Supplementary Figure S1 - Plos

Supplementary Figure S1 D46N HOMO SAPIENS EGFR HOMO SAPIENS HER2 (ERBB2) HOMO SAPIENS HER3 (ERBB3) HOMO SAPIENS ERBB4 MUS MUSCULUS RATTUS NORVEGICUS SUS SCROFA DANIO RERIO DROSOPHILA MELANOGASTER XIPHOPHORUS (XMRK)

R324L E330K

G63R

KVCQGTSNKLTQLGTFEDHFLSLQRMFNNCEVVLGN-LEITYVQ-RNYDL QVCTGTDMKLRLPASPETHLDMLRHLYQGCQVVQGN-LELTYLP-TNASL AVCPGTLNGLSVTGDAENQYQTLYKLYERCEVVMGN-LEIVLTG-HNADL SVCAGTENKLSSLSDLEQQYRALRKYYENCEVVMGN-LEITSIE-HNRDL KVCQGTSNRLTQLGTFEDHFLSLQRMYNNCEVVLGN-LEITYVQ-RNYDL KVCQGTSNRLTQLGTFEDHFLSLQRMFNNCEVVLGN-LEITYVQ-RNYDL KVCQGTSNKLTQLGTFEDHFLSLQRMFNNCEVVLGN-LEITYMQ-NSYNL KVCQGANNKLTLLGTVEDHYQVLLRMYRNCTVVLEN-LEITHIT-EKYDL KVCIGTKSRLSVPSNKEHHYRNLRDRYTNCTYVDGN-LELTWLPNENLDL KVCQGTSNQMTML---DNHYLKMKKMYSGCNVVLENTLEITYTQ-ENQDL ** *: : : : : : * * * **:. . .*

76 71 74 74 76 76 76 73 99 73

HOMO SAPIENS EGFR HOMO SAPIENS HER2 (ERBB2) HOMO SAPIENS HER3 (ERBB3) HOMO SAPIENS ERBB4 MUS MUSCULUS RATTUS NORVEGICUS SUS SCROFA DANIO RERIO DROSOPHILA MELANOGASTER XIPHOPHORUS (XMRK)

YEME-EDGVRKCKKCEGPCRKVCNGIGIGEFKDSLSINATNIKHFKNCTS QEVTAEDGTQRCEKCSKPCARVCYGLGMEHLREVRAVTSANIQEFAGCKK MEVD-KNGLKMCEPCGGLCPKACEGTGSGSRF--QTVDSSNIDGFVNCTK MEVE-ENGIKMCKPCTDICPKACDGIGTGSLMSAQTVDSSNIDKFINCTK YEVE-EDGIRKCKKCDGPCRKVCNGIGIGEFKDTLSINATNIKHFKYCTA YEVE-EDGVSKCKKCDGPCRKVCNGIGIGEFKDTLSINATNIKHFKYCTA YEVE-EDGVRKCKKCDGPCGKVCNGIGIGEFKDTLSINATNIKHFRNCTS YEVD-EGGVRKCKRCEGLCPKVCNGLGMGPLANVLSINATNIDSFENCTK MDKG-----GECVPCNGPCPKTCPGVT--------VLHAGNIDSFRNCTV LEVD-ENGKRSCKPCDGVCPKVCDGIGIGSLSNTIAVNSTNIGSFSNCTK : * * * :.* * : : ** * *.

P596L

R108K HOMO SAPIENS EGFR HOMO SAPIENS HER2 (ERBB2) HOMO SAPIENS HER3 (ERBB3) HOMO SAPIENS ERBB4 MUS MUSCULUS RATTUS NORVEGICUS SUS SCROFA DANIO RERIO DROSOPHILA MELANOGASTER XIPHOPHORUS (XMRK)

SFLKTIQEVAGYVLIALNTVERIPLENLQIIRGNMYYENSYALAVLSNYD SFLQDIQEVQGYVLIAHNQVRQVPLQRLRIVRGTQLFEDNYALAVLDNGD SFLQWIREVTGYVLVAMNEFSTLPLPNLRVVRGTQVYDGKFAIFVMLNYN SFLRSVREVTGYVLVALNQFRYLPLENLRIIRGTKLYEDRYALAIFLNYR SFLKTIQEVAGYVLIALNTVERIPLENLQIIRGNALYENTYALAILSNYG SFLKTIQEVAGYVLIALNTVERIPLENLQIIRGNALYENTYALAVLSNYG SFLKTIQEVAGYVLIALNTVEKIPLENLQIIRGNVLYENTHALAVLSNYG SFLKSIQEVGGYVLIAVNTVSKIPLENLRIIRGHSLYEDKFALAVLVNFN SFLDNIREVTGYILISHVDVKKVVFPKLQIIRGRTLFSLSVEEEKYALFV SFLQSIQEVGGYVLIAMNEVSTIPLVNLRLIRGQNLYEGNFTLLVMSNYQ *** ::** **:*:: . : : .*:::** :.


QQCSG-RCRGKSPSDCCHNQCAAGCTGPRESDCLVCRKFRDEATCKDTCP GGCA--RCKGPLPTDCCHEQCAAGCTGPKHSDCLACLHFNHSGICELHCP PQCNG-HCFGPNPNQCCHDECAGGCSGPQDTDCFACRHFNDSGACVPRCP EQCDG-RCYGPYVSDCCHRECAGGCSGPKDTDCFACMNFNDSGACVTQCP QQCSH-RCRGRSPSDCCHNQCAAGCTGPRESDCLVCQKFQDEATCKDTCP QQCSR-RCRGRSPSDCCHNQCAAGCTGPRESDCLVCHRFRDEATCKDTCP QQCSG-RCRGRSPSDCCHNQCAAGCTGPRESDCLVCRRFRDEATCKDTCP EQCSG-RCKGPRPIDCCNEHCAAGCTGPRPTDCLACKDFQDEGTCKDACP PQCAGGRCYGPKPRECCHLFCAGGCTGPTQKDCIACKNFFDEGVCKEECP EQCNR-RCRGPKPIDCCNEHCAGGCTGPRATDCLACRDFNDDGTCKDTCP * :* * :**: **.**:** .**:.* * ... * **

126 121 124 124 126 126 126 123 149 123


T263P

PLMLYNPTTYQMDVNPEGKYSFGATCVKKCPRNYVVTDHGSCVRACGADS ALVTYNTDTFESMPNPEGRYTFGASCVTACPYNYLSTDVGSCTLVCPLHN QPLVYNKLTFQLEPNPHTKYQYGGVCVASCPHNFVVDQT-SCVRACPPDK QTFVYNPTTFQLEHNFNAKYTYGAFCVKKCPHNFVVDSS-SCVRACPSSK PLMLYNPTTYQMDVNPEGKYSFGATCVKKCPRNYVVTDHGSCVRACGPDY PLMLYNPTTYQMDVNPEGKYSFGATCVKKCPRNYVVTDHGSCVRACGPDY PLMLYNPTTYQMDVNPLGKYSFGATCVKKCPRNYVVTDHGSCVRACSSDS RLMLYDPNTHQLAPNPYGKYSFGATCIKTCPHNYVVTDHGACVRTCSPGT PMRKYNPTTYVLETNPEGKYAYGATCVKECPG-HLLRDNGACVRSCPQDK PPKIYDIVSHQVVDNPNIKYTFGAACVKECPSNYVVTEG-ACVRSCSAGM *: :. * :* :*. *: ** .: . :*. *

CIQCHPECLPQAM-NITCTGRGPDNCIQCAHYIDGPHCVKTCP------CLPCHPECQPQNG-SVTCFGPEADQCVACAHYKDPPFCVARCP------CFSCHPECQPMEG-TATCNGSGSDTCAQCAHFRDGPHCVSSCP------CVECDPQCEKMEDGLLTCHGPGPDNCTKCSHFKDGPNCVEKCP------CIQCHPECLPQAM-NITCTGRGPDNCIQCAHYIDGPHCVKTCP------CIQCHPECLPQTM-NITCTGRGPDNCIKCAHYVDGPHCVKTCP------CVQCHPECLPQAK-NVTCMGRGPDSCVRCAHYIDGPHCVKTCP------CMECDPECLLMNE-TQTCNGPGPDKCTVCANYKDGPHCVHRCP------CKICHPECR-------TCNGAGADHCQECVHVRDGQHCVSECPKNKYNDR CVQCHQECLVQTD-SLTCYGPGPANCSKCAHFQDGPQCIPRCP------* *. :* ** * . * * : * *: **

596 601 590 594 596 596 596 594 613 591

G598V 265 269 260 263 265 265 265 263 287 268


----------AGVMGENNTL-V-------------------------------------SGVKPDLSYMPI-------------------------------------HGVLGAKGPI---------------------------------------DGLQGANSFI---------------------------------------AGIMGENNTL-V-------------------------------------SGIMGENNTL-V-------------------------------------AGIAGENSTL-I-------------------------------------QGVPGEKDTL-I---------------------------GVCRECHATCDGCTGPKDTIGIGACTTCNLAIINNDATVKRCLLKDDKCP ----------HGMLGDGDTL-I---------------------------* . :

607 613 600 604 607 607 607 605 663 602

L861Q

A289D/T/V HOMO SAPIENS EGFR HOMO SAPIENS HER2 (ERBB2) HOMO SAPIENS HER3 (ERBB3) HOMO SAPIENS ERBB4 MUS MUSCULUS RATTUS NORVEGICUS SUS SCROFA DANIO RERIO DROSOPHILA MELANOGASTER XIPHOPHORUS (XMRK)

364 369 356 361 364 364 364 362 373 366

315 319 309 312 315 315 315 313 336 317


RDLAARNVLVKTPQHVKITDFGLAKLLGAEEKEYHAEGGKVPIKWMALES RDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGKVPIKWMALES RNLAARNVLLKSPSQVQVADFGVADLLPPDDKQLLYSEAKTPIKWMALES RDLAARNVLVKSPNHVKITDFGLARLLEGDEKEYNADGGKMPIKWMALEC RDLAARNVLVKTPQHVKITDFGLAKLLGAEEKEYHAEGGKVPIKWMALES RDLAARNVLVKTPQHVKITDFGLAKLLGAEEKEYHAEGGKVPIKWMALES RDLAARNVLVKTPQHVKITDFGLAKLLGAEEKEYHAEGGKVPIKWLALES RDLAARNVLVKTPQHVKITDFGLAKLLNADEKEYHADGGKVPIKWMALES RDLAARNVLVQTPSLVKITDFGLAKLLSSDSNEYKAAGGKMPIKWLALEC RDLAARNVLLKNPNHVKITDFGLSKLLTADEKEYQADGGKVPIKWMALES *:*******::.*. *:::***:: ** :..: .* ****:***.

885 893 882 891 887 886 885 884 1062 880