_dom.
IPR008266	; Tyr_kinase_AS.
IPR020635	; Tyr_kinase_cat_dom.
IPR016245	; Tyr_kinase_EGF/ERB/XmrK_rcpt.

Pfam

PF00757	; Furin-like; 1.
PF07714	; Pkinase_Tyr; 1.
PF01030	; Recep_L_domain; 2.

SMARTs

SM00261	; FU; 3.
SM00219	; TyrKc; 1.

Prosites

PS00107	; PROTEIN_KINASE_ATP; 1.
PS50011	; PROTEIN_KINASE_DOM; 1.
PS00109	; PROTEIN_KINASE_TYR; 1.

Prints

PR00109

; TYRKINASE.

Created Date

20-Feb-2013