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Description:
Serine/threonine-protein kinase ATR (EC 2.7.1.37) (Ataxiatelangiectasia and Rad3-related protein) (FRAP-related protein 1).
Molecular weight: 3013
View which proteins in this organism that is involved with DNA Repair;
classified after biological processes (using data from the GOA project):
DNA repair( GO:0006281 )
Important dates:
29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
05-JUL-2004, sequence version 3.
07-MAR-2006, entry version 35.
Phylogenetic order:
Eukaryota Metazoa Chordata Craniata Vertebrata Euteleostomi Mammalia Eutheria Euarchontoglires Primates Catarrhini Hominidae Homo.
To calculate the pI (Isoelectric point - the pH where a protein has a neutral charge),
go to this page and enter the protein ID (e.g 3MG_ECOLI): http://us.expasy.org/tools/pi_tool.html
Links to references in other databases for protein ATR_HUMAN:
| Database | Pointer | Add. info#1 | Add. info#2 |
| EMBL | Y09077 | CAA70298.1 | - |
| EMBL | U76308 | AAC50929.1 | - |
| EMBL | U49844 | AAC50405.1 | - |
| EMBL | AF325699 | AAK26749.1 | - |
| Ensembl | ENSG00000175054 | Homo sapiens.1 | |
| HGNC | HGNC:882 | ATR.1 | |
| MIM | 210600 | phenotype. | |
| MIM | 601215 | gene. | |
| GO | GO:0004672 | F:protein kinase activity | TAS. |
| GO | GO:0007049 | P:cell cycle | TAS. |
| GO | GO:0000075 | P:cell cycle checkpoint | TAS. |
| GO | GO:0007275 | P:development | TAS. |
| GO | GO:0006281 | P:DNA repair | TAS. |
| InterPro | IPR011989 | ARM-like. | |
| InterPro | IPR003152 | FATC. | |
| InterPro | IPR000357 | HEAT. | |
| InterPro | IPR000403 | PI3/4_kinase_cat. | |
| InterPro | IPR011990 | TPR-like_helical. | |
| InterPro | IPR012993 | UME. | |
| Pfam | PF02260 | FATC | 1. |
| Pfam | PF02985 | HEAT | 2. |
| Pfam | PF00454 | PI3_PI4_kinase | 1. |
| Pfam | PF08064 | UME | 1. |
| SMART | SM00146 | PI3Kc | 1. |
| PROSITE | PS50077 | HEAT_REPEAT | 1. |
| PROSITE | PS00915 | PI3_4_KINASE_1 | FALSE_NEG. |
| PROSITE | PS00916 | PI3_4_KINASE_2 | 1. |
| PROSITE | PS50290 | PI3_4_KINASE_3 | 1. |
Keywords:
Alternative splicing; Chromosomal protein; DNA damage; DNA repair; DNA-binding; Dwarfism; Kinase; Manganese; Nuclear protein; Phosphorylation; Repeat; Serine/threonine-protein kinase; Transferase.
References:
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX MEDLINE=97133293; PubMed=8978690;
RA Bentley N.J., Holtzman D.A., Flaggs G., Keegan K.S., DeMaggio A.,
RA Ford J.C., Hoekstra M., Carr A.M.;
RT "The Schizosaccharomyces pombe rad3 checkpoint gene.";
RL EMBO J. 15:6641-6651(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=T-cell;
RX MEDLINE=96181495; PubMed=8610130; DOI=10.1073/pnas.93.7.2850;
RA Cimprich K.A., Shin T.B., Keith C.T., Schreiber S.L.;
RT "cDNA cloning and gene mapping of a candidate human cell cycle
RT checkpoint protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:2850-2855(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 433-526 (ISOFORMS 1 AND 2), AND TISSUE
RP SPECIFICITY.
RX MEDLINE=21363423; PubMed=11470508; DOI=10.1016/S0378-1119(01)00543-1;
RA Mannino J.L., Kim W.-J., Wernick M., Nguyen S.V., Braquet R.,
RA Adamson A.W., Den Z., Batzer M.A., Collins C.C., Brown K.D.;
RT "Evidence for alternate splicing within the mRNA transcript encoding
RT the DNA damage response kinase ATR.";
RL Gene 272:35-43(2001).
RN [4]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RA Keegan K.S., Holtzman D.A., Plug A.W., Christenson E.R.,
RA Brainerd E.E., Flaggs G., Bentley N.J., Taylor E.M., Meyn M.S.,
RA Moss S.B., Carr A.M., Ashley T., Hoekstra M.F.;
RT "The Atr and Atm protein kinases associate with different sites along
RT meiotically pairing chromosomes.";
RL Genes Dev. 10:2423-2437(1996).
RN [5]
RP ENZYME REGULATION.
RA Sarkaria J.N., Tibbetts R.S., Busby E.C., Kennedy A.P., Hill D.E.,
RA Abraham R.T.;
RT "Inhibition of phosphoinositide 3-kinase related kinases by the
RT radiosensitizing agent wortmannin.";
RL Cancer Res. 58:4375-4382(1998).
RN [6]
RP FUNCTION, AUTOPHOSPHORYLATION, AND MUTAGENESIS OF ASP-2475.
RX PubMed=9427750; DOI=10.1093/emboj/17.1.159;
RA Cliby W.A., Roberts C.J., Cimprich K.A., Stringer C.M., Lamb J.R.,
RA Schreiber S.L., Friend S.H.;
RT "Overexpression of a kinase-inactive ATR protein causes sensitivity to
RT DNA-damaging agents and defects in cell cycle checkpoints.";
RL EMBO J. 17:159-169(1998).
RN [7]
RP FUNCTION, AND MUTAGENESIS OF ASP-2494.
RX PubMed=9636169; DOI=10.1073/pnas.95.13.7445;
RA Wright J.A., Keegan K.S., Herendeen D.R., Bentley N.J., Carr A.M.,
RA Hoekstra M.F., Concannon P.;
RT "Protein kinase mutants of human ATR increase sensitivity to UV and
RT ionizing radiation and abrogate cell cycle checkpoint control.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:7445-7450(1998).
RN [8]
RP INTERACTION WITH HDAC2, AND IDENTIFICATION IN A COMPLEX CONTAINING
RP HDAC2 AND CHD4.
RX PubMed=10545197; DOI=10.1021/bi991614n;
RA Schmidt D.R., Schreiber S.L.;
RT "Molecular association between ATR and two components of the
RT nucleosome remodeling and deacetylating complex, HDAC2 and CHD4.";
RL Biochemistry 38:14711-14717(1999).
RN [9]
RP FUNCTION, AND MUTAGENESIS OF LYS-2327 AND ASP-2475.
RA Tibbetts R.S., Brumbaugh K.M., Williams J.M., Sarkaria J.N.,
RA Cliby W.A., Shieh S.-Y., Taya Y., Prives C., Abraham R.T.;
RT "A role for ATR in the DNA damage-induced phosphorylation of p53.";
RL Genes Dev. 13:152-157(1999).
RN [10]
RP COFACTOR, AND FUNCTION.
RX PubMed=10608806; DOI=10.1074/jbc.274.53.37538;
RA Kim S.-T., Lim D.-S., Canman C.E., Kastan M.B.;
RT "Substrate specificities and identification of putative substrates of
RT ATM kinase family members.";
RL J. Biol. Chem. 274:37538-37543(1999).
RN [11]
RP FUNCTION, AUTOPHOSPHORYLATION, MUTAGENESIS OF ASP-2494, AND ENZYME
RP REGULATION.
RX PubMed=10597277; DOI=10.1038/sj.onc.1203077;
RA Hall-Jackson C.A., Cross D.A.E., Morrice N., Smythe C.;
RT "ATR is a caffeine-sensitive, DNA-activated protein kinase with a
RT substrate specificity distinct from DNA-PK.";
RL Oncogene 18:6707-6713(1999).
RN [12]
RP FUNCTION.
RX MEDLINE=20317029; PubMed=10859164;
RA Liu Q., Guntuku S., Cui X.-S., Matsuoka S., Cortez D., Tamai K.,
RA Luo G., Carattini-Rivera S., DeMayo F., Bradley A., Donehower L.A.,
RA Elledge S.J.;
RT "Chk1 is an essential kinase that is regulated by Atr and required for
RT the G(2)/M DNA damage checkpoint.";
RL Genes Dev. 14:1448-1459(2000).
RN [13]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-2327.
RX PubMed=11114888; DOI=10.1101/gad.851000;
RA Tibbetts R.S., Cortez D., Brumbaugh K.M., Scully R., Livingston D.,
RA Elledge S.J., Abraham R.T.;
RT "Functional interactions between BRCA1 and the checkpoint kinase ATR
RT during genotoxic stress.";
RL Genes Dev. 14:2989-3002(2000).
RN [14]
RP FUNCTION.
RX PubMed=11673449; DOI=10.1074/jbc.C100569200;
RA Ward I.M., Chen J.;
RT "Histone H2AX is phosphorylated in an ATR-dependent manner in response
RT to replicational stress.";
RL J. Biol. Chem. 276:47759-47762(2001).
RN [15]
RP FUNCTION, AND INTERACTION WITH RAD17.
RX MEDLINE=21312051; PubMed=11418864; DOI=10.1038/35082110;
RA Bao S., Tibbetts R.S., Brumbaugh K.M., Fang Y., Richardson D.A.,
RA Ali A., Chen S.M., Abraham R.T., Wang X.-F.;
RT "ATR/ATM-mediated phosphorylation of human Rad17 is required for
RT genotoxic stress responses.";
RL Nature 411:969-974(2001).
RN [16]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH ATRIP.
RX MEDLINE=21578281; PubMed=11721054; DOI=10.1126/science.1065521;
RA Cortez D., Guntuku S., Qin J., Elledge S.J.;
RT "ATR and ATRIP: partners in checkpoint signaling.";
RL Science 294:1713-1716(2001).
RN [17]
RP FUNCTION.
RX PubMed=12526805; DOI=10.1016/S0092-8674(02)01113-3;
RA Casper A.M., Nghiem P., Arlt M.F., Glover T.W.;
RT "ATR regulates fragile site stability.";
RL Cell 111:779-789(2002).
RN [18]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=11865061; DOI=10.1128/MCB.22.6.1834-1843.2002;
RA Hammond E.M., Denko N.C., Dorie M.J., Abraham R.T., Giaccia A.J.;
RT "Hypoxia links ATR and p53 through replication arrest.";
RL Mol. Cell. Biol. 22:1834-1843(2002).
RN [19]
RP DNA-BINDING, AND MUTAGENESIS OF LYS-2327.
RX PubMed=12011431; DOI=10.1073/pnas.102167799;
RA Uensal-Kacmaz K., Makhov A.M., Griffith J.D., Sancar A.;
RT "Preferential binding of ATR protein to UV-damaged DNA.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:6673-6678(2002).
RN [20]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ASP-2475.
RX MEDLINE=22698999; PubMed=12814551; DOI=10.1016/S0960-9822(03)00376-2;
RA Barr S.M., Leung C.G., Chang E.E., Cimprich K.A.;
RT "ATR kinase activity regulates the intranuclear translocation of ATR
RT and RPA following ionizing radiation.";
RL Curr. Biol. 13:1047-1051(2003).
RN [21]
RP INTERACTION WITH CLSPN.
RX PubMed=12766152; DOI=10.1074/jbc.M301136200;
RA Chini C.C.S., Chen J.;
RT "Human claspin is required for replication checkpoint control.";
RL J. Biol. Chem. 278:30057-30062(2003).
RN [22]
RP DISEASE.
RX PubMed=12640452; DOI=10.1038/ng1129;
RA O'Driscoll M., Ruiz-Perez V.L., Woods C.G., Jeggo P.A., Goodship J.A.;
RT "A splicing mutation affecting expression of ataxia-telangiectasia and
RT Rad3-related protein (ATR) results in Seckel syndrome.";
RL Nat. Genet. 33:497-501(2003).
RN [23]
RP FUNCTION, INTERACTION WITH MSH2, AND MASS SPECTROMETRY.
RX PubMed=14657349; DOI=10.1073/pnas.2536810100;
RA Wang Y., Qin J.;
RT "MSH2 and ATR form a signaling module and regulate two branches of the
RT damage response to DNA methylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:15387-15392(2003).
RN [24]
RP FUNCTION, DNA-BINDING, AND IDENTIFICATION IN A COMPLEX WITH RPA AND
RP ATRIP.
RX PubMed=12791985; DOI=10.1126/science.1083430;
RA Zou L., Elledge S.J.;
RT "Sensing DNA damage through ATRIP recognition of RPA-ssDNA
RT complexes.";
RL Science 300:1542-1548(2003).
RN [25]
RP INTERACTION WITH BCR-ABL.
RX PubMed=15050919; DOI=10.1016/S1535-6108(04)00056-X;
RA Dierov J., Dierova R., Carroll M.;
RT "BCR/ABL translocates to the nucleus and disrupts an ATR-dependent
RT intra-S phase checkpoint.";
RL Cancer Cell 5:275-285(2004).
RN [26]
RP FUNCTION.
RX PubMed=14742437; DOI=10.1074/jbc.C300554200;
RA Ward I.M., Minn K., Chen J.;
RT "UV-induced ataxia-telangiectasia-mutated and Rad3-related (ATR)
RT activation requires replication stress.";
RL J. Biol. Chem. 279:9677-9680(2004).
RN [27]
RP DNA-BINDING, AND SUBCELLULAR LOCATION.
RX PubMed=14871897; DOI=10.1074/jbc.M314212200;
RA Dart D.A., Adams K.E., Akerman I., Lakin N.D.;
RT "Recruitment of the cell cycle checkpoint kinase ATR to chromatin
RT during S-phase.";
RL J. Biol. Chem. 279:16433-16440(2004).
RN [28]
RP FUNCTION.
RX PubMed=15314022; DOI=10.1101/gad.1196104;
RA Andreassen P.R., D'Andrea A.D., Taniguchi T.;
RT "ATR couples FANCD2 monoubiquitination to the DNA-damage response.";
RL Genes Dev. 18:1958-1963(2004).
RN [29]
RP FUNCTION.
RX PubMed=15496423; DOI=10.1093/hmg/ddh335;
RA Alderton G.K., Joenje H., Varon R., Borglum A.D., Jeggo P.A.,
RA O'Driscoll M.;
RT "Seckel syndrome exhibits cellular features demonstrating defects in
RT the ATR-signalling pathway.";
RL Hum. Mol. Genet. 13:3127-3138(2004).
RN [30]
RP FUNCTION, SUBUNIT, IDENTIFICATION IN A COMPLEX WITH ATRIP AND RPA1,
RP BINDING TO DNA, AND ENZYME REGULATION.
RX PubMed=14729973; DOI=10.1128/MCB.24.3.1292-1300.2003;
RA Uensal-Kacmaz K., Sancar A.;
RT "Quaternary structure of ATR and effects of ATRIP and replication
RT protein A on its DNA binding and kinase activities.";
RL Mol. Cell. Biol. 24:1292-1300(2004).
RN [31]
RP FUNCTION.
RX PubMed=15210935; DOI=10.1073/pnas.0403410101;
RA Cortez D., Glick G., Elledge S.J.;
RT "Minichromosome maintenance proteins are direct targets of the ATM and
RT ATR checkpoint kinases.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:10078-10083(2004).
RN [32]
RP INTERACTION WITH EEF1E1.
RX PubMed=15680327; DOI=10.1016/j.cell.2004.11.054;
RA Park B.-J., Kang J.W., Lee S.W., Choi S.-J., Shin Y.K., Ahn Y.H.,
RA Choi Y.H., Choi D., Lee K.S., Kim S.;
RT "The haploinsufficient tumor suppressor p18 upregulates p53 via
RT interactions with ATM/ATR.";
RL Cell 120:209-221(2005).
RN [33]
RP INTERACTION WITH ATRIP.
RX PubMed=15758953; DOI=10.1038/nature03442;
RA Falck J., Coates J., Jackson S.P.;
RT "Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of
RT DNA damage.";
RL Nature 434:605-611(2005).
Feature:
CHAIN 1 2644 Serine/threonine-protein kinase ATR.
/FTId=PRO_0000088844.
REPEAT 799 835 HEAT 1.
REPEAT 1329 1365 HEAT 2.
DOMAIN 2322 2567 PI3K/PI4K.
DOMAIN 2612 2644 FATC.
VARSPLIC 450 450 E -> D (in isoform 2).
/FTId=VSP_013305.
VARSPLIC 451 514 Missing (in isoform 2).
/FTId=VSP_013304.
MUTAGEN 2327 2327 K->R: Abolishes kinase activity.
MUTAGEN 2475 2475 D->A: Abolishes kinase activity;
increases sensitivity to IR and impairs
translocation to nuclear foci upon DNA
damage.
MUTAGEN 2494 2494 D->E: Abolishes kinase activity; reduces
cell viability, augments sensitivity to
IR and UV.
CONFLICT 92 92 A -> R (in Ref. 1).
Comments:
-!- FUNCTION: Serine/threonine protein kinase which activates
checkpoint signaling upon genotoxic stresses such as ionizing
radiation (IR), ultraviolet light (UV), or DNA replication
stalling, thereby acting as a DNA damage sensor. Recognizes the
substrate consensus sequence [S/T-Q]. Phosphorylates BRCA1, CHEK1,
MCM2, RAD17, RPA2, SMC1 and TP53/p53, which collectively inhibit
DNA replication and mitosis and promote DNA repair, recombination
and apoptosis. Phosphorylates Ser-139 of histone variant
H2AX/H2AFX at sites of DNA damage, thereby regulating DNA damage
response mechanism. Required for FANCD2 ubiquitination. Critical
for maintenance of fragile site stability and efficient regulation
of centrosome duplication.
-!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
-!- COFACTOR: Manganese.
-!- ENZYME REGULATION: Activated by DNA and inhibited by BCR-ABL
oncogene. Slightly activated by ATRIP. Inhibited by caffeine,
wortmannin and LY294002.
-!- SUBUNIT: Forms an heterodimer with ATRIP. Binds to DNA, and to UV-
damaged DNA with higher affinity. Interacts with RAD17, MSH2 and
HDAC2. Present in a complex containing ATRIP and RPA-coated
single-stranded DNA. Present in a complex containing CHD4 and
HDAC2. Interacts with BCR-ABL after genotoxic stress. Interacts
with EEF1E1. This interaction is enhanced by UV irradiation.
Interacts with CLSPN.
-!- SUBCELLULAR LOCATION: Nuclear. Depending on the cell type, it can
also be found in PML nuclear bodies. Recruited to chromatin during
S-phase. Redistributes to discrete nuclear foci upon DNA damage,
hypoxia or replication fork stalling.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=1;
IsoId=Q13535-1; Sequence=Displayed;
Name=2;
IsoId=Q13535-2; Sequence=VSP_013305, VSP_013304;
-!- TISSUE SPECIFICITY: Ubiquitous, with highest expression in testis.
Isoform 2 is found in pancreas, placenta and liver but not in
heart, testis and ovary.
-!- PTM: Phosphorylated; autophosphorylates in vitro.
-!- DISEASE: Defects in ATR are a cause of Seckel syndrome 1 (SCKL1)
[MIM:210600]. SCKL1 is a rare autosomal recessive disorder
characterized by growth retardation, microcephaly with mental
retardation, and a characteristic 'bird-headed' facial appearance.
-!- SIMILARITY: Belongs to the PI3/PI4-kinase family. ATM subfamily.
-!- SIMILARITY: Contains 1 FATC domain.
-!- SIMILARITY: Contains 2 HEAT repeats.
-!- SIMILARITY: Contains 1 PI3K/PI4K domain.
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Sequence length: 2644
MGEHGLELAS MIPALRELGS ATPEEYNTVV QKPRQILCQF IDRILTDVNV VAVELVKKTD
SQPTSVMLLD FIQHIMKSSP LMFVNVSGSH EAKGSCIEFS NWIITRLLRI AATPSCHLLH
KKICEVICSL LFLFKSKSPA IFGVLTKELL QLFEDLVYLH RRNVMGHAVE WPVVMSRFLS
QLDEHMGYLQ SAPLQLMSMQ NLEFIEVTLL MVLTRIIAIV FFRRQELLLW QIGCVLLEYG
SPKIKSLAIS FLTELFQLGG LPAQPASTFF SSFLELLKHL VEMDTDQLKL YEEPLSKLIK
TLFPFEAEAY RNIEPVYLNM LLEKLCVMFE DGVLMRLKSD LLKAALCHLL QYFLKFVPAG
YESALQVRKV YVRNICKALL DVLGIEVDAE YLLGPLYAAL KMESMEIIEE IQCQTQQENL
SSNSDGISPK RRRLSSSLNP SKRAPKQTEE IKHVDMNQKS ILWSALKQKA ESLQISLEYS
GLKNPVIEML EGIAVVLQLT ALCTVHCSHQ NMNCRTFKDC QHKSKKKPSV VITWMSLDFY
TKVLKSCRSL LESVQKLDLE ATIDKVVKIY DALIYMQVNS SFEDHILEDL CGMLSLPWIY
SHSDDGCLKL TTFAANLLTL SCRISDSYSP QAQSRCVFLL TLFPRRIFLE WRTAVYNWAL
QSSHEVIRAS CVSGFFILLQ QQNSCNRVPK ILIDKVKDDS DIVKKEFASI LGQLVCTLHG
MFYLTSSLTE PFSEHGHVDL FCRNLKATSQ HECSSSQLKA SVCKPFLFLL KKKIPSPVKL
AFIDNLHHLC KHLDFREDET DVKAVLGTLL NLMEDPDKDV RVAFSGNIKH ILESLDSEDG
FIKELFVLRM KEAYTHAQIS RNNELKDTLI LTTGDIGRAA KGDLVPFALL HLLHCLLSKS
ASVSGAAYTE IRALVAAKSV KLQSFFSQYK KPICQFLVES LHSSQMTALP NTPCQNADVR
KQDVAHQREM ALNTLSEIAN VFDFPDLNRF LTRTLQVLLP DLAAKASPAA SALIRTLGKQ
LNVNRREILI NNFKYIFSHL VCSCSKDELE RALHYLKNET EIELGSLLRQ DFQGLHNELL
LRIGEHYQQV FNGLSILASF ASSDDPYQGP RDIISPELMA DYLQPKLLGI LAFFNMQLLS
SSVGIEDKKM ALNSLMSLMK LMGPKHVSSV RVKMMTTLRT GLRFKDDFPE LCCRAWDCFV
RCLDHACLGS LLSHVIVALL PLIHIQPKET AAIFHYLIIE NRDAVQDFLH EIYFLPDHPE
LKKIKAVLQE YRKETSESTD LQTTLQLSMK AIQHENVDVR IHALTSLKET LYKNQEKLIK
YATDSETVEP IISQLVTVLL KGCQDANSQA RLLCGECLGE LGAIDPGRLD FSTTETQGKD
FTFVTGVEDS SFAYGLLMEL TRAYLAYADN SRAQDSAAYA IQELLSIYDC REMETNGPGH
QLWRRFPEHV REILEPHLNT RYKSSQKSTD WSGVKKPIYL SKLGSNFAEW SASWAGYLIT
KVRHDLASKI FTCCSIMMKH DFKVTIYLLP HILVYVLLGC NQEDQQEVYA EIMAVLKHDD
QHTINTQDIA SDLCQLSTQT VFSMLDHLTQ WARHKFQALK AEKCPHSKSN RNKVDSMVST
VDYEDYQSVT RFLDLIPQDT LAVASFRSKA YTRAVMHFES FITEKKQNIQ EHLGFLQKLY
AAMHEPDGVA GVSAIRKAEP SLKEQILEHE SLGLLRDATA CYDRAIQLEP DQIIHYHGVV
KSMLGLGQLS TVITQVNGVH ANRSEWTDEL NTYRVEAAWK LSQWDLVENY LAADGKSTTW
SVRLGQLLLS AKKRDITAFY DSLKLVRAEQ IVPLSAASFE RGSYQRGYEY IVRLHMLCEL
EHSIKPLFQH SPGDSSQEDS LNWVARLEMT QNSYRAKEPI LALRRALLSL NKRPDYNEMV
GECWLQSARV ARKAGHHQTA YNALLNAGES RLAELYVERA KWLWSKGDVH QALIVLQKGV
ELCFPENETP PEGKNMLIHG RAMLLVGRFM EETANFESNA IMKKYKDVTA CLPEWEDGHF
YLAKYYDKLM PMVTDNKMEK QGDLIRYIVL HFGRSLQYGN QFIYQSMPRM LTLWLDYGTK
AYEWEKAGRS DRVQMRNDLG KINKVITEHT NYLAPYQFLT AFSQLISRIC HSHDEVFVVL
MEIIAKVFLA YPQQAMWMMT AVSKSSYPMR VNRCKEILNK AIHMKKSLEK FVGDATRLTD
KLLELCNKPV DGSSSTLSMS THFKMLKKLV EEATFSEILI PLQSVMIPTL PSILGTHANH
ASHEPFPGHW AYIAGFDDMV EILASLQKPK KISLKGSDGK FYIMMCKPKD DLRKDCRLME
FNSLINKCLR KDAESRRREL HIRTYAVIPL NDECGIIEWV NNTAGLRPIL TKLYKEKGVY
MTGKELRQCM LPKSAALSEK LKVFREFLLP RHPPIFHEWF LRTFPDPTSW YSSRSAYCRS
TAVMSMVGYI LGLGDRHGEN ILFDSLTGEC VHVDFNCLFN KGETFEVPEI VPFRLTHNMV
NGMGPMGTEG LFRRACEVTM RLMRDQREPL MSVLKTFLHD PLVEWSKPVK GHSKAPLNET
GEVVNEKAKT HVLDIEQRLQ GVIKTRNRVT GLPLSIEGHV HYLIQEATDE NLLCQMYLGW
TPYM