classification and characterization of natural protein inhibitors of protein kinases
DESCRIPTION
CLASSIFICATION AND CHARACTERIZATION OF NATURAL PROTEIN INHIBITORS OF PROTEIN KINASES AGATA MEGLICZ 1 , JACEK LELUK 1 , BOGDAN LESYNG 1,2 1 Interdisciplinary Centre for Mathematical and Computational Modelling (ICM), Warsaw University, Poland - PowerPoint PPT PresentationTRANSCRIPT
Jacek Leluk, Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw University
CLASSIFICATION AND CHARACTERIZATION
OF NATURAL PROTEIN INHIBITORS OF PROTEIN KINASES
AGATA MEGLICZ1, JACEK LELUK1, BOGDAN LESYNG1,2
1Interdisciplinary Centre for Mathematical and Computational Modelling (ICM), Warsaw University, Poland
2Department of Biophysics, Faculty of Physics, Warsaw University, Poland
Jacek Leluk, Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw University
Kinase project at ICM
Complex comparative studies at the primary structure level
Construction of molecular phylogenetic trees
Studies on sequence/structure/function relationship
Studies on the mechanisms of correlated mutations and variability
Genetic principles of differentiation within the kinase and kinase inhibitor families
Jacek Leluk, Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw University
Kinase protein inhibitors – current knowledge status
Although various protein kinase families are relatively well described, there is much less known about natural protein
inhibitors that control their activities.
Protein kinase inhibitors are not sufficiently well classified into homologous families.
There is not much known about their mechanisms of inhibition, and especially about structure-function relationships.
The mechanisms of their specific recognition processes is still unclear in many cases.
This limits the approaches aiming to select inhibitors of desired structural features and specificity.
Jacek Leluk, Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw University
The comparative study of primary structures of natural protein kinase inhibitors includes:
- a thorough classification of this group of proteins
- selecting the homologous families
- describing of each selected family with respect to their mutational variability, structural properties and select regions that are important for their specificity.
Our study started by selecting homologous inhibitor sequences.
Multiple alignment was carried out and consensus sequences were constructed with the aid of the programs GEISHA (written by Adam Górecki) and Consensus Constructor (both elaborated
at ICM).
Jacek Leluk, Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw University
Q90641------------MTDVESTYADFIASGRTGRRNALHDILVSSPGGNSSELA--L-KL-S-ELDINKAEGEGDAQ-RNPSEQTGEAQGEAAKQES----------- NP_032888.1-------MTDVETTYADFIASGRTGRRNAIHDILVSSASGNSNELA--L-KL--AGLDINKTEGEDDGQ-RSSTEQSGEAQGEAAKSES----------- NP_006814.1-------MTDVETTYADFIASGRTGRRNAIHDILVSSASGNSNELA--L-KL--AGLDINKTEGEEDAQ-RSSTEQSGEAQGEAAKSES----------- AAA72716.1--------GTDVETTYADFIASGRTGRRNAIHDILVSSASGNSNELA--L-KL--AGLDINKTEGEEDAQ-RSSTEQSGEAQGEAAKSES----------- AAD30289.1--------MTDVESTYADFIASGRTGRRNALHDILVSSPGGNSSELA--L-KL-S-ELDINKA-------------------------------------- OKRBCI ------------TDVETTYADFIASGRTGRRNAIHDILVSSASGNSNELA--L-KL--AGLDINKTEGEEDAQ-RSSTEQSGEAQGEAAKSES----------- NP_036759.1-------MTDVESVISSFASSARAGRRNALPDIQSSLATGGSPDLA--L-KL--EALAV-K----EDAK-MKN-EEKD--QGQPKKPLDEDK-------- AAQ17070.1--------MMEVESSYSDFISCDRTGRRNAVPDIQGDSEAVSVRKLAGDMGELALEG-AEGQAEGGTPDKEASN--QP---QSSDGTTSS----------- AAL90456.1--------MTDVESVISSFASSARAGRRNALPDIQSSLATGGSPDLA--L-KL--EALAV-K----EDAK-MKN-EEKD--QGQP-KPLDEDK-------- NP_035236.1-------MMEVESSYSDFISCDRTGRRNAVPDIQGDSEAVSVRKLAGDMGELALEG-AEGQAEGSTPDKEASS--QP---ESSDANTSS----------- NP_008997.1-------MMEVESSYSDFISCDRTGRRNAVPDIQGDSEAVSVRKLAGDMGELALEG-AEGQVEGSAPDKEAGN--QP---QSSDGTTSS----------- AAQ04718.1--------MMEVESSYSDFISCDRTGRRNAVPDIQGDSEAVSVRKLA--G-DM--GELAL---EGA----------------------------------- NP_115860.1-------MTDVESGVANFASSARAGRRNALPDIQSSAATDGTSDLP--L-KL--EALSV-K----EDAKEKD--EKTT--QDQLEKPQNEEK-------- AAQ17071.1--------MMEVESSYSDFISCDRSGRRNAVPDIQGDSEAVSVRKLAGDMGELALEG-AEGQAEVGTSDKEASS--QP---ESSDGTTSS----------- AAH61162.1--------MTDVESVITSFASSARAGRRNALPDIQSSLATSGSSDLP--L-KL--EALAV-K----EDAK-TKN-EEKD--QGQPKTPLNEGKKKKKKKKK Q04758------------MTDVESVITSFASSARAGRRNALPDIQSSLATSGSSDLP--L-KL--EALAV-K----EDAK-TKN-EEKD--QGQPKTPLNEGK-------- NP_032889.2-------MTDVESVITSFASSARAGRRNALPDIQSSLATSGSSDLP--L-KL--EALAV-K----EDAK-TKN-EEKD--QGQPKTPLNEGK-------- O70139------------MMEVESSYSDFISCDRTGRRNAVPDIQGDSEAVSVRKLAGDMGELALEG-AEGQAEGSTPDKEASS--QP---ESS----------------- P04541------------MTDVETTYADFIASGRTGRRNAIHDILVSSASGNSNELA--L-KL--AGLDINKTEGEEDAQ-RSSTEQSGEAQGEAAKSES----------- P27776------------MTDVETTYADFIASGRTGRRNAIHDILVSSASGNSNELA--L-KL--AGLDINKTEGEDDGQ-RSSTEQSGEAQGE----------------- NP_861460.1-------MTDVESGVANFASSARAGRRNALPDIQSSAATDGTSDLP--L-KL--EALSV-K----EDAKEKD--EKT--TQDQLEKPQNEEK-------- NP_861459.1-------MTDVESGVANFASSARAGRRNALPDIQSSAATDGTSDLP--L-KL--EALSV-K----EDAKEKD--EKT--TQDQLEKPQNEEK-------- NP_862822.1-------MTDVETTYADFIASGRTGRRNAIHDILVSSASGNSNELA--L-KL--AGLDINKTEGEEDAQ-RSSTEQSGEAQGEAAKSES----------- NP_861521.1-------MMEVESSYSDFISCDRTGRRNAVPDIQGDSEAVSVRKLAGDMGELALEG-AEGQVEGSAPDKEAGN--QP---QSSDGTTSS----------- NP_861520.1-------MMEVESSYSDFISCDRTGRRNAVPDIQGDSEAVSVRKLAGDMGELALEG-AEGQVEGSAPDKEAGN--QP---QSSDGTTSS----------- NP_703199.1-------MMEVESSYSDFISCDRTGRRNAVPDIQGDSEAVSVRKLAGDMGELALEG-AEGQAEGSTPDKEASS--QP---ESSDANTSS----------- NP_446224.1-------MTDVETTYADFIASGRTGRRNAIHDILVSSASGNSNELA--L-KL--AGLDINKTEGEDDGQ-RSSTEQSGEAQGEAAKSES----------- AAH36011.1--------MTDVESGVANFASSARAGRRNALPDIQSSAATDGTSDLP--L-KL--EALSV-K----EDAKEKDE--KT--TQDQL---------------- AAH22265.1--------MTDVETTYADFIASGRTGRRNAIHDILVSSASGNSNELA--L-KL--AGLDINKTEGEEDAQ-RSSTEQSGEAQGEAAKSES----------- AAH48244.1--------MTDVETTYADFIASGRTGRRNAIHDILVSSASGNSNELA--L-KL--AGLDINKTEGEDDGQ-RSSTEQSGEAQGEAAKSES----------- Q9C010------------MTDVESGVANFASSARAGRRNALPDIQSSAATDGTSDLP--L-KL--EALSV-K----EDAKEKDE--KTTQDQL--EKPQNEEK-------- P27775------------MTDVESVISSFASSARAGRRNALPDIQSSLATGGSPDLA--L-KL--EALAV-K----EDAK-MKN-EEKD--QGQPKKPLDEDK-------- AAA40867.1--------MTDVETTYADFIASGRTGRRNAIHDILVSSASGNSNELA--L-KL--AGLDINKTEGEDDGQ-RSSTEQSGEAQGE----------------- Q9Y2B9------------MMEVESSYSDFISCDRTGRRNAVPDIQGDSEAVSVRKLAGDMGELALEG-AEGQVEGSAPDKEAGN--QP---QSS----------------- JC4128------------MTDVESTYADFIASGRTGRRNALHDILVSSPGGNSSELA--L-KL-S-ELDINKAEGEGDAQ-RNPSEQTGEAQGEAAKQES----------- B46707------------MTDVESVITSFASSARAGRRNALPDIQSSLATSGSSDLP--L-KL--EALAV-K----EDAK-TKN-EEKD--QGQPKTPLNEGK-------- A40962------------MTDVESVISSFASSARAGRRNALPDIQSSLATGGSPDLA--L-KL--EALAV-K----EDAK-MKN-EEKD--QGQPKKPLDEDK-------- A40536------------MTDVETTYADFIASGRTGRRNAIHDILVSSASGNSNELA--L-KL--AGLDINKTEGEDDGQ-RSSTEQSGEAQGE----------------- OKRBCI ------------TDVETTYADFIASGRTGRRNAIHDILVSSASGNSNELA--L-KL--AGLDINKTEGEEDAQ-RSSTEQSGEAQGEAAKSES----------- AAK00638.1--------MTDVESGVANFASSARAGRRNALPDIQSSAATDGTSDLP--L-KL--EALSV-K----EDAKEKDE--KTTQDQL------------------ AAD55445.1--------MMEVESSYSDFISCDRTGRRNAVPDIQGDSEAVSVRKLAGDMGELALEG-AEGQVEGSAPDKEAGN--QP---QSSDGTTSS----------- AAC09065.1--------MMEVESSYSDFISCDRTGRRNAVPDIQGDSEAVSVRKLAGDMGELALEG-AEGQAEGSTPDKEASS--QP---ESS----------------- AAB59678.1--------MTDVESVITSFASSARAGRRNALPDIQSSLATSGSSDLP--L-KL--EALAV-K----EDAK-TKN-EEKD--QGQPKTPLNEGK-------- AAA86697.1--------MTDVESTYADFIASGRTGRRNALHDILVSSPGGNSSELA--L-KL-S-ELDINKAEGEGDAQ-RNPSEQTGEAQGE-----------------
Multiple alignment of the „cAMP inhibitor family”
Jacek Leluk, Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw University
10 20 30 40 50 60 70 80 | | | | | | | | 1 O19002 -------------MSEPSRDAHQIPHG-SKACRRLFGPVDSEQLRRDCDALMAGCVQEARER-WNFDFVTETPLEGDFAW 2 AAH01935.1 -------------MSEPAGDVRQNPCG-SKACRRLFGPVDSEQLRRDCDALMAGCIQEARER-WNFDFVTETPLEGDFAW 3 NP_000380.1 -------------MSEPAGDVRQNPCG-SKACRRLFGPVDSEQLSRDCDALMAGCIQEARER-WNFDFVTETPLEGDFAW 4 AAG15411.1 -------------MSEPAGDVRQNPCG-SKACRRLFGPVDSEQLSRDCDALMAGCIQEARER-WNFDFVTETPLEGDFAW 5 NP_031695.1 -------------MSNP-GDVRPVPHR-SKVCRCLFGPVDSEQLRRDCDALMAGCLQEARER-WNFDFVTETPLEGNFVW 6 NP_542960.1 -------------MS-DPGDVRPVPHR-SKVCRRLFGPVDSEQLSRDCDALMASCLQEARER-WNFDFATETPLEGNYVW 7 AAC27627.1 ---------------------------------------------------------------WNLDLGTETPLEGDFVW 8 AAN63876.1 -----------------------MPCS-SKACRNLFGPVDHEQIQNDFEQLLRQQLEEA-QRRWNFNFETETPLEGHFKW 9 I51683 MAAFHIALQEEMIVASPAALPRLSLGTGRGACRNLFGPIDHDELRSELKRQLKEIQASDCQR-WNFDFESGTPLKGTFCW 19 CAA59284.1 MSNVRVSNGSPSLERMDA---RQAEHPKPSACRNLFGPVDHEELTRDLEKHCRDMEEAS-QRKWNFDFQNHKPLEGKYEW 11 AAF69497.1 MSNVRVSNGSPSLERMDA---RQAEHPKPSACRNLFGPVDHEELTRDLEKHCRDMEEAS-QRKWNFDFQNHKPLEGKYEW 12 NP_004055.1 MSNVRVSNGSPSLERMDA---RQAEHPKPSACRNLFGPVDHEELTRDLEKHCRDMEEAS-QRKWNFDFQNHKPLEGKYEW 13 AAC59775.1 MAAFHIALQEEMISAP-AVLPRLSAGTGRGACRNLFGPIDHDEMRSELKRQLKEIQASDCQR-WNFDFETGTPLKGIFCW 14 NP_034005.1 MSNVRVSNGSPSLERMDA---RQADHPKPSACRNLFGPVNHEELTRDLEKHCRDMEEAS-QRKWNFDFQNHKPLEGRYEW 15 Q60439 MSNVRVSNGSPSLERMDA---RQAEHPKPSACRNLFGPVNHEELTRDLEKHCRDMEEAS-QRKWNFDFQNHNPLEGRYQW 16 P46529 MSNVRVSNGSPSLERMDA---RQAEYPKPSACRNLFGPVNHEELTRDLEKHRRDMEEAS-QRKWNFDFQNHKPLEGKYEW 17 NP_113950.1 MSNVRVSNGSPSLERMDA---RQTEHPKPSACRNLFGPVNHEELTRDLEKHCRDMEEAS-QRKWNFDFQNHKPLEGRYEW 18 BAA19960.1 MSNVRVSNGSPSLERMDA---RQTEHPKPSACRNLFGPVNHEELTRDLEKHCRDMEEAS-QRKWNFDFQNHKPLEGRYEW 19 O19001 MSNVRVSNGSPSLERMDA---RQAEYPKPSACRNLFGPVNHEELTRDLEKHCRDMEEAS-QRKWNFDFQNHKPLEGKYEW 20 BAB39725.1 MSNVRVSNGSPSLERMDA---RQAEYPKPSACRNLFGPVNHEELTRDLEKHCRDMEEAS-QRKWNFDFQNHKPLEGKYEW 21 AAM22491.1 MSNVRISNGSPTLERMEA---RQSEYPKPSACRNLFGPVNHEELNRDLKKHRKEMEEAC-QRKWNFDFQNHKPLEGRYEW 22 BAA11015.1 ------------MERLVARGTFPVLVRT-SACRSLFGPVDHEELSRELQARLAELNAED-QNRWDYDFQQDMPLRGPGRL 23 NP_000067.1 MSDASLRSTS-TMERLVARGTFPVLVRT-SACRSLFGPVDHEELSRELQARLAELNAED-QNRWDYDFQQDMPLRGPGRL CONSENSUS MSNVRXSNGSPXLERMDA---RQXXXPKPSACRNLFGPVDHEELXRDLEKHXRXMEEAX-QRKWNFDFQNHXPLEGXYXW
Multiple alignment of the Cip inhibitor family
Jacek Leluk, Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw University
50 60 70 80 90 100 110 120 130 140 150 160 170 180 | | | | | | | | | | | | | | 1 NP_001791.1 EVRAGDRLSGAAARGDVQEVRRLLHRELV-HPDALNRFGKTALQVMMFGSTAIALELLKQGASPNVQDTSGTS-PVHDAARTGFLDTLKVLVEH--GADVNVPDGTGALPIHLAVQEGHTAVVSFLAAES--DLHRRDARGLTP 2 AAA85436.1 EVRAGDRLSGAAARGDVQEVRRLLHRELV-HPDALNRFGKTALQVMMFGSTAIALELLKQGASPNVQDTSGTS-PVHDAARTGFLDTLKVLVEH--GADVNVPDGTGALPIHLAVQEGHTAVVSFLAAES--DLHRRDARGLTP 3 A57378 EVRAG-TLSGAAARGDVQEVRRLLHRELV-HPDALNRFGKTALQVMMFGSTAIALELLKQGASPNVQDTSGTS-PVHDAARTGFLDTLKVLVEH--GADVNVPDGTGALPIHLAVQEGHTAVVSFLAAES--DLHRRDARGLTP 4 Q60773 EVCVGDRLSGARARGDVQEVRRLLHRELV-HPDALNRFGKTALQVMMFGSPAVALELLKQGASPNVQDASGTS-PVHDAARTGFLDTLKVLVEH--GADVNALDSTGSLPIHLAIREGHSSVVSFLAPES--DLHHRDASGLTP 5 NP_034008.1 EVCVGDRLSGARPRGDVQEVRRLLHRELV-HPDALNRFGKTALQVMMFGSPAVALELLKQGASPNVQDASGTS-PVHDAARTGFLDTLKVLVEH--GADVNALDSTGSLPIHLAIREGHSSVVSFLAPES--DLHHRDASGLTP 6 CAC12811.1 QMDAGKALAAAAAKGRTSEVQRILEECRV-PPDTRNEFGKTALQVMMLGNCKIASLLLEKGADPNVQDKHGIA-PVHDAARTGFLDTLQVLVEY--GASVNLPDQSGALPIHIAIREGHRDVVEFLAPRS--DLKHANKSGQTA 7 NP_571977.1 EPWGNE-LASAAARGDLEQLTSLLQNN-V-NVNAQNGFGRTALQVMKLGNPEIARRLLLRGANPNLKDRTGFA-VIHDAARAGFLDTVQALLEFQ--ADVNIEDNEGNLPLHLAAKEGHLPVVEFLMKHTACNVGHRNHKGDTA 8 AAL76343.1 EPWGNE-LASAAARGDLEQLTSLLQNN-V-NVNAQNGFGRTALQVMKLGNPEIARRLLLRGANPNLKDRTGFA-VIHDAARAGFLDTVQALLEFQ--ADVNIEDNEGNLPLHLAAKEGHLPVVEFLMKHTACNVGHRNHKGDTA 9 NP_031696.1 GGSSDAGLATAAARGQVETVRQLLEAGADPNAL--NRFGRRPIQVMMMGSAQVAELLLLHGAEPNCADPATLTRPVHDAAREGFLDTLVVLHRA--GARLDVCDAWGRLPVDLAEEQGHRDIARYLHAATG-D----------- 10 AAD00236.1 --------------------------------------------VMMMGNVHVAALLLNYGADSNCEDPTTFSRPVHDAAREGFLDTLVVLHGS--GARLDVRDAWGRLPLDLAQERGHQDIVRYLRSAGC-SLCSAGWSLCTA 11 AAD00231.1 --------------------------------------------VMMMGNVHIAALLLNYGADSNCEDPTTFSRPVHDAAREGFLDTLVVLHGS--GARLDVRDAWGRL-LDLAQERGHQDIVRYLRSAGC-SLCSAGWSLCTA 12 AAD00227.1 --------------------------------------------VMMMGNVHVAALLLNYGADSNCEDPTTFSRPVHDAAREGFLDTLVVLQGS--GARLDVRDAWGRLPLDLAQERGHQDIVRYLRSAGS-SLCSAGWSLCTA 13 AAD00229.1 --------------------------------------------VMMMGNVHVAALLLNYGADSNCEDPTTFSRPVHDAAREGFLDTLVVLQGS--GARLDVRDAWGRLPLDLAQERGHQDIVRYLRSAGW-SLCSAGWSLCTA 14 AAD00228.1 --------------------------------------------VMMMGNVHIAALLLNYGADSNCEDPTTFSRPVHDAAREGFLDTLVVLQGS--GARLDVRDAWGRLPLDLAQERGHQDIVRYLRSAGS-SLCSAGWSLCTA 15 AAD00230.1 --------------------------------------------VMMMGNVHVAALLLNYGADSNCEDPTTFSRPVHDAAREGFLDTLLVLHGS--GARLDVRDAWGRLPLDLAQERGHQDIVRYLRSAGW-SLCSAGWSLCTA 16 P51480 MESAADRLARA-AQGRVHDVRALLEAGVSPNAP--NSFGRTPIQVMMMGNVHVAALLLNYGADSNCEDPTTFSRPVHDAAREGFLDTLVVLHGS--GARLDVRDAWGRLPLDLAQERGHQDIVRYLRSAGC-SLCSAGWSLCTA 17 AAC08963.1 MESAADRLARAAAQGRVHDVRALLEAGVSPNAP--NSFGRTPIQVMMMGNVHVAALLLNYGADSNCEDPTTFSRPVHDAAREGFLDTLVVLHGS--GARLDVRDAWGRLPLDLAQERGHQDIVRYLRSAGC-SLCSAGWSLCTA 18 AAC08962.1 MESAADRLARAAAQGRVPDVRALLEAGVSPNAP--NSFGRTPIQVMMMGNVHIAALLLNYGADSNCEDPTTFSRPVHDAAREGFLDTLVVLHGS--GARLDVRDAWGRLPLDLAQERGHQDIVRYLRSAGC-SLCSAGWSLCTA 19 AAB39600.1 MESAADRLARAAAQGRVHDVRALLEAGVSPNAP--NSFGRTPIQVMMMGNVHVAALLLNYGADSNCEDPTTFSRPVHDAAREGFLDTLVVLHGS--GARLDVRDAWGRLPLDLAQERGHQDIVRYLRSAGC-SLCSAGWSLCTA 20 NP_113738.1 MESSADRLARAAALGREHEVRALLEAGASPNAP--NTFGRTPIQVMMMGNVKVAALLLSYGADSNCEDPTTLSRPVHDAAREGFLDTLVVLH--QAGARLDVRDAWGRLPLDLALERGHHDVVRYLR-----------YLLSSA 21 AAG44950.1 MEPSADGLARAAAQGREQEVRALLEAGVSPNAP--NCFGRTPIQVMMMGNTQVARLLLLYGAEPNCEDPATLSRPVHDAAREGFLETLAILH--QAGARLDVLDARGRLPVDLALERGHCDVVQYLRAAGN-TPQGSEPAGVTS 22 AAG59801.1 MEPSADGLARAAAQGREQEVRALLEAGVSPNAP--NCFGRTPIQVMMMGNTQVARLLLLYGAEPNCEDPATLSRPVHDAAREGFLETLAILH--QAGARLDVLDARGRLPVDLALERGHCDVVQYLRAAGN-TPQGSEPAGVTS 23 NP_031697.1 NELASA-----AARGDLEQLTSLLQNNVNVNAQ--NGFGRTALQVMKLGNPEIARRLLLRGANPNLKDGTGFA-VIHDAARAGFLDTVQALLEFQ--ADVNIEDNEGNLPLHLAAKEGHLPVVEFLMKHTACNVGHRNHKGDTA 24 NP_570825.1 GGGSDAGLATAAARGQVETVRQLLEAGADPNAV--NRFGRRPIQVMMMGSAQVAELLLLHGAEPNCADPATLTRPVHDAAREGFLDTLMVLHKA--GARLDVCDAWGRLPVDLAEEQGHRDIARYLHAATG-D----------- 25 CAC67498.1 GGGSDAGLATAAARGQVETVRQLLEAGVDPNAV--NRFGRRPIQVMMMGSTQVAELLLLHGAEPNCADPNTLTRPVHDAAREGFLDTLVVLHRA--GARLDVRDTWGRLPVDLAEEMGHHDVAVYLHAATG-D----------- 26 NP_004927.2 GGGSDEGLASAAARGLVEKVRQLLEAGADPNGV--NRFGRRAIQVMMMGSARVAELLLLHGAEPNCADPATLTRPVHDAAREGFLDTLVVLHRA--GARLDVRDAWGRLPVDLAEERGHRDVAGYLRTATG-D----------- 27 AAA50282.1 GGGSDEGLAT-PARGLVEKVRHSWEAGADPNGV--NRFGRRAIQVMMMGSARVAELLLLHGAEPNCADPATLTRPVHDAAREGFLDTLVVLHRA--GARLDVRDAWGRLPVDLAEERGHRDVAGYLRTATG-D----------- 28 CAC87045.1 GGGGDAGLANAAARGQVETVRQLLEAGADPNGL--NHFGRRPIQVMMMGSARVAELLLLHGADPNCADPATLTRPVHDAAREGFLDTLVALRRA--GARLDVQDAWGRLPVDLAEERGHRDVARFLRAAAG-D----------- 29 AAC97110.1 -------------------------AGADPNGV--NGFGRRPIQVMMMGSVHVAELLLLHGADPNRADPDTLTRPVHDAAREGFL----------------------------------------------------------- 30 CAC87046.1 MEPSADWLASAAARGREGEVRALLEAGALANAP--NRYGRTPIQVMMMGSTRVAELLLLHGADPNCEDPATLTRPVHDAAREGFLDTLVVLHRA--GARLDVRDAWGRLPVDLAEERGHRDVAGYLRANAG-RTEGGSHARSNS 31 CAB65454.1 --------------------------------------------VMMMGSTRVAELLLLHGADPNCEDPATLTRPVHDAAREGFLDTLVVLHRA--GARLDVRDAWGRLPVDLAEERGHRDVAGYLRANAG-RTEGGSHARSNS 32 BAA33541.1 --------------------------------------------VMMMGSARVAELLLLHGADPNCADPATLTRPVHDAAREGFLDTLVVLHRA--GARLDVRDAWGRLPVDLAEERGHRDVARYLRAAAG-D----------- 33 BAA33540.1 --------------------------------------------VMMMGSARVAELLLLHGADPNCADPATLTRPVHDAAREGFLDTLVVLHRA--GARLDVRDAWGRLPVDLAEERGHRDIVRYLRARTG-GTGSGSHTGTDG 34 CAB65455.1 --------------------------------------------VMMMGSARVAELLLLHGADPNCADPATLTRPVHDAAREGFLDTLVALRRA--GARLDVQDAWGRLPVDLAEERGHRDVARFLRAAAG-D----------- 35 P42771 MEPSADWLATAAARGRVEEVRALLEAGALPNAP--NSYGRRPIQVMMMGSARVAELLLLHGAEPNCADPATLTRPVHDAAREGFLDTLVVLHRA--GARLDVRDAWGRLPVDLAEELGHRDVARYLRAAAG-GTRGSNHARIDA 36 NP_000068.1 MEPSADWLATAAARGRVEEVRALLEAGALPNAP--NSYGRRPIQVMMMGSARVAELLLLHGAEPNCADPATLTRPVHDAAREGFLDTLVVLHRA--GARLDVRDAWGRLPVDLAEELGHRDVARYLRAAAG-GTRGSNHARIDA 37 AAB60645.1 MEPSADWLATAAARGRVEEVRALLEAGALPNAP--NSYGRRPIQVMMMGSARVAELLLLHGAEPNCADPATLTRPVHDAAREGFLDTLVVLHRA--GARLDVRDAWGRLPVDLAEELGHRDVARYLRAAAG-GTRGSNHARIDA 38 NP_478103.1 ---------------------------------------------MMMGSARVAELLLLHGAEPNCADPATLTRPVHDAAREGFLDTLVVLHRA--GARLDVRDAWGRLPVDLAEELGHRDVARYLRAAAG-GTRGSNHARIDA 39 AAD14050.1 --------------------------------------------VMMMGSARVAELLLLHGAEPNCADPATLTRPVHDAAREGFLDTLVVLHRA--GARLDVRDAWGRLPVDLAEELGHRDVARYLRAAAG-GTRGSNHARIDA 40 2002364A MEPSADWLATAAARGRVEEVRALLEAVALPNAP--NSYGRRPIQVMMMGSARVAELLLLHGAEPNCADPATLTRPVHDAAREGFLDTLVVLHRA--GARLDVRDAWGRLPVDLAEELGHRDVARYLRAAAG-GTRGSNHARIDA 41 AAB32713.1 MEPSADWLATAAARGRVEEVRALLEAVALPNAP--NSYGRRPIQVMMMGSARVAELLLLHGAEPNCADPATLTRPVHDAAREGFLDTLVVLHRA--GARLDVRDAWGRLPVDLAEELGHRDVARYLRAAAG-GTRGSNHARIDA 42 AAG01087.1 --------------------------------------------VMMMGSARVAELLLLHGAEPNCADPVTLTRPVHDAAREGFLDTLVVLHRA--GARLDVRDAWGRLPVDLAEELGHRDVARYLA----------------- 43 AAD00232.1 --------------------------------------------VMMMGSAQVAELLLLHGAEPNCADPATLTRPVHDAAREGFLDTLVVLHRA--GARLDVCDAWGRLPVDLAEEQGHRDIARYLHAATG-D----------- 44 AAB94534.1 --------------------------------------------VIMMGSAQVAELLLLHGAEPNCADPATLTRPVHDAAREGFLDTLVVLHRA--GARLDVCDAWGRLPVDLAEEQGHRDIARYLHAASG-D----------- 45 O77617 ESFSGEKLTEAAARGRTEVVTELLELGTNPNAV--NRFGRSAIQVMMMGNVRLAAILLQYGAEPNTPDPTTLTLPVHDAAREGFLDTLMLLHRA--GARLDVRDSWGRLPVDLAEEQGHHLVVAYLREVVR-DA---------- 46 NP_478104.1 MEPSADWLATAAARGRVEEVRALLEAGALPNAP--NSYGRRPIQVGRR-------------SAAGAGDGGRLWRTKFAGELE-------------SGSASILRKK-GRLPGEFSEG-----VCNHRPPPG--DALGAWETKEEE CONSENSUS --XXXXXLXXAXAXGX-XXXXXLLX--XXXXXX--NXXGXXXXQVMMMGX-XVA-LLLXXGAXPNCXDPXTXXRPVHDAAREGFLDTLXVLXXX--GARLDVXDAWGRLPXDLAXEXGHXDVX-YLRXAXX-XXXXXXXXX---
Multiple alignment of the Ink4 inhibitor family
Jacek Leluk, Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw University
Multiple alignment of the KCIP-1 inhibitor family (part 1/3)
10 20 30 40 50 60 70 80 90 | | | | | | | | | 1. P29358 TM-DKSE-LVQKAKLAEQAERYDDMAAAMKAVTEQGHELSNEERNLLSVAYKNVVGARRSSWRVISSIEQKTE--RNEKKQQMGKEYREK 2. P29359 TM-DKSE-LVQKAKLAEQAERYDDMAAAMKAVTEQGHELSNEERNLLSVAYKNVVGARRSSWRVISSIEQKTE--RNEKKQQMGKEYREK 3. Q9CQV8 TM-DKSE-LVQKAKLAEQAERYDDMAAAMKAVTEQGHELSNEERNLLSVAYKNVVGARRSSWRVISSIEQKTE--RNEKKQQMGKEYREK 4. P35213 TM-DKSE-LVQKAKLAEQAERYDDMAAAMKAVTEQGHELSNEERNLLSVAYKNVVGARRSSWRVISSIEQKTE--RNEKKQQMGKEYREK 5. S23179 -M-DKSE-LVQKAKLAEQAERYDDMAAAMKAVTEQGHELSNEERNLLSVAYKNVVGARRSSWRVISSIEQKTE--RNEKKQQMGKEYREK 6. NP_003395 -M-DKNE-LVQKAKLAEQAERYDDMAACMKSVTEQGAELSNEERNLLSVAYKNVVGARRSSWRVVSSIEQKTE--GAEKKQQMAREYREK 7. BAA11751 -M-DKNE-LVQKAKLAEQAERYDDMAACMKSVTEQGAELSNEERNLLSVAYKNVVGARRSSWRVVSSIEQKTE--GAEKKQQVAREYREK 8. P29361 -M-DKNE-LVQKAKLAEQAERYDDMAACMKSVTEQGAELSNEERNLLSVAYKNVVGARRSSWRVVSSIEQKTE--GAEKKQQMAREYREK 9. BAA13421 -M-DKNE-LVQKAKLAEQAERYDDMAACMKSVTEQGAELSNEERNLLSVAYKNVVGARRSSWRVVSSIEQKTE--GAEKKQQMAREYREK 10. NP_003397 -M-DKNE-LVQKAKLAEQAERYDDMAACMKSVTEQGAELSNEERNLLSVAYKNVVGARRSSWRVVSSIEQKTE--GAEKKQQMAREYREK 11. S65013 -M-DKNE-LVQKAKLAEQAERYDDMAAAMKSVTEQGAELSNEERNLLSVAYKNVVGARRSSWRVVSSIEQKTE--GAEKKQQMAREYREK 12. P29309 ------------AKLSEQAERYDDMAASMKAVTELGAELSNEERNLLSVAYKNVVGARRSSWRVISSIEQKTE--GNDKRQQMAREYREK 13. AAC41252 M-DKNE-LVQKAKLAEQAERYDDMAACMKRVTEEGGELSNEERNLLSVAYKNVVGARRSSWRVVSSIEQKTE--GAEKKQEMSREYREK 14. P31946 -MVD-REQLVQKARLAEQAERYDDMAAAMKNVTELNEPLSNEERNLLSVAYKNVVGARRSSWRVISSIEQKTSADGNEKKIEMVRAYREK 15. P42655 -MDD-REDLVYQAKLAEQAERYDEMVESMKKVAGMDVELTVEERNLLSVAYKNVIGARRASWRIISSIEQKEENKGGEDKLKMIREYRQM 16. P11576 ---GDREQLLQRARLAEQAERYDDMASAMKAVTELNEPLSNEDRNLLSVAYKNVVGARRSSWRVISSIEQKTMADGNEKKLEKVKAYREK 17. P35214 ---VDREQLVQKARLAEQAERYDDMAAAMKNVTELNEPLSNEERNLLSVAYKNVVGARRSSWRVISSIEQKTSADGNEKKIEMVRAYREK 18. P29312 -M-DKNE-LVQKAKLAEQAERYDDMAACMKSVTEQGAELSNEERNLLSVAYKNVVGARRSSWRVVSSIEQKTE--GAEKKQQMAREYREK 19. P35215 -M-DKNE-LVQKAKLAEQAERYDDMAACMKSVTEQGAELSNEERNLLSVAYKNVVGARRSSWRVVSSIEQKTE--GAEKKQQMAREYREK 20. JC5384 -M-DKNE-LVQKAKLAEQAERYDDMAACMKSVTEQGAELSNEERNLLSVAYKNVVGARRSSWRVVSSIEQKTE--GAEKKQQMAREYREK CONSENSUS -M-DKXE-LVQKAKLAEQAERYDDMAAXMK-VTEQG-ELSNEERNLLSVAYKNVVGARRSSWRVXSSIEQKTE--X-EKKXXMXREYREK
Jacek Leluk, Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw University
Multiple alignment of the KCIP-1 inhibitor family (part 2/3)
10O 11O 12O 13O 14O 15O 160 17O 1 | | | | | | | | | 1. P29358 IEAELQDICNDVLELLDKYLIPNATQP--ESKVFYLKMKGDYFRYLSEVASGDNKQTTVSNSQQAYQEAFEISK-KEMQPTHPIRLGLAL 2. P29359 IEAELQDICNDVLQLLDKYLIPNATQP--ESKVFYLKMKGDYFRYLSEVASGDNKQTTVSNSQQAYQEAFEISK-KEMQPTHPIRLGLAL 3. Q9CQV8 IEAELQDICNDVLELLDKYLILNATQA--ESKVFYLKMKGDYFRYLSEVASGENKQTTVSNSQQAYQEAFEISK-KEMQPTHPIRLGLAL 4. P35213 IEAELQDICSDVLELLDKYLILNATHA--ESKVFYLKMKGDYFRYLSEVASGDNKQTTVSNSQQAYQEAFEISK-KEMQPTHPIRLGLAL 5. S23179 IEAELQDICNDVLQLLDKYLIPNATQP--ESKVFYLKMKGDYFRYLSEVASGDNKQTTVSNSQQAYQEAFEISK-KEMQPTHPIRLGLAL 6. NP_003395 IETELRDICNDVLSLLEKFLIPNASQP--ESKVFYLKMKGDYYRYLAEVAAGDDKKG-VDQSQQAYQEAFEISKIKEMQPTHPIRLGLAL 7. BAA11751 IETELRDICNDVLSLLEKFLIPNASQP--ESKVFYLKMKGDYYRYLAEVAAGDDKKGIVDQSQQAYQEAFEISK-KEMQPTHPIRLGLAL 8. P29361 IETELRDICNDVLSLLEKFLIPNRSQP--ESKVFYLKMKGDYYRYLAEVAAGDDKKGIVDQSQQAYQEAFEISK-KEMQPTHPIRLGLAL 9. BAA13421 IETELRDICNDVLSLLEKFLIPNASQP--ESKVFYLKMKGDYYRYLAEVAAGDDKKGIVDQSQQAYQEAFEISK-KEMQPTHPIRLGLAL 10. NP_003397 IETELRDICNDVLSLLEKFLIPNASQA--ESKVFYLKMKGDYYRYLAEVAAGDDKKGIVDQSQQAYQEAFEISK-KEMQPTHPIRLGLAL 11. S65013 IETELRDICNDVLSLLEKFLIPNASQA--ESKVFYLKMKGDYYRYLAEVAAGDDKKGIVDQSQQAYQEAFEISK-KEMQPTHPIRLGLAL 12. P29309 VETELQDICKDVLDLLDRFLVPNATPP--ESKVFYLKMKGDYYRYLSEVASGDSKQETVASSQQAYQEAFEISK-SEMQPTHPIRLGLAL 13. AAC41252 IEAELREICNDVLNLLDKFLIANATQP--ESKVFYLKMKGDYYRYLAEVAAGNAKTEIVGQSQKAYQDAFDISK-TEMQPTHPIRLGLAL 14. P31946 IEKELEAVCQDVLSLLDNYLIKNCSETQIESKVFYLKMKGDYYRYLAEVATGEKRATVVESSEKAYSEAHEISK-EHMQPTHPIRLGLAL 15. P42655 VETELKLICCDILDVLDKHLIPAANTG--ESKVFYYKMKGDYHRYLAEFATGNDRKEAAENSLVAYKAASDIAM-TELPPTHPIRLGLAL 16. P11576 IEKELETVCNDVLALLDKFLIKNCNDFQYESKVFYLKMKGDYYRYLAEVASGEKKNSVVEASEAAYKEAFEISK-EHMQPTHPIRLGLAL 17. P35214 IEKELEAVCQDVLSLLDNYLIKNCSETQYESKVFYLKMKGDYYRYLAEVATGEKRATVVESSEKAYSEAHEISK-EHMQPTHPIRLGLAL 18. P29312 IETELRDICNDVLSLLEKFLIPNASQA—-ESKVFYLKMKGDYYRYLAEVAAGDDKKGIVDQSQQAYQEAFEISK-KEMQPTHPIRLGLAL 19. P35215 IETELRDICNDVLSLLEKFLIPNASQP—-ESKVFYLKMKGDYYRYLAEVAAGDDKKGIVDQSQQAYQEAFEISK-KEMQPTHPIRLGLAL 20. JC5384 IETELRDICNDVLSLLEKFLIPNRSQP—-ESKVFYLKMKGDYYRYLAEVAAGDDKKGIVDQSQQAYQEAFEISK-KEMQPTHPIRLGLAL CONSENSUS IEXELXDICNDVLXLLXK-LIPNAXQ---ESKVFYLKMKGDYYRYLAEVAXGXXKXXXVX-SQQAYQEAFEISK-KEMQPTHPIRLGLAL
Jacek Leluk, Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw University
Multiple alignment of the KCIP-1 inhibitor family (part 3/3)
190 200 210 220 230 240 250 | | | | | | | | 1. P29358 NFSVFYYEILNSPEKACSLAKTAFDEAIAELDTLNEESYKDSTLIMQLLRDNLTLWTSENQGDEGDAGEG-EN------- 2. P29359 NFSVFYYEILNSPEKACSLAKTAFDEAIAELDTLNEESYKDSTLIMQLLRDNLTLWTSENQGDEGDAGEG-EN------- 3. Q9CQV8 NFSVFYYEILNSPEKACSLAKTAFDEAIAELDTLNEESYKDSTLIMQLLRDNLTLWTSENQGDEGDAGEG-EN------- 4. P35213 NFSVFYYEILNSPEKACSLAKTAFDEAIAELDTLNEESYKDSTLIMQLLRDNLTLWTSENQGDEGDAGEG-EN------- 5. S23179 NFSVFYYEILNSPEKACSLAKTAFDEAIAELDTLNEESYKDSTLIMQLLRDNLTLWTSENQGDEGDAGEG-EN------- 6. NP_003395 NFSVFYYEILNSPEKACSLAKTAFDEAIAELDTLSEESYKDSTLIMQLLRDNLTLWTSDTQGDDAEAGEGGEN------- 7. BAA11751 NFSVFYYEILNSPEKACSLAKTAFDEAIAELDTLSEESYKDSTLIMQLLRDNLTLWTSDTQGDDAEAGEGGEN------- 8. P29361 NFSVFYYEILNSPEKACSLAKTAFDEAIAELDTLSEESYKDSTLIMQLLRDNLTLWTSDTQGDEAEAGEGGEN------- 9. BAA13421 NFSVFYYEILNSPEKACSLAKTAFDEAIAELDTLSEESYKDSTLIIELLRDNLTLWTSDTQGDEAEAGEGGEN------- 10. NP_003397 NFSVFYYEILNSPEKACSLAKTAFDEAIAELDTLSEESYKDSTLIMQLLRDNLTLWTSDTQGDEAEAGEGGEN------- 11. S65013 NFSVFYYEILNSPEKACSLAKTAFDEAIAELDTLSEESYKDSTLIMQLLRDNLTLWTSDTQGDEAEAGEGGEN------- 12. P29309 NFSVFYYEILNSPEKACSLAKSAFDEAIRELDTLNEESYKDSTLIMQLLRDNLTLWTSENQGEEADNVEG-DN------- 13. AAC41252 NFSVFYYEILNCPDKACALAKAAFDEAIAELDTLSEESYKDSTLIMQLLRDNLTLWTSDTQGDEAEQGEGGEN------- 14. P31946 NYSVFYYEIQNAPEQACHLAKTAFDDAIAELDTLNEDSYKDSTLIMQLLRDNLTLWTSDQQDDD--GGEGN-N------- 15. P42655 NFSVFYYEILNSPDRACRLAKAAFDDAIAELDTLSEESYKDSTLIMQLLRDNLTLWTSDMQGDGEEQNKEALQDVEDENQ 16. P11576 NFSVFYYEIQNAPEQACLLAKQAFDDAIAELDTLNEDSYKDSTLIMQLLRDNLTLWTSDQQDEE--AGEGN--------- 17. P35214 NYSVFYYEIQNAPEQACHLAKTAFDDAIAELDTLNEDSYKDSTLIMQLLRDNLTLWTSDQQDDD--GGEGNN-------- 18. P29312 NFSVFYYEILNSPEKACSLAKTAFDEAIAELDTLSEESYKDSTLIMQLLRDNLTLWTSDTQGDEAEAGEGGEN------- 19. P35215 NFSVFYYEILNSPEKACSLAKTAFDEAIAELDTLSEESYKDSTLIMQLLRDNLTLWTSDTQGDEAEAGEGGEN------- 20. JC5384 NFSVFYYEILNSPEKACSLAKTAFDEAIAELDTLSEESYKDSTLIMQLLRDNLTLWTSDTQGDEAEAGEGGEN------- CONSENSUS NFSVFYYEILNSPEKACSLAKTAFDEAIAELDTLXEESYKDSTLIMQLLRDNLTLWTSD-QGDEXX-GEG-EN-------
Jacek Leluk, Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw University
10 20 30 40 50 60 70 80 90 100 110 120 P16436 IFGKII-RK--EIPAKIIYEDDQCLAFHDISPQAPTHFLVIPKKYISQISAAEDDDES--LLGHLMIVGKKCAADLGLKK------GYRMVVNEGSDGGQSVYHVHLHVLGGRQMNWPPG------ NP_071528.1 IFGKII-RK--EIPAKIIYEDDQCLAFHDISPQAPTHFLVIPKKYISQISAAEDDDES--LLGHLMIVGKKCAADLGLKK------GYRMVVNEGSDGGQSVYHVHLHVLGGRQMNWPPG------ A35350 IFGKII-RK--EIPAKIIYEDDQCLAFHDISPQAPTHFLVIPKKYISQISAAEDDDES--LLGHLMIVGKKCAADLGLKK------GYRMVVNEGSDGGQSVYHVHLHVLGGRQMNWPPG------ NP_787006.1 IFGKII-RK--EIPAKIIYEDDQCLAFHDISPQAPTHFLVIPKKYISEISAAEDDDES--LLGHLMIVGKKCAADLGLKK------GYRMVVNEGSDGGQSVYHVHLHVLGGRQMNWPPG------ P80912 IFGKII-RK--EIPAKIIFEDDQCLAFHDISPQAPTHFLVIPKKHISQISAAEDADES--LLGHLMIVGKKCAADLGLKK------GYRMVVNEGSDGGQSVYHVHLHVLGGRQMNWPPG------ NP_005331.1 IFGKII-RK--EIPAKIIFEDDRCLAFHDISPQAPTHFLVIPKKHISQISVAEDDDES--LLGHLMIVGKKCAADLGLNK------GYRMVVNEGSDGGQSVYHVHLHVLGGRQMHWPPG------ 1KPC IFGKII-RK--EIPAKIIFEDDRCLAFHDISPQAPTHFLVIPKKHISQISVAEDDDES--LLGHLMIVGKKCAADLGLNK------GYRMVVNEGSDGGQSVYHVHLHVLGGRQMHWPPG------ BAB15500.1 IFGKII-RE--EIPAKIIFEDDRCLAFHDISPQAPTHFLVIPKKHISQISVAEDDDES--LLGHLMIVGKKCAADLGLNK------GYRMVVNEGSDGGQSVYHVHLHVLGGRQMHWPPG------ XP_126166.1 IFGKII-RK--EIPAKIIFEDDRCLAFHDISPQAPTHFLVIPKKHISQISVADDDDES--LLGHLMIVGKKCAADLGLKR------GYRMVVNEGADGGQSVYHIHLHVLGGRQMNWPPG------ 3RHN IFGKII-RK--EIPAKIIFEDDQCLAFHDISPQAPTHFLVIPKKHISQISAAEDADES--LLGHLMIVGKKCAADLGLKK------GYRMVVNEGSDGGQSVYHVHLHVLGGRQMNWPPG------ AAN16460.1 IFGKII-RK--EIPANIIFEDEQCLAFHDISPQAPTHFLVIPKKPIVRLSEAEDSDES--LLGHLMIVGKKCAAELGLTN------GFRMVVNEGPEGGQSVYHVHLHVLGGRQLGWPPG------ BAA93454.1 IFGKII-RK--EIPANIIYEDEQCLAFHDISPQAPTHFLVIPKKPIVRLSEAEDSDES--LLGHLMIVGKKCAANLGLTN------GFRMVLNEGPEGGQSVYHVHLHILGGRQLGWPPG------ BAA94871.1 IFGKII-RK--EIPANIIYEDEQCLAFHDISPQAPTHFLVIPKKPIVRLSEAEDSDES--LLGHLMIVGKKCAANLGLTN------GFRMVLNEGPEGGQSVYHVHLHILGGRQLGWPPG------ XP_294311.1 VFGKIIC-K--EIPAKIIFEDDQCLAFHDTSPQAPTRFLLISKKHISQISAAEDNDES--LLGHLMIVGKKCAADLGLNK------GYQMVVNKGSDGGQSVCQVHLHVLGGWQMHWPPG------ XP_345534.1 IFGKII-RK--EILAKIIFEDDRCLAFHDISSQAPRHFLVIPKKHISQVSVADDDDES--LLGHLMIVGKKCAADLGLKR------GYRMVANEGADEG--WGQSVYHTSSMSLEVGR-------- NP_608711.3 IFGKIL-RK--EIPCKFIHEDDKCVAFHDVAPQAPTHFLVIPRKPIAQLSLAEDGDAD--LLGHLMLVGRKVAKELGLAD------GYRVVINNGKHGAQSVYHLHLHFLGGRQMQWPPG------ NP_722836.1 IFGKIL-RK--EIPCKFIHEDDKCVAFHDVAPQAPTHFLVIPRKPIAQLSLAEDGDAD--LLGHLMLVGRKVAKELGLAD------GYRVVINNGKHGAQSVYHLHLHFLGGRQMQWPPG------ XP_316373.1 IFGKIL-RK--EIPCTFIYEDDKCVAFNDVAPQAPVHFLVIPRKTIPQLSKATEEDEA--LLGHLMLVGKKVAAEQGMEE------GFRVVINDGKNGAQSVYHLHLHFLGGRQMKWPPG------ XP_143732.1 IFSRILDR-SL--PADILYEDQQCLVFRDVAPQAPVHFLVIPRKPIPRISQAEEDDQQ--LLGHLLLVAKKIAQAQGLKD------GYRLVVNDGKMGAQSVYHLHIHVLGGRQLQWPPG------ XP_233377.2 IFSRILDR-SL--PADILYEDHQCLVFRDVAPQAPVHFLVIPRKPIPRISQAEEDDQQ--LLGHLLLVAKKIAQAEGLKD------GYRLVVNDGKMGAQSVYHLHIHVLGGRQLQWPPG------ NP_492056.1 LFGKII-RK--EIPAKIIFEDDEALAFHDVSPQAPIHFLVIPKRRIDMLENAVDSDAA--LIGKLMVTASKVAKQLGMAN------GYRVVVNNGKDGAQSVFHLHLHVLGGRQLQWPPG------ NP_115982. IFSRILD-KSL--PADILYEDQQCLVFRDVAPQAPVHFLVIPKKPIPRISQAEEEDQQ--LLGHLLLVAKQTAKAEGLGD------GYRLVINDGKLGAQSVYHLHIHVLGGRQLQWPPG------ AAL40394.1 IFSRILD-KSL--PADILYEDQQCLVFRDVAPQAPVHFLVIPKKPIPRISQAEEEDQQ--LLGHLLLVAKQTAKAEGLGD------GYRLVINDGKLGAQSVYHLHIHVLGGRQLQWPPG------ NP_681787.1 IFSRII-RR--EIPADIVHEDELCLAFRDINPQAPVHILVIPKKPIPQLSLAEPEDHR--VLGHLLLTAKRIAEAEGLTN------GYRVVINNGPDGGQTVYHLHLHLLGGRPMQWPPG------ NP_488127.1 IFSKII-RR--EIPANIVYEDDLALAFKDVHPQAPVHILVIPKQPLAKLSDADSHDHA--LLGHLLLTAKRVAQEAGLEN------GYRVVINNGNDGGQTVYHLHLHILGGRPMAWPPG------ NP_776765.1 IFSRILDR-SL--PADILYEDQQCLAFRDVAPQAPVHFLVIPKKPIPRISQAEEEDQQ--LLGHLLLVAKETAKAEGLG-D-----GYRLVINDGKLGAQSVYHLHIHVLGGRQLQWPPG------ NP_440841.1 IFSKII-RR--EIPAAIVYEDDLCLAFKDVNPQAPVHVLLIPKKPLPQLSAATPEDHA--LLGHLLLKAKEVAADLGIG-DQ-----FRLVINNGAEVGQTVFHLHLHILGGRPFSWPPG------ NP_790447.1 LFTKIINR---EIPAKIIYEDDQVLAFHDIAPQAPVHFLVIPKKPIRTLNDLTEEDKG--LAGHILFTAQRLAIELGC--EE----GFRVVMNCNELGGQTVYHIHMHVLGQRQMSWPPG------ P32084 IFGKII-RR--EIPADIVYEDDLCLAFRDVAPQAPVHILVIPKQPIANLLEATAEHQA--LLGHLLLTVKAIAAQEGL-T-E----GYRTVINTGPAGGQTVYHLHIHLLGGRSLAWPPG------ NP_923875.1 VFGKIL-RR--EIPAAIVFEDERALAFRDINPQAPVHILVIPKRAIAQLEQVAPEDEA--LLGHLLYVAVQVARQEGL--DS----GYRLVVNNGVQGGQTVYHLHVHLLGGRMLAWPPG------ NP_869071.1 IFSKIIA-K--EIPADIVYEDDLCLAFRDIAPKAPTHILVIPKREIVSLADLTDEDQA--VMGRCVVVASKVAADEGLG-D-----GFRLVVNTGSDGGQEVPHVHFHLLGGRKMTWPPG------ NP_213096.1 IFCKIV-R-G-EVPAKKVYEDDKVLAFHDINPVAPVHILIIPKKHIMGIQTLEPEDE--CLVGHMFYVARKIAEDLGIAPDENLNKGYRLVFNVGKDAGQSVFHLHLHLIGGREMSWP-------- NP_742594.1 LFLKIINR---EIPADIIYEDDQILAFKDIAPAAPVHFLVIPKKHIRTLNDLTEEDKA--LAGHILFTAQRLAVEQGC--EE----GFRVVMNCNPKGGQTVYHIHMHVLGQRQMNWPPG------ AAN87419.1 IFCKIV-RK--EIPAQIVYEDDVVVAFKDINPAAPTHILIIPREHISSIAAAEASHQA--ILGQLLLASQKVTAALGI--E-PDKH--RLVINTGADAGQTVFHLHVHLLAGRNLGWPPG------ P42856 IFDKII--K--EIPSTVVYEDEKVLAFRDINPQAPTHILIIPKVKDGLTGLAKAEERHIEILGYLLYVAKVVAKQEGL--ED----GYRVVINDGPSGCQSVYHIHVHLLGGRQMNWPPG------ S45368 IFDKII-KK--EIPSTVVYEDEKVLAFRDINPQAPTHILIIPKVKDGLTGLAKAEERHIEILGYLLYVAKVVAKQEGL--ED----GYRVVINDGPSGCQSVYHIHVHLLGGRQMNWPPG------ NP_874474.1 IFSRIL-R-G-EIDCDEIYSDEMCLAFRDIQPQAPVHILVIPRKAIPSLREAEIQDES--LLGHLLLVSAKIAKLEGL-N----H--WRTVINSGSEAGQTVFHLHIHVIGGRKLNWPPG------ NP_711617.1 IFCKII-RK--EIPSKVVFENDEILAFYDISPQAPVHIVFIPKKHIPSLSEIENEDSH--LLGNILLQIRDTAKNLGFA--EN---GYRVVNNTGKNGGQTVFHIHFHLLAERRLHWPPG------ NP_896423.1 IFGKIL-R-G-DIPCDEVYSDDRCLAFRDIAPQAPVHVLVIPRQPIESLRSAGSGDEA--LLGHLLLVAARVARQEGL--ED-----FRTVINSGAAAGQTVFHLHVHVIGGRPLDWPPG------ P42855 IFGKIIS-K--EIPSTVVYEDDKVLAFRDITPQGPVHILLIPKVRDGLTGLFKAEERHIDILGRLLYTAKLVAKQEGL--DE----GFRIVINDGPQGCQSVYHIHVHLIGGRQMNWPPG------ NP_895423.1 IFGQML-R-G-EIPFDEVYSDERCLAFRDIQPQAPVHVLVIPRKPLDSLRAADSTDS--ELLGHLLLVAARVAKQEGL--DD-----FRTVINSGLEAGQTVFHLHVHVIGGRPLAWPPG------ NP_892188.1 IFSKIIN--G-EIPCEKLHEDELCLAFNDIASQAPVHFLVIPKKPLVSLCECLEEDR--DLLGHLLLIGKNIAKSKQL----KN---WRTVINTGEESGQTVFHLHIHFLAGRKMSWPPG------ NP_567038.1 IFDKIIS-K--EIPSTVVFEDDKVLAFRDITPQGPVHILLIPKVRDGLTGLSKAEERHIDILGRLLYTAKLVAKQEGL-AE-----GFRIVINDGPQGCQSVYHIHVHLIGGRQMNWPPG------ T49050 IFDKIIS-K--EIPSTVVFEDDKVLAFRDITPQGPVHILLIPKVRDGLTGLSKAEERHIDILGRLLYTAKLVAKQEGL-AE-----GFRIVINDGPQGCQSVYHIHVHLIGGRQMNWPPG------ NP_249347.1 LFCKIVA--G-EVPARKFYEDEEVVAFHDIGPQAPVHFLVIPKRHIPTLEHLTEADR--PLAGHILFTAQRLAREQGC--EE----GFRVVMNCNDLGGQTVHHIHMHVLGQRQMHWPPG------ NP_562940.1 IFCKIVA--G-EIPSKKIYEDDKVLAFHDISPEAPVHFLVIPKEHIASLNEVNEENAE--VFAHIFKTINKLVKEQEV-AED----GYRVVTNCGEQGGQTVGHIHFHVLGGRNLNWPPG------ NP_622615.1 IFCKIVN-K--EVPSNIVYEDDLVVAFRDINPQAPVHILIVPKEHIPTLLDVTEENKH--LISRAYMVAKEIAKKEGI--DEK---GYRIVTNCGKDGGQTVYHLHFHLLGGRFMTWPPG------ NP_782592.1 IFCKIVK--G-DIPSEKVYEDELILAFKDISPSAPTHVLVIPKKHIKNLNELSDNDAK--IISHIYIKIKELAQQLDI--NEK---GYRVVTNCGEQGGQTVEHIHFHLLGGRNLQWPPG------ ZP_00110753.1 IFSKII-RR--EIPVDIVYEDNLALAFKDIHPQAPVHILVIPKKPIPTLADAESQDHA--LLGHLLLTAKRVAEEAGL----KN--GYRVVINTGDDGGQTVYHLHLHILGGRQLDWPPG------ ZP_00128115.1 LFTKIIN-R--EIPAKIIYEDDQVLAFHDIAPQAPVHFLVIPKKPIRTLNDLTEEDKG--LAGHILFTAQRLALELGC--EE----GFRVVMNCNELGGQTVYHIHMHVLGQRQMTWPPG------ ZP_00072676.1 IFSKII-RR--EIPADIIYEDETTLAFKDINPQAPIHILVIPKKPIPNLANATSED-HI-LMGNLLLTAKQVAQEQGL-QN-----GYRVVINNGIDAGQTVFHLHLHILGGRPMQWPPG------ ZP_00092436.1 LFCKIAA--G-EIPAHKLYEDDLVVAFQDISPQAPVHFLVIPKRHIPTLNDLSEEDR-L-LAGHILLTAQRLAREQGC---EK---GFRAVMNCNEQGGQTVYHIHMHVLGQRQMHWPPG------ NP_797343.1 IFSKII-RK--EIPADILYQDDLVTAFRDINPRAPSHILIIPNKLIPTTNDVEAEDEA-M-MGRLFTVAKKLAKEEGIA-ED----GYRLILNCNPHGGQEVYHIHMHLLGGR----PLGPMVLS- NP_819816.1 VFCKIA--KG-EIGE-LIYEDKQVVAFNDAAPQAPIHILVIPHRHIETINDVTPGDE--DLLGHMVVVATRLAHDKNMAA-D----GYRLVMNCNRNGGQAVFHIHLHLLGGRQMHWPPG------ NP_760929.1 IFSKII-RK--EIPAQILFQDDLVTAFRDINPRAPKHILIIPNKLIPTVNDVEADDEA-M-MGRMFTVAKQLAKEEGIA-EE----GYRLIVNCNAHGGQEVYHIHMHLVGGK----PLGPMLLG- NP_704380.1 IFGKIA-R-G-EVPVDAVYEDDKVIAFNDIYPQAPVHIIVIPKRRDGLTRLSKAEEKHKEILGHLMWAVAEIVRKNNLG-D------FRLVVNNGPEACQSIYYLHLHILAKRQMKWPPG------ ZP_00122439.1 IFSKII-RK--EIPANIVYQDELVTAFRDISPQAPTHILIIPNKIIPTVNDVTSEDE-VT-LGRLFTVAAKLAEKEGIA-QD----GYRLIVNCNKHGGQEVYHLHMHLVGGEH----LGKMLAK- NP_347918.1 IFCKII--KG-EIPSSKVYEDEDVLAFNDISPAAPVHVLVIPKKHISSLNDINEENSKVIAHVFVV-IS-KLAKELGI--DED---GFRVVSNCGEAAGQTVHHVHFHLLGKKKFTWPPG------ ZP_00132345.1 IFSKII-RK--EIPANIVYQDELVTAFRDISPQAPTHILIIPNKIIPTVNDVTSEDE-VT-LGRLFTVAAKLAEKEGIAQD-----GYRLIVNCNKHGGQEVYHLHMHLVGGEH----LGKMLAK- IFGKII-RK--EIPAKIIYEDDQCLAFHDISPQAPVHFLVIPKKPIPQLSDAEDEDES--LLGHLLLVAKKVAADLGLK-------GYRVVINEGKDGGQSVYHLHLHVLGGRQMNWPPG------
Multiple alignment of the HIT family
Jacek Leluk, Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw University
The families of protein kinase inhibitors
• KCIP-1 - inhibit Ca dependent kinases• Ink4 – inhibit cyclin dependent kinases• Cip/Kip – inhibit cyclin dependent kinases• cAMP – inhibit cAMP dependent kinases• The HIT family ??? - supposed to inhibit
protein kinase C
Jacek Leluk, Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw University
Consensus sequences
KCIP-1
Cip/Kip
Ink4
Jacek Leluk, Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw University
Homology studies• Identity:KCIP – 1 -> 45 - 82% Ink4 -> 37 – 50%
Cip/Kip -> 33 – 40% (without the proline rich region) • Similarity (genetic relationships):KCIP-1 -> 84 - 90% Ink4 -> 55 - 60% Cip/Kip -> 50 - 62%
• The most conservative regions:KCIP-1 -> 14.3.3 protein motif: RNLLSVAY (positions: 44-51),
YKDSTLIMQLLRDNLTLWTS (positions:211-238) Ink4 -> Ankyrin motifs – a quadruple repeated motif (positions50-
67,81-101,117-134,149-169)Cip/Kip -> A domain reacting with the N-teminal site of the Cdk
kinase (31-40,64-68), the NLS motif (255-265,285,289).
Jacek Leluk, Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw University
0
10
20
30
40
50
60
70
1 2 3 4 5
Position variability
Per
cen
tag
e
R L S
Occurrence of six-codon amino acids in KCIP-1 family
Jacek Leluk, Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw University
0
10
20
30
40
50
60
70
1 2 3 4 5 6 7
Position variability
Per
cen
tag
e
R L S
Occurrence of six-codon amino acids in Ink4 family
Jacek Leluk, Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw University
Occurrence of six-codon amino acids in Cip/Kip family
0
10
20
30
40
50
60
70
1 2 3 4 5 6
Position variability
Per
cen
tag
e
R L S
Jacek Leluk, Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw University
T
IM
V
RS A
KN G P FL
L
DE R S
HQ CW
Y
Simplified (planar) diagram of genetic relationships between amino acids
In planar diagram the encoding role of the third codon position is ignored.
Only first two codon positions are taken into account.
Jacek Leluk, Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw University
T
IM
V
RS A
KN G P FL
L
DE R S
HQ CW
Y
Simplified (planar) diagram of genetic relationships between amino acids
The simplified planar diagram emphasizes the special encoding character of six-codon amino acids – Leu, Arg and Ser.
The six-codon amino acids may play the role the of „mutational passages” that are not liable to the selection restrictions.
These amino acids may influence on the variability range increase.
In fact the six-codon amino acids occur unusually frequent at very variable positions. This concerns especially serine, and to lesser extent – arginine.
Leucine does not show the correlation between the frequency of occurrence and variability range.
T
IM
V
RS A
KN G P FL
L
DE R S
HQ CW
Y
Jacek Leluk, Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw University
Frequency of six-codon amino acids as a function of position variability in randomly selected proteins of different origin and
nature
The results for 2686 residues at 606 corresponding positions
ALL SEQUENCES(2686 residues at 606 positions)
(discrete data)
0
20
40
60
80
100
1 2 3 4 5 6 7 8
Number of residues occurring at aligned position
% o
f occ
urre
nce
Ser
Arg
Leu
Jacek Leluk, Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw University
Studies on phylogenetic relationshipsProgram SSSS2
(Ela Gajewska and Jacek Leluk)
• Freely accessible Java application• Contact with the authors
[email protected], [email protected]• Phylogenetic trees generally reveal correlation with
observed similarity
Jacek Leluk, Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw University
Program SSSS2 The basic criteria used for analysis
unsignificant significant
Length of the sequence
Contribution of identities (%)
significant unsignificant
Distribution of identical positions
unsignificant significant
Jacek Leluk, Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw University
Pairwise similarity estimationby program SSSS2
(Sequence Similarity Significance Statement v. 2)
Jacek Leluk, Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw University
Pairwise similarity estimation
Jacek Leluk, Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw University
Phylograms
Cip inhibitor family
0.1
CAA59284.1
P46529
BAB39725.1
O19001
BAA19960.1
NP 113950.1
NP 004055.1
AAF69497.1
Q60439
NP 034005.1
AAM22491.1
BAA11015.1
NP 000067.1
I51683
AAC59775.1
NP 031695.1
NP 542960.1
NP 000380.1
AAG15411.1
O19002
AAH01935.1
AAC27627.1
AAN63876.1
KCIP inhibitor family
0.1
NP 003397
P29312
S65013
BAA11751
NP 003395
P35215
P29309
P29358
Q9CQV8
P35213
P29359
S23179
AAC41252
P42655
P11576
P31946
P35214
BAA13421
JC5384
P29361
Jacek Leluk, Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw University
Phylograms
Ink4 inhibitor family
0.1
CAB65455.1 BAA33541.1
AAA50282.1 NP 004927.2
CAC87045.1 CAC67498.1 NP 031696.1 NP 570825.1
O77617 AAG44950.1 AAG59801.1
NP 113738.1 AAC08963.1 AAB39600.1 P51480 AAC08962.1 AAD00229.1 AAD00227.1 AAD00228.1 AAD00230.1 AAD00236.1 AAD00231.1
NP 478104.1 AAC97110.1
AAL76343.1 NP 571977.1 NP 031697.1
CAC12811.1 Q60773 NP 034008.1 A57378 NP 001791.1 AAA85436.1
CAB65454.1 CAC87046.1 NP 000068.1 P42771 AAB60645.1 2002364A AAB32713.1
BAA33540.1 AAG01087.1
AAD00232.1 AAB94534.1
NP 478103.1 AAD14050.1
0.1
P04541NP 862822.1NP 006814.1
P27776A40536AAA40867.1AAH48244.1AAA39940.1
AAH36011.1AAK00638.1NP 115860.1Q9C010NP 861460.1NP 861459.1NP 036759.1AAA41879.1P27775NP 032889.2AAB59678.1B46707AAH61162.1Q04758A40962AAL90456.1
Q9Y2B9NP 008997.1NP 861521.1AAD55445.1NP 861520.1
AAQ17071.1AAQ17070.1
AAQ04718.1AAC09065.1
O70139NP 035236.1NP 703199.1
AAD30289.1AAA86697.1Q90641JC4128
NP 032888.1NP 446224.1AAA72716.1OKR BCI
AAH22265.1OKRBCI
cAMP inhibitor family
Jacek Leluk, Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw University
Phylograms
HIT inhibitor (?) family
0.1
NP 923875.1 NP 869071.1
NP 711617.1 NP 213096.1
ZP 00122439.1 ZP 00132345.1 NP 797343.1 NP 760929.1
P42855 NP 567038.1 T49050 P42856 S45368
NP 776765.1 NP 115982. AAL40394.1 XP 143732.1 XP 233377.2
AAN16460.1 BAA93454.1 BAA94871.1
XP 345534.1 XP 294311.1 XP 126166.1 BAB15500.1 NP 005331.1 1KPC P80912 3RHN P16436 NP 071528.1 A35350 NP 787006.1
XP 316373.1 NP 608711.3 NP 722836.1
NP 492056.1 NP 819816.1
NP 742594.1 NP 790447.1 ZP 00128115.1 ZP 00092436.1 NP 249347.1
NP 440841.1 NP 892188.1
P32084 NP 874474.1 NP 896423.1 NP 895423.1
NP 704380.1 AAN87419.1
NP 622615.1 NP 347918.1
NP 782592.1 NP 562940.1
NP 681787.1 ZP 00072676.1
ZP 00110753.1 NP 488127.1
Jacek Leluk, Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw University
Tertiary structures and correlated mutations within the inhibitor families
cAMP (PKA) inhibitor family (PKI5-24)
Ink4 inhibitor family
KCIP inhibitor family
HIT familyCip inhibitor family
Jacek Leluk, Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw University
Program Corm(written by Adam Górecki)
http://tarawa.icm.edu.pl/agorecki/corm
Location and characterization of correlated mutations occuring in proteins
Jacek Leluk, Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw University
Correlated mutations within the Cip/Kip inhibitor family
Jacek Leluk, Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw University
Correlated mutations within the Ink4 inhibitor family
Jacek Leluk, Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw University
Correlated mutations within the KCIP-1 inhibitor family
Jacek Leluk, Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw University
The results of this comparative analysis can be used in the process of the rational drug design against many pathophysiological states caused by wrong
functioning of kinases or their inhibitors.
This work was supported by European Centre of Excellence for Multi-scale Biomolecular Modelling, Bioinformatics and Applications
(project QLRI-CT-2002-90383) and by Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw University.
Jacek Leluk, Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw University
Zestawienie sekwencji (multiple alignment) 52 inhibitorów proteinaz typu Bowman-Birk sporządzone za pomocą algorytmu
semihomologii genetycznej Reszty konserwatywne i typowe wyszczególniono białymi literami na czarnym tle. Szare tło wskazuje aminokwasy
semihomologiczne. 3 10 20 30 40 50 60 P01055 ESSKPCCDQCACTKSNPPQCRCSDMRLNSCHSACKSCICALSYPAQCF-CVDITDFCYEP-CKP P01057 ESSKPCCDECACTKSIPPQCRCTDVRLNSCHSACSSCVCTFSIPAQCV-CVDMKDFCYAP-CKS P01056 QSSKPCCBHCACTKSIPPQCRCTDLRLDSCHSACKSCICTLSIPAQCV-CBBIBDFCYEP-CKS P01058 ESSKPCCDQCSCTKSMPPKCRCSDIRLNSCHSACKSCACTYSIPAKCF-CTDINDFCYEP-CKS P01059 ESSKPCCDLCTCTKSIPPQCHCNDMRLNSCHSACKSCICALSEPAQCF-CVDTTDFCYKS-CHN P01063 ESSKPCCDLCMCTASMPPQCHCADIRLNSCHSACDRCACTRSMPGQCR-CLDTTDFCYKP-CKS P17734 QSSKPCCRQCACTKSIPPQCRCSQVRLNSCHSACKSCACTFSIPAQCF-CGBIBBFCYKP-CKS P81483 -SSKPCCBHCACTKSIPPQCRCSBLRLNSCHSECKGCICTFSIPAQCI-CTDTNNFCYEP-CKS P81484 -SSKPCCBHCACTKSIPPQCRCSBLRLNSCHSECKGCICTFSIPAQCI-CTDTNNFCYEP-CKS P16343 ESSKPCCSSC-CTRSRPPQCQCTDVRLNSCHSACKSCMCTFSDPGMCS-CLDVTDFCYKP-CKS P01064 EYSKPCCDLCMCTRSMPPQCSCEDIRLNSCHSDCKSCMCTRSQPGQCR-CLDTNDFCYKP-CKS P82469 -SSGPCCDRCRCTKSEPPQCQCQDVRLNSCHSACEACVCSHSMPGLCS-CLDITHFCHEP-CKS P01061 ESSHPCCDLCLCTKSIPPQCQCADIRLDSCHSACKSCMCTRSMPGQCR-CLDTHDFCHKP-CKS P01062 ESSEPCCDSCDCTKSIPPECHCANIRLNSCHSACKSCICTRSMPGKCR-CLDTDDFCYKP-CES P01060 QSSPPCCBICVCTASIPPQCVCTBIRLBSCHSACKSCMCTRSMPGKCR-CLBTTBYCYKS-CKS 1BBI: ESSKPCCDQCACTKSNPPQCRCSDMRLNSCHSACKSCICALSYPAQCF-CVDITDFCYEP-CKP 1D6R:I ---KPCCDQCACTKSNPPQCRCSDMRLNSCHSACKSCICALSYPAQCF-CVDITDFCYEP-CK- 1DF9:C ESSEPCCDSCDCTKSIPPQCHCANIRLNSCHSACKSCICTRSMPGKCR-CLDTDDFCYKP-CES 1PI2: EYSKPCCDLCMCTRSMPPQCSCED-RINSCHSDCKSCMCTRSQPGQCR-CLDTNDFCYKP-CKS 1PBI:A DVKSACCDTCLCTKSNPPTCRCVDVGET-CHSACLSCICAYSNPPKCQ-CFDTQKFCYKQ-CHN AAB4719 ESSKPCCDQCTCTKSIPPQCRCTDVRLNSCHSACSSCVCTFSIPAQCV-CVDMKDFCYAP-CKS TISYC2 ESSKPCCDLCMCTASMPPQCHCADIRLNSCHSACDRCACTRSMPGQCR-CLDTTDFCYKP-CKS JC2225 ESSKPCCDLCMCTASMPPQCHCADIRLNSCHSACDRCACTRSMPGQCR-CLDTTDFCYKP-CKS TIZB2 ESSKPCCDQC-CTKSMPPKCRCSDIRLDSCHSACKSCACTYSIPAKCF-CTDINDFCYEP-CKS JC2073 ESSKPCCDECKCTKSEPPQCQCVDTRLESCHSACKLCLCALSFPAKCR-CVDTTDFCYKP-CKS JC2072 ESSKPCCDECKCTKSEPPQCQCVDTRLESCHSACKLCLCALSFPAKCR-CVDTTDFCYKP-CKS 0506164 ESSKPCCDQC-CTKSMPPKCRCSDIRLDSCHSACKSCACTYSIPAKCF-CTDINDFCYEP-CKS 0401177 ESSKPCCDLCMCTASMPPQCHCADIRLNSCHSACDRCACTRSMPGQCR-CLDTTDFCYKP-CKS 763679A ESSKPCCDLCMCTASMPPQCHCADIRLNSCHSACDRCACTRSMPGQCR-CLDTTDFCYKP-CKS TISYD2 EYSKPCCDLCMCTRSMPPQCSCEDIRLNSCHSDCKSCMCTRSQPGQCR-CLDTNDFCYKP-CKS 0907248 ESSEPCCDSCRCTKSIPPQCHCADIRLNSCHSACKSCMCTRSMPGKCR-CLDTDDFCYKP-CES 1102213 ESSEPCCDLCLCTKSIPPQCQCADIRLNSCHSACKSCMCTRSMPGQCH-CLDTHDFCHKP-CKS 1102213 ESSEPCCDLCLCTKSIPPQCQCADIRLNSCHSACKSCMCTRSMPGQCR-CLDTHDFCHKP-CKS 0404180 EYSKPCCDLCMCTRSMPPQCSCEDIRLNSCHSDCKSCMCTRSQPGQCR-CLDTNDFCYKP-CKS TIZB1B ESSHPCCDLCLCTKSIPPQCQCADIRLDSCHSACKSCMCTRSMPGQCH-CLDTHDFCHKP-CKS TIMB ESSEPCCDSCDCTKSKPPQCHCANIRLNSCHSACKSCICTRSMPGKCR-CLDTDDFCYKP-CES TIZB1P ESSHPCCDLCLCTKSIPPQCQCADIRLNSCHSACKSCMCTRSMPGQCR-CLDTHDFCHKP-CKS JC1066 ESSEPCCDSCDCTKSKPPQCHCANIRLNSCHSACKSCICTRSMPGKCR-CLDTDDFCTKP-CES Q41066 DVKSACCDTCLCTKSDPPTCRCVDVGET-CHSACDSCICALSYPPQCQ-CFDTHKFCYKA-CHN P80321 STTTACCDFCPCTRSIPPQCQCTDVREK-CHSACKSCLCTLSIPPQCH-CYDITDFCYPS-CR- Q41065 DVKSACCDTCLCTKSNPPTCRCVDVRET-CHSACDSCICAYSNPPKCQ-CFDTHKFCYKA-CHN P81705 --TSACCDKCFCTKSNPPICQCRDVGET-CHSACKFCICALSYPAQCH-CLDQNTFCYDK-CDS P56679 DVKSACCDTCLCTKSNPPTCRCVDVGET-CHSACLSCICAYSNPPKCQ-CFDTQKFCYKA-CHN P16346 --TTACCNFCPCTRSIPPQCRCTDIGET-CHSACKTCLCTKSIPPQCH-CADITNFCYPK-CN- P01065 DVKSACCDTCLCTRSQPPTCRCVDVGER-CHSACNHCVCNYSNPPQCQ-CFDTHKFCYKA-CHS P24661 DVKSACCDTCLCTKSEPPTCRCVDVGER-CHSACNSCVCRYSNPPKCQ-CFDTHKFCYKS-CHN P07679 KRPWECCDIAMCTRSIPPICRCVDKVDR-CSDACKDCEETEDN--RHV-CFDTYIGDPGPTCHD P19860 ERPWKCCDLQTCTKSIPAFCRCRDLLEQ-CSDACKECGKVRDSDPPRYICQDVYRGIPAPMCHE P22737 ERPWKCCDLQTCTKSIPAFCRCRDLLEQ-CSDACKECGKVRDSDPPRYICQDVYRGIPAPMCHE 220645 ES-EGCCDRCICTKSMPPQCHCHDVRLDSCHSDCETCICTRSYPAQCR-CADTTDFCYKP-C-S P09864 TRPWKCCDRAICTKSFPPMCRCMDMVEQ-CAATCKKCGPATSDSSRRV-CEDXY----------- P09863 KRPWKCCDQAVCTRSIPPICRCMDQVFE-CPSTCKACGPSVGDPSRRV-CQDQYV---------- KONSENSUS ESSKPCCDXCXCTKSIPPQCRCXDXRLNSCHSACKSCXCTRSXPXQCX-CXDTXDFCYKP-CKS
Thank you for your attention !
Bogdan Lesyng
AgataMeglicz
JacekLeluk
currently at:Leiden University Medical Center
The Netherlands