SMG1_HUMAN
ID SMG1_HUMAN Reviewed; 3661 AA.
AC Q96Q15; O43305; Q13284; Q8NFX2; Q96QV0; Q96RW3;
DT 04-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT 08-FEB-2011, sequence version 3.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=Serine/threonine-protein kinase SMG1;
DE Short=SMG-1;
DE Short=hSMG-1;
DE EC=2.7.11.1;
DE AltName: Full=Lambda/iota protein kinase C-interacting protein {ECO:0000303|PubMed:8524286};
DE Short=Lambda-interacting protein {ECO:0000303|PubMed:8524286};
DE AltName: Full=Nonsense mediated mRNA decay-associated PI3K-related kinase SMG1 {ECO:0000312|HGNC:HGNC:30045};
GN Name=SMG1 {ECO:0000312|HGNC:HGNC:30045};
GN Synonyms=ATX {ECO:0000312|HGNC:HGNC:30045},
GN KIAA0421 {ECO:0000312|HGNC:HGNC:30045}, LIP {ECO:0000312|HGNC:HGNC:30045};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
RX PubMed=9566925; DOI=10.1128/mcb.18.5.3069;
RA Sanchez P., De Carcer G., Sandoval I.V., Moscat J., Diaz-Meco M.T.;
RT "Localization of atypical protein kinase C isoforms into lysosome-targeted
RT endosomes through interaction with p62.";
RL Mol. Cell. Biol. 18:3069-3080(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, PHOSPHORYLATION OF RENT1,
RP ALTERNATIVE SPLICING, ACTIVITY REGULATION, PHOSPHORYLATION, INTERACTION
RP WITH RENT1; UPF2 AND UPF3, AND MUTAGENESIS OF ASP-2335.
RX PubMed=11544179; DOI=10.1101/gad.913001;
RA Yamashita A., Ohnishi T., Kashima I., Taya Y., Ohno S.;
RT "Human SMG-1, a novel phosphatidylinositol 3-kinase-related protein kinase,
RT associates with components of the mRNA surveillance complex and is involved
RT in the regulation of nonsense-mediated mRNA decay.";
RL Genes Dev. 15:2215-2228(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION, PHOSPHORYLATION OF RENT1,
RP COFACTOR, ACTIVITY REGULATION, AND MUTAGENESIS OF ASP-2335.
RX PubMed=11331269; DOI=10.1074/jbc.c100144200;
RA Denning G., Jamieson L., Maquat L.E., Thompson E.A., Fields A.P.;
RT "Cloning of a novel phosphatidylinositol kinase-related kinase:
RT characterization of the human SMG-1 RNA surveillance protein.";
RL J. Biol. Chem. 276:22709-22714(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, PHOSPHORYLATION OF TP53,
RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, ACTIVITY REGULATION, MUTAGENESIS
RP OF ASP-2335, AND VARIANTS CYS-144 AND LYS-612.
RX PubMed=15175154; DOI=10.1016/j.molcel.2004.05.005;
RA Brumbaugh K.M., Otterness D.M., Geisen C., Oliveira V., Brognard J., Li X.,
RA Lejeune F., Tibbetts R.S., Maquat L.E., Abraham R.T.;
RT "The mRNA surveillance protein hSMG-1 functions in genotoxic stress
RT response pathways in mammalian cells.";
RL Mol. Cell 14:585-598(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1674-3661.
RC TISSUE=Brain;
RX PubMed=9455477; DOI=10.1093/dnares/4.5.307;
RA Ishikawa K., Nagase T., Nakajima D., Seki N., Ohira M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. VIII. 78
RT new cDNA clones from brain which code for large proteins in vitro.";
RL DNA Res. 4:307-313(1997).
RN [7]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 2878-3661, TISSUE SPECIFICITY, AND
RP INTERACTION WITH PRKCI.
RX PubMed=8524286; DOI=10.1128/mcb.16.1.105;
RA Diaz-Meco M.T., Municio M.M., Sanchez P., Lozano J., Moscat J.;
RT "Lambda-interacting protein, a novel protein that specifically interacts
RT with the zinc finger domain of the atypical protein kinase C isotype
RT lambda/iota and stimulates its kinase activity in vitro and in vivo.";
RL Mol. Cell. Biol. 16:105-114(1996).
RN [9]
RP DUPLICATION.
RX PubMed=11948212; DOI=10.1093/jhered/92.6.462;
RA Eichler E.E., Johnson M.E., Alkan C., Tuzun E., Sahinalp C., Misceo D.,
RA Archidiacono N., Rocchi M.;
RT "Divergent origins and concerted expansion of two segmental duplications on
RT chromosome 16.";
RL J. Hered. 92:462-468(2001).
RN [10]
RP INTERACTION WITH SMG5.
RX PubMed=14636577; DOI=10.1016/s1097-2765(03)00443-x;
RA Ohnishi T., Yamashita A., Kashima I., Schell T., Anders K.R., Grimson A.,
RA Hachiya T., Hentze M.W., Anderson P., Ohno S.;
RT "Phosphorylation of hUPF1 induces formation of mRNA surveillance complexes
RT containing hSMG-5 and hSMG-7.";
RL Mol. Cell 12:1187-1200(2003).
RN [11]
RP INTERACTION WITH RENT1; UPF2; EST1A AND UPF3B.
RX PubMed=12554878; DOI=10.1261/rna.2137903;
RA Chiu S.-Y., Serin G., Ohara O., Maquat L.E.;
RT "Characterization of human Smg5/7a: a protein with similarities to
RT Caenorhabditis elegans SMG5 and SMG7 that functions in the
RT dephosphorylation of Upf1.";
RL RNA 9:77-87(2003).
RN [12]
RP FUNCTION, INTERACTION WITH UPF2, AND IDENTIFICATION IN THE SURF COMPLEX.
RX PubMed=16452507; DOI=10.1101/gad.1389006;
RA Kashima I., Yamashita A., Izumi N., Kataoka N., Morishita R., Hoshino S.,
RA Ohno M., Dreyfuss G., Ohno S.;
RT "Binding of a novel SMG-1-Upf1-eRF1-eRF3 complex (SURF) to the exon
RT junction complex triggers Upf1 phosphorylation and nonsense-mediated mRNA
RT decay.";
RL Genes Dev. 20:355-367(2006).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-3550 AND SER-3556, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-3570, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [17]
RP CATALYTIC ACTIVITY, AND IDENTIFICATION IN THE SMG1C COMPLEX.
RX PubMed=19417104; DOI=10.1101/gad.1767209;
RA Yamashita A., Izumi N., Kashima I., Ohnishi T., Saari B., Katsuhata Y.,
RA Muramatsu R., Morita T., Iwamatsu A., Hachiya T., Kurata R., Hirano H.,
RA Anderson P., Ohno S.;
RT "SMG-8 and SMG-9, two novel subunits of the SMG-1 complex, regulate
RT remodeling of the mRNA surveillance complex during nonsense-mediated mRNA
RT decay.";
RL Genes Dev. 23:1091-1105(2009).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [19]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-173, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [20]
RP INTERACTION WITH TELO2 AND TTI1.
RX PubMed=20427287; DOI=10.1074/jbc.m110.121699;
RA Kaizuka T., Hara T., Oshiro N., Kikkawa U., Yonezawa K., Takehana K.,
RA Iemura S., Natsume T., Mizushima N.;
RT "Tti1 and Tel2 are critical factors in mammalian target of rapamycin
RT complex assembly.";
RL J. Biol. Chem. 285:20109-20116(2010).
RN [21]
RP INTERACTION WITH TTI1.
RX PubMed=20810650; DOI=10.1101/gad.1934210;
RA Hurov K.E., Cotta-Ramusino C., Elledge S.J.;
RT "A genetic screen identifies the Triple T complex required for DNA damage
RT signaling and ATM and ATR stability.";
RL Genes Dev. 24:1939-1950(2010).
RN [22]
RP INTERACTION WITH RUVBL1 AND RUVBL2.
RX PubMed=20371770; DOI=10.1126/scisignal.2000468;
RA Izumi N., Yamashita A., Iwamatsu A., Kurata R., Nakamura H., Saari B.,
RA Hirano H., Anderson P., Ohno S.;
RT "AAA+ proteins RUVBL1 and RUVBL2 coordinate PIKK activity and function in
RT nonsense-mediated mRNA decay.";
RL Sci. Signal. 3:RA27-RA27(2010).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-3573, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [24]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [25]
RP INTERACTION WITH SMG8 AND SMG9, AND ELECTRON MICROSCOPY OF THE SMG1C
RP COMPLEX.
RX PubMed=21245168; DOI=10.1101/gad.606911;
RA Arias-Palomo E., Yamashita A., Fernandez I.S., Nunez-Ramirez R., Bamba Y.,
RA Izumi N., Ohno S., Llorca O.;
RT "The nonsense-mediated mRNA decay SMG-1 kinase is regulated by large-scale
RT conformational changes controlled by SMG-8.";
RL Genes Dev. 25:153-164(2011).
RN [26]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-3550; SER-3556; SER-3570 AND
RP THR-3573, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [28]
RP INTERACTION WITH DHX34.
RX PubMed=25220460; DOI=10.1016/j.celrep.2014.08.020;
RA Hug N., Caceres J.F.;
RT "The RNA helicase DHX34 activates NMD by promoting a transition from the
RT surveillance to the decay-inducing complex.";
RL Cell Rep. 8:1845-1856(2014).
RN [29]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-3573, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [30]
RP IDENTIFICATION IN A COMPLEX WITH DHX34 AND UPF1, AND INTERACTION WITH DHX34
RP AND UPF1.
RX PubMed=26841701; DOI=10.1038/ncomms10585;
RA Melero R., Hug N., Lopez-Perrote A., Yamashita A., Caceres J.F., Llorca O.;
RT "The RNA helicase DHX34 functions as a scaffold for SMG1-mediated UPF1
RT phosphorylation.";
RL Nat. Commun. 7:10585-10585(2016).
RN [31]
RP INTERACTION WITH RUVBL1; RUVBL2; SMG8 AND SMG9.
RX PubMed=33205750; DOI=10.7554/elife.63042;
RA Lopez-Perrote A., Hug N., Gonzalez-Corpas A., Rodriguez C.F., Serna M.,
RA Garcia-Martin C., Boskovic J., Fernandez-Leiro R., Caceres J.F., Llorca O.;
RT "Regulation of RUVBL1-RUVBL2 AAA-ATPases by the nonsense-mediated mRNA
RT decay factor DHX34, as evidenced by Cryo-EM.";
RL Elife 9:0-0(2020).
RN [32]
RP VARIANTS [LARGE SCALE ANALYSIS] THR-35; CYS-126; CYS-144; TYR-151; ASN-160;
RP VAL-167; GLY-320; SER-465; ARG-546; SER-588; LYS-612; CYS-753; CYS-809;
RP CYS-812; ILE-829; ASP-832; GLY-952; SER-969; LEU-1016; GLN-1029; SER-1072;
RP HIS-1103; ARG-1275; PRO-1292; VAL-1332; PRO-1358; THR-1418; CYS-2171;
RP SER-2258; LYS-2345; GLU-2730; SER-2889; ALA-2899; THR-3239 AND GLN-3583.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Serine/threonine protein kinase involved in both mRNA
CC surveillance and genotoxic stress response pathways. Recognizes the
CC substrate consensus sequence [ST]-Q. Plays a central role in nonsense-
CC mediated decay (NMD) of mRNAs containing premature stop codons by
CC phosphorylating UPF1/RENT1. Recruited by release factors to stalled
CC ribosomes together with SMG8 and SMG9 (forming the SMG1C protein kinase
CC complex), and UPF1 to form the transient SURF (SMG1-UPF1-eRF1-eRF3)
CC complex. In EJC-dependent NMD, the SURF complex associates with the
CC exon junction complex (EJC) through UPF2 and allows the formation of an
CC UPF1-UPF2-UPF3 surveillance complex which is believed to activate NMD.
CC Also acts as a genotoxic stress-activated protein kinase that displays
CC some functional overlap with ATM. Can phosphorylate p53/TP53 and is
CC required for optimal p53/TP53 activation after cellular exposure to
CC genotoxic stress. Its depletion leads to spontaneous DNA damage and
CC increased sensitivity to ionizing radiation (IR). May activate PRKCI
CC but not PRKCZ. {ECO:0000269|PubMed:11331269,
CC ECO:0000269|PubMed:11544179, ECO:0000269|PubMed:15175154,
CC ECO:0000269|PubMed:16452507}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000269|PubMed:19417104};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000269|PubMed:19417104};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:11331269};
CC -!- ACTIVITY REGULATION: Inhibited by caffeine, LY294002 and wortmannin.
CC {ECO:0000269|PubMed:11331269, ECO:0000269|PubMed:11544179,
CC ECO:0000269|PubMed:15175154}.
CC -!- SUBUNIT: Component of the SMG1C complex composed of SMG1, SMG8 and
CC SMG9; the recruitment of SMG8 to SMG1 N-terminus induces a large
CC conformational change in the SMG1 C-terminal head domain containing the
CC catalytic domain (PubMed:33205750). Component of the transient SURF
CC (SMG1-UPF1-eRF1-eRF3) complex. Part of a complex composed of SMG1,
CC DHX34 and UPF1; within the complex DHX34 acts as a scaffolding protein
CC to facilitate SMG1 phosphorylation of UPF1 (PubMed:26841701). Interacts
CC with PRKCI. Interacts with TELO2 and TTI1. Interacts with RUVBL1 and
CC RUVBL2 (PubMed:33205750). Interacts with UPF2. Interacts with DHX34
CC (via C-terminus); the interaction is RNA-independent (PubMed:25220460,
CC PubMed:33205750). {ECO:0000269|PubMed:11544179,
CC ECO:0000269|PubMed:12554878, ECO:0000269|PubMed:14636577,
CC ECO:0000269|PubMed:16452507, ECO:0000269|PubMed:19417104,
CC ECO:0000269|PubMed:20371770, ECO:0000269|PubMed:20427287,
CC ECO:0000269|PubMed:20810650, ECO:0000269|PubMed:21245168,
CC ECO:0000269|PubMed:25220460, ECO:0000269|PubMed:26841701,
CC ECO:0000269|PubMed:33205750, ECO:0000269|PubMed:8524286}.
CC -!- INTERACTION:
CC Q96Q15; P11940: PABPC1; NbExp=2; IntAct=EBI-1049832, EBI-81531;
CC Q96Q15; Q9HAU5: UPF2; NbExp=7; IntAct=EBI-1049832, EBI-372073;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15175154}. Cytoplasm
CC {ECO:0000269|PubMed:15175154}. Note=Present in the chromatoid body.
CC {ECO:0000250|UniProtKB:Q8BKX6}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q96Q15-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96Q15-2; Sequence=VSP_017748;
CC Name=3;
CC IsoId=Q96Q15-3; Sequence=VSP_017747;
CC Name=4; Synonyms=BLIP;
CC IsoId=Q96Q15-4; Sequence=VSP_017746;
CC -!- TISSUE SPECIFICITY: Widely expressed, with highest level in heart and
CC skeletal muscle. Expressed in placenta, brain, lung and spleen, but not
CC in liver. {ECO:0000269|PubMed:15175154, ECO:0000269|PubMed:8524286}.
CC -!- PTM: Autophosphorylated. {ECO:0000305|PubMed:11331269,
CC ECO:0000305|PubMed:11544179, ECO:0000305|PubMed:15175154}.
CC -!- MISCELLANEOUS: This gene is located in a region of chromosome 16 that
CC contains 2 segmental duplications. Other genes that are highly related
CC to this exist, but they probably represent pseudogenes.
CC -!- SIMILARITY: Belongs to the PI3/PI4-kinase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA86535.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF186377; AAK58892.1; -; mRNA.
DR EMBL; AB061371; BAB70696.1; -; mRNA.
DR EMBL; AY014957; AAK00511.1; -; mRNA.
DR EMBL; AF395444; AAM73708.1; -; mRNA.
DR EMBL; AC092287; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AB007881; BAA24851.2; -; mRNA.
DR EMBL; U32581; AAA86535.2; ALT_INIT; mRNA.
DR CCDS; CCDS45430.1; -. [Q96Q15-1]
DR PIR; JC6084; JC6084.
DR RefSeq; NP_055907.3; NM_015092.4. [Q96Q15-1]
DR PDB; 6L53; EM; 3.63 A; A=1-3661.
DR PDB; 6L54; EM; 3.43 A; A=1-3661.
DR PDB; 6SYT; EM; 3.45 A; A=311-3661.
DR PDB; 6Z3R; EM; 2.97 A; A=259-3661.
DR PDB; 7PW4; EM; 3.27 A; A=311-3661.
DR PDB; 7PW5; EM; 3.40 A; A=311-3661.
DR PDB; 7PW6; EM; 3.05 A; A=766-3661.
DR PDB; 7PW7; EM; 3.59 A; A=311-3661.
DR PDB; 7PW8; EM; 2.82 A; A=311-3661.
DR PDB; 7PW9; EM; 3.12 A; A=311-3661.
DR PDBsum; 6L53; -.
DR PDBsum; 6L54; -.
DR PDBsum; 6SYT; -.
DR PDBsum; 6Z3R; -.
DR PDBsum; 7PW4; -.
DR PDBsum; 7PW5; -.
DR PDBsum; 7PW6; -.
DR PDBsum; 7PW7; -.
DR PDBsum; 7PW8; -.
DR PDBsum; 7PW9; -.
DR SMR; Q96Q15; -.
DR BioGRID; 116687; 77.
DR CORUM; Q96Q15; -.
DR IntAct; Q96Q15; 39.
DR MINT; Q96Q15; -.
DR STRING; 9606.ENSP00000402515; -.
DR BindingDB; Q96Q15; -.
DR ChEMBL; CHEMBL1795195; -.
DR GuidetoPHARMACOLOGY; 2201; -.
DR iPTMnet; Q96Q15; -.
DR MetOSite; Q96Q15; -.
DR PhosphoSitePlus; Q96Q15; -.
DR BioMuta; SMG1; -.
DR DMDM; 322510104; -.
DR EPD; Q96Q15; -.
DR jPOST; Q96Q15; -.
DR MassIVE; Q96Q15; -.
DR MaxQB; Q96Q15; -.
DR PaxDb; Q96Q15; -.
DR PeptideAtlas; Q96Q15; -.
DR PRIDE; Q96Q15; -.
DR ProteomicsDB; 77810; -. [Q96Q15-1]
DR ProteomicsDB; 77811; -. [Q96Q15-2]
DR ProteomicsDB; 77812; -. [Q96Q15-3]
DR ProteomicsDB; 77813; -. [Q96Q15-4]
DR Antibodypedia; 6280; 215 antibodies from 16 providers.
DR DNASU; 23049; -.
DR Ensembl; ENST00000446231.7; ENSP00000402515.3; ENSG00000157106.18. [Q96Q15-1]
DR GeneID; 23049; -.
DR KEGG; hsa:23049; -.
DR MANE-Select; ENST00000446231.7; ENSP00000402515.3; NM_015092.5; NP_055907.3.
DR UCSC; uc002dfm.4; human. [Q96Q15-1]
DR CTD; 23049; -.
DR DisGeNET; 23049; -.
DR GeneCards; SMG1; -.
DR HGNC; HGNC:30045; SMG1.
DR HPA; ENSG00000157106; Low tissue specificity.
DR MIM; 607032; gene.
DR neXtProt; NX_Q96Q15; -.
DR OpenTargets; ENSG00000157106; -.
DR PharmGKB; PA164725852; -.
DR VEuPathDB; HostDB:ENSG00000157106; -.
DR eggNOG; KOG0891; Eukaryota.
DR GeneTree; ENSGT00940000154776; -.
DR InParanoid; Q96Q15; -.
DR OMA; EAIIMRH; -.
DR OrthoDB; 26975at2759; -.
DR PhylomeDB; Q96Q15; -.
DR TreeFam; TF352560; -.
DR BRENDA; 2.7.11.1; 2681.
DR PathwayCommons; Q96Q15; -.
DR Reactome; R-HSA-975957; Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC).
DR SignaLink; Q96Q15; -.
DR SIGNOR; Q96Q15; -.
DR BioGRID-ORCS; 23049; 646 hits in 1124 CRISPR screens.
DR ChiTaRS; SMG1; human.
DR GeneWiki; SMG1_(gene); -.
DR GenomeRNAi; 23049; -.
DR Pharos; Q96Q15; Tchem.
DR PRO; PR:Q96Q15; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q96Q15; protein.
DR Bgee; ENSG00000157106; Expressed in upper leg skin and 192 other tissues.
DR ExpressionAtlas; Q96Q15; baseline and differential.
DR Genevisible; Q96Q15; HS.
DR GO; GO:0033391; C:chromatoid body; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0031931; C:TORC1 complex; IBA:GO_Central.
DR GO; GO:0031932; C:TORC2 complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004672; F:protein kinase activity; TAS:UniProtKB.
DR GO; GO:0004697; F:protein kinase C activity; EXP:Reactome.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0042162; F:telomeric DNA binding; IDA:BHF-UCL.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0006406; P:mRNA export from nucleus; TAS:UniProtKB.
DR GO; GO:0016242; P:negative regulation of macroautophagy; IBA:GO_Central.
DR GO; GO:0000184; P:nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; IDA:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:UniProtKB.
DR GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; IDA:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:2001020; P:regulation of response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0032204; P:regulation of telomere maintenance; IMP:BHF-UCL.
DR GO; GO:0031929; P:TOR signaling; IBA:GO_Central.
DR CDD; cd05170; PIKKc_SMG1; 1.
DR Gene3D; 1.10.1070.11; -; 1.
DR Gene3D; 1.25.10.10; -; 1.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR003152; FATC_dom.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000403; PI3/4_kinase_cat_dom.
DR InterPro; IPR036940; PI3/4_kinase_cat_sf.
DR InterPro; IPR018936; PI3/4_kinase_CS.
DR InterPro; IPR014009; PIK_FAT.
DR InterPro; IPR031559; SMG1.
DR InterPro; IPR035175; SMG1_N.
DR InterPro; IPR039414; SMG1_PIKKc.
DR Pfam; PF02260; FATC; 1.
DR Pfam; PF00454; PI3_PI4_kinase; 1.
DR Pfam; PF15785; SMG1; 1.
DR Pfam; PF17229; SMG1_N; 1.
DR SMART; SM01343; FATC; 1.
DR SMART; SM00146; PI3Kc; 1.
DR SUPFAM; SSF48371; SSF48371; 2.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51189; FAT; 1.
DR PROSITE; PS51190; FATC; 1.
DR PROSITE; PS00916; PI3_4_KINASE_2; 1.
DR PROSITE; PS50290; PI3_4_KINASE_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; ATP-binding; Cytoplasm;
KW DNA damage; DNA repair; Kinase; Manganese; Metal-binding;
KW Nonsense-mediated mRNA decay; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..3661
FT /note="Serine/threonine-protein kinase SMG1"
FT /id="PRO_0000229791"
FT DOMAIN 1283..1866
FT /note="FAT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00534"
FT REPEAT 1817..1852
FT /note="HEAT"
FT DOMAIN 2124..2463
FT /note="PI3K/PI4K catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT DOMAIN 3629..3661
FT /note="FATC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00534,
FT ECO:0000255|PROSITE-ProRule:PRU00535"
FT REGION 1..1977
FT /note="Interaction with SMG8 and SMG9"
FT /evidence="ECO:0000269|PubMed:21245168"
FT REGION 1..101
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 116..144
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1154..1175
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1898..1919
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2130..2136
FT /note="G-loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 2332..2340
FT /note="Catalytic loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 2352..2376
FT /note="Activation loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 3568..3591
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 25..67
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 68..82
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 87..101
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 128..142
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3568..3583
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 173
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 3550
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:17525332,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 3556
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17525332,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 3570
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 3573
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 3577
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q8BKX6"
FT VAR_SEQ 1..1269
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:9566925"
FT /id="VSP_017746"
FT VAR_SEQ 1..630
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:11331269"
FT /id="VSP_017747"
FT VAR_SEQ 1..140
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15175154"
FT /id="VSP_017748"
FT VARIANT 35
FT /note="A -> T (in dbSNP:rs12051350)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041623"
FT VARIANT 126
FT /note="R -> C (in dbSNP:rs752796432)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041624"
FT VARIANT 144
FT /note="S -> C (in dbSNP:rs766737607)"
FT /evidence="ECO:0000269|PubMed:15175154,
FT ECO:0000269|PubMed:17344846"
FT /id="VAR_041625"
FT VARIANT 151
FT /note="N -> Y (in dbSNP:rs750788715)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041626"
FT VARIANT 160
FT /note="D -> N"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041627"
FT VARIANT 167
FT /note="A -> V (in dbSNP:rs1382468496)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041628"
FT VARIANT 320
FT /note="D -> G"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041629"
FT VARIANT 465
FT /note="G -> S (in dbSNP:rs200419100)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041630"
FT VARIANT 546
FT /note="H -> R (in dbSNP:rs376234691)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041631"
FT VARIANT 588
FT /note="A -> S (in dbSNP:rs750840136)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041632"
FT VARIANT 612
FT /note="I -> K (in dbSNP:rs17842615)"
FT /evidence="ECO:0000269|PubMed:15175154,
FT ECO:0000269|PubMed:17344846"
FT /id="VAR_041633"
FT VARIANT 753
FT /note="S -> C (in dbSNP:rs569679854)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041634"
FT VARIANT 809
FT /note="S -> C (in dbSNP:rs919788709)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041635"
FT VARIANT 812
FT /note="R -> C (in dbSNP:rs1233400465)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041636"
FT VARIANT 829
FT /note="V -> I"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041637"
FT VARIANT 832
FT /note="N -> D (in dbSNP:rs80176913)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041638"
FT VARIANT 952
FT /note="A -> G (in dbSNP:rs555078480)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041639"
FT VARIANT 969
FT /note="N -> S (in dbSNP:rs1412788971)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041640"
FT VARIANT 1016
FT /note="F -> L (in dbSNP:rs1394431566)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041641"
FT VARIANT 1029
FT /note="R -> Q"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041642"
FT VARIANT 1072
FT /note="T -> S (in dbSNP:rs45516593)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041643"
FT VARIANT 1103
FT /note="N -> H (in dbSNP:rs563883658)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041644"
FT VARIANT 1275
FT /note="P -> R"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041645"
FT VARIANT 1292
FT /note="Q -> P (in dbSNP:rs375411122)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041646"
FT VARIANT 1332
FT /note="I -> V (in dbSNP:rs949474935)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041647"
FT VARIANT 1358
FT /note="S -> P"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041648"
FT VARIANT 1418
FT /note="R -> T (in dbSNP:rs17731779)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041649"
FT VARIANT 2171
FT /note="S -> C (in a breast pleomorphic lobular carcinoma
FT sample; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041650"
FT VARIANT 2258
FT /note="G -> S (in dbSNP:rs35572280)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041651"
FT VARIANT 2345
FT /note="M -> K (in dbSNP:rs56276814)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041652"
FT VARIANT 2730
FT /note="Q -> E (in dbSNP:rs34960798)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041653"
FT VARIANT 2889
FT /note="G -> S (in dbSNP:rs35952340)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041654"
FT VARIANT 2899
FT /note="P -> A (in dbSNP:rs55782217)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041655"
FT VARIANT 3239
FT /note="I -> T (in a breast infiltrating ductal carcinoma
FT sample; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041656"
FT VARIANT 3583
FT /note="K -> Q (in a breast infiltrating ductal carcinoma
FT sample; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041657"
FT MUTAGEN 2335
FT /note="D->A: Loss of function."
FT /evidence="ECO:0000269|PubMed:11331269,
FT ECO:0000269|PubMed:11544179, ECO:0000269|PubMed:15175154"
FT CONFLICT 14
FT /note="G -> GGGGG (in Ref. 2; BAB70696)"
FT /evidence="ECO:0000305"
FT CONFLICT 20
FT /note="K -> N (in Ref. 2; BAB70696)"
FT /evidence="ECO:0000305"
FT CONFLICT 22
FT /note="P -> S (in Ref. 2; BAB70696)"
FT /evidence="ECO:0000305"
FT CONFLICT 40
FT /note="D -> G (in Ref. 2; BAB70696)"
FT /evidence="ECO:0000305"
FT CONFLICT 686
FT /note="S -> A (in Ref. 2; BAB70696)"
FT /evidence="ECO:0000305"
FT CONFLICT 743
FT /note="K -> R (in Ref. 2; BAB70696)"
FT /evidence="ECO:0000305"
FT CONFLICT 1193
FT /note="C -> F (in Ref. 2; BAB70696)"
FT /evidence="ECO:0000305"
FT CONFLICT 2009
FT /note="K -> R (in Ref. 2; BAB70696)"
FT /evidence="ECO:0000305"
FT CONFLICT 2077
FT /note="S -> N (in Ref. 1; AAK58892)"
FT /evidence="ECO:0000305"
FT HELIX 38..42
FT /evidence="ECO:0007829|PDB:6L54"
FT HELIX 62..69
FT /evidence="ECO:0007829|PDB:6L54"
FT HELIX 70..73
FT /evidence="ECO:0007829|PDB:6L54"
FT HELIX 81..88
FT /evidence="ECO:0007829|PDB:6L54"
FT TURN 94..96
FT /evidence="ECO:0007829|PDB:6L54"
FT HELIX 97..102
FT /evidence="ECO:0007829|PDB:6L54"
FT HELIX 103..105
FT /evidence="ECO:0007829|PDB:6L54"
FT STRAND 110..113
FT /evidence="ECO:0007829|PDB:6L54"
FT HELIX 114..117
FT /evidence="ECO:0007829|PDB:6L54"
FT HELIX 124..141
FT /evidence="ECO:0007829|PDB:6L54"
FT STRAND 143..148
FT /evidence="ECO:0007829|PDB:6L54"
FT HELIX 151..153
FT /evidence="ECO:0007829|PDB:6L54"
FT HELIX 154..162
FT /evidence="ECO:0007829|PDB:6L54"
FT TURN 163..167
FT /evidence="ECO:0007829|PDB:6L54"
FT HELIX 171..174
FT /evidence="ECO:0007829|PDB:6L54"
FT HELIX 178..181
FT /evidence="ECO:0007829|PDB:6L54"
FT HELIX 189..198
FT /evidence="ECO:0007829|PDB:6L54"
FT TURN 199..201
FT /evidence="ECO:0007829|PDB:6L54"
FT HELIX 202..204
FT /evidence="ECO:0007829|PDB:6L54"
FT HELIX 211..222
FT /evidence="ECO:0007829|PDB:6L54"
FT HELIX 230..245
FT /evidence="ECO:0007829|PDB:6L54"
FT HELIX 261..274
FT /evidence="ECO:0007829|PDB:6Z3R"
FT HELIX 281..292
FT /evidence="ECO:0007829|PDB:6Z3R"
FT HELIX 297..306
FT /evidence="ECO:0007829|PDB:6Z3R"
FT HELIX 307..309
FT /evidence="ECO:0007829|PDB:6Z3R"
FT HELIX 314..321
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 322..324
FT /evidence="ECO:0007829|PDB:6L54"
FT HELIX 326..330
FT /evidence="ECO:0007829|PDB:6L54"
FT HELIX 336..346
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 356..373
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 380..387
FT /evidence="ECO:0007829|PDB:6L54"
FT HELIX 389..394
FT /evidence="ECO:0007829|PDB:6L54"
FT HELIX 395..411
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 421..424
FT /evidence="ECO:0007829|PDB:6L54"
FT HELIX 429..443
FT /evidence="ECO:0007829|PDB:7PW8"
FT TURN 445..447
FT /evidence="ECO:0007829|PDB:7PW9"
FT HELIX 450..466
FT /evidence="ECO:0007829|PDB:7PW8"
FT STRAND 469..471
FT /evidence="ECO:0007829|PDB:6Z3R"
FT HELIX 475..486
FT /evidence="ECO:0007829|PDB:7PW8"
FT STRAND 490..492
FT /evidence="ECO:0007829|PDB:6Z3R"
FT HELIX 494..510
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 517..523
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 529..532
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 533..535
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 539..552
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 558..582
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 590..592
FT /evidence="ECO:0007829|PDB:7PW4"
FT HELIX 595..597
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 598..600
FT /evidence="ECO:0007829|PDB:6L54"
FT HELIX 604..622
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 625..630
FT /evidence="ECO:0007829|PDB:6L54"
FT STRAND 634..636
FT /evidence="ECO:0007829|PDB:7PW9"
FT HELIX 638..644
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 647..650
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 653..656
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 658..673
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 674..678
FT /evidence="ECO:0007829|PDB:7PW8"
FT TURN 679..681
FT /evidence="ECO:0007829|PDB:7PW9"
FT TURN 700..705
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 706..718
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 725..741
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 746..753
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 755..766
FT /evidence="ECO:0007829|PDB:7PW8"
FT STRAND 768..771
FT /evidence="ECO:0007829|PDB:6Z3R"
FT HELIX 773..785
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 792..805
FT /evidence="ECO:0007829|PDB:7PW8"
FT STRAND 807..810
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 811..821
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 826..829
FT /evidence="ECO:0007829|PDB:7PW8"
FT STRAND 831..833
FT /evidence="ECO:0007829|PDB:6L54"
FT HELIX 836..850
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 859..870
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 882..889
FT /evidence="ECO:0007829|PDB:7PW8"
FT TURN 890..895
FT /evidence="ECO:0007829|PDB:6L54"
FT HELIX 903..905
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 909..926
FT /evidence="ECO:0007829|PDB:7PW8"
FT TURN 927..929
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 936..955
FT /evidence="ECO:0007829|PDB:7PW8"
FT TURN 962..964
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 970..998
FT /evidence="ECO:0007829|PDB:7PW8"
FT STRAND 1002..1005
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 1010..1018
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 1020..1040
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 1044..1057
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 1068..1082
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 1086..1096
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 1107..1114
FT /evidence="ECO:0007829|PDB:7PW8"
FT TURN 1115..1117
FT /evidence="ECO:0007829|PDB:6L54"
FT HELIX 1118..1133
FT /evidence="ECO:0007829|PDB:7PW8"
FT STRAND 1134..1136
FT /evidence="ECO:0007829|PDB:6L54"
FT HELIX 1144..1150
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 1180..1196
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 1200..1215
FT /evidence="ECO:0007829|PDB:7PW8"
FT TURN 1216..1218
FT /evidence="ECO:0007829|PDB:6Z3R"
FT HELIX 1228..1239
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 1242..1249
FT /evidence="ECO:0007829|PDB:7PW8"
FT STRAND 1251..1255
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 1282..1304
FT /evidence="ECO:0007829|PDB:7PW8"
FT STRAND 1315..1317
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 1318..1331
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 1333..1340
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 1348..1366
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 1371..1373
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 1379..1382
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 1391..1406
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 1407..1409
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 1418..1433
FT /evidence="ECO:0007829|PDB:7PW8"
FT TURN 1434..1436
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 1438..1449
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 1459..1466
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 1467..1479
FT /evidence="ECO:0007829|PDB:6L54"
FT HELIX 1480..1494
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 1497..1511
FT /evidence="ECO:0007829|PDB:7PW8"
FT STRAND 1514..1516
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 1518..1534
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 1536..1550
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 1560..1569
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 1587..1590
FT /evidence="ECO:0007829|PDB:6Z3R"
FT STRAND 1591..1593
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 1596..1611
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 1616..1636
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 1640..1648
FT /evidence="ECO:0007829|PDB:6Z3R"
FT HELIX 1651..1659
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 1668..1677
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 1686..1695
FT /evidence="ECO:0007829|PDB:6SYT"
FT HELIX 1708..1719
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 1720..1725
FT /evidence="ECO:0007829|PDB:6Z3R"
FT HELIX 1729..1740
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 1742..1756
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 1782..1798
FT /evidence="ECO:0007829|PDB:7PW8"
FT STRAND 1801..1803
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 1804..1813
FT /evidence="ECO:0007829|PDB:7PW8"
FT TURN 1818..1821
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 1823..1828
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 1829..1831
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 1836..1849
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 1853..1855
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 1857..1864
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 1925..1938
FT /evidence="ECO:0007829|PDB:7PW8"
FT STRAND 1939..1941
FT /evidence="ECO:0007829|PDB:6L54"
FT HELIX 1942..1957
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 1963..1977
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 1980..1992
FT /evidence="ECO:0007829|PDB:6Z3R"
FT HELIX 2011..2023
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 2036..2044
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 2047..2054
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 2069..2082
FT /evidence="ECO:0007829|PDB:7PW8"
FT STRAND 2085..2087
FT /evidence="ECO:0007829|PDB:6L54"
FT STRAND 2090..2092
FT /evidence="ECO:0007829|PDB:7PW8"
FT TURN 2097..2101
FT /evidence="ECO:0007829|PDB:7PW9"
FT STRAND 2120..2124
FT /evidence="ECO:0007829|PDB:7PW8"
FT STRAND 2126..2130
FT /evidence="ECO:0007829|PDB:7PW8"
FT STRAND 2132..2136
FT /evidence="ECO:0007829|PDB:7PW8"
FT STRAND 2138..2144
FT /evidence="ECO:0007829|PDB:7PW8"
FT STRAND 2149..2157
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 2161..2175
FT /evidence="ECO:0007829|PDB:7PW8"
FT TURN 2176..2179
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 2180..2182
FT /evidence="ECO:0007829|PDB:7PW8"
FT STRAND 2195..2197
FT /evidence="ECO:0007829|PDB:7PW8"
FT STRAND 2199..2201
FT /evidence="ECO:0007829|PDB:7PW8"
FT STRAND 2203..2206
FT /evidence="ECO:0007829|PDB:7PW8"
FT STRAND 2212..2214
FT /evidence="ECO:0007829|PDB:6Z3R"
FT HELIX 2215..2231
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 2249..2262
FT /evidence="ECO:0007829|PDB:7PW8"
FT STRAND 2272..2274
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 2277..2290
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 2295..2303
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 2307..2331
FT /evidence="ECO:0007829|PDB:7PW8"
FT STRAND 2340..2343
FT /evidence="ECO:0007829|PDB:7PW8"
FT TURN 2345..2347
FT /evidence="ECO:0007829|PDB:7PW8"
FT STRAND 2350..2352
FT /evidence="ECO:0007829|PDB:7PW8"
FT TURN 2356..2360
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 2361..2363
FT /evidence="ECO:0007829|PDB:7PW8"
FT STRAND 2364..2367
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 2377..2381
FT /evidence="ECO:0007829|PDB:7PW8"
FT STRAND 2384..2386
FT /evidence="ECO:0007829|PDB:6L54"
FT STRAND 2388..2390
FT /evidence="ECO:0007829|PDB:6Z3R"
FT HELIX 2391..2405
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 2407..2418
FT /evidence="ECO:0007829|PDB:7PW8"
FT STRAND 2422..2424
FT /evidence="ECO:0007829|PDB:6L54"
FT HELIX 3608..3620
FT /evidence="ECO:0007829|PDB:7PW8"
FT STRAND 3627..3629
FT /evidence="ECO:0007829|PDB:7PW6"
FT HELIX 3633..3645
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 3647..3651
FT /evidence="ECO:0007829|PDB:7PW8"
FT HELIX 3655..3657
FT /evidence="ECO:0007829|PDB:7PW8"
SQ SEQUENCE 3661 AA; 410501 MW; 216A55F3121F5829 CRC64;
MSRRAPGSRL SSGGGGGGTK YPRSWNDWQP RTDSASADPD NLKYSSSRDR GGSSSYGLQP
SNSAVVSRQR HDDTRVHADI QNDEKGGYSV NGGSGENTYG RKSLGQELRV NNVTSPEFTS
VQHGSRALAT KDMRKSQERS MSYSDESRLS NLLRRITRED DRDRRLATVK QLKEFIQQPE
NKLVLVKQLD NILAAVHDVL NESSKLLQEL RQEGACCLGL LCASLSYEAE KIFKWIFSKF
SSSAKDEVKL LYLCATYKAL ETVGEKKAFS SVMQLVMTSL QSILENVDTP ELLCKCVKCI
LLVARCYPHI FSTNFRDTVD ILVGWHIDHT QKPSLTQQVS GWLQSLEPFW VADLAFSTTL
LGQFLEDMEA YAEDLSHVAS GESVDEDVPP PSVSLPKLAA LLRVFSTVVR SIGERFSPIR
GPPITEAYVT DVLYRVMRCV TAANQVFFSE AVLTAANECV GVLLGSLDPS MTIHCDMVIT
YGLDQLENCQ TCGTDYIISV LNLLTLIVEQ INTKLPSSFV EKLFIPSSKL LFLRYHKEKE
VVAVAHAVYQ AVLSLKNIPV LETAYKLILG EMTCALNNLL HSLQLPEACS EIKHEAFKNH
VFNVDNAKFV VIFDLSALTT IGNAKNSLIG MWALSPTVFA LLSKNLMIVH SDLAVHFPAI
QYAVLYTLYS HCTRHDHFIS SSLSSSSPSL FDGAVISTVT TATKKHFSII LNLLGILLKK
DNLNQDTRKL LMTWALEAAV LMKKSETYAP LFSLPSFHKF CKGLLANTLV EDVNICLQAC
SSLHALSSSL PDDLLQRCVD VCRVQLVHSG TRIRQAFGKL LKSIPLDVVL SNNNHTEIQE
ISLALRSHMS KAPSNTFHPQ DFSDVISFIL YGNSHRTGKD NWLERLFYSC QRLDKRDQST
IPRNLLKTDA VLWQWAIWEA AQFTVLSKLR TPLGRAQDTF QTIEGIIRSL AAHTLNPDQD
VSQWTTADND EGHGNNQLRL VLLLQYLENL EKLMYNAYEG CANALTSPPK VIRTFFYTNR
QTCQDWLTRI RLSIMRVGLL AGQPAVTVRH GFDLLTEMKT TSLSQGNELE VTIMMVVEAL
CELHCPEAIQ GIAVWSSSIV GKNLLWINSV AQQAEGRFEK ASVEYQEHLC AMTGVDCCIS
SFDKSVLTLA NAGRNSASPK HSLNGESRKT VLSKPTDSSP EVINYLGNKA CECYISIADW
AAVQEWQNAI HDLKKSTSST SLNLKADFNY IKSLSSFESG KFVECTEQLE LLPGENINLL
AGGSKEKIDM KKLLPNMLSP DPRELQKSIE VQLLRSSVCL ATALNPIEQD QKWQSITENV
VKYLKQTSRI AIGPLRLSTL TVSQSLPVLS TLQLYCSSAL ENTVSNRLST EDCLIPLFSE
ALRSCKQHDV RPWMQALRYT MYQNQLLEKI KEQTVPIRSH LMELGLTAAK FARKRGNVSL
ATRLLAQCSE VQLGKTTTAQ DLVQHFKKLS TQGQVDEKWG PELDIEKTKL LYTAGQSTHA
MEMLSSCAIS FCKSVKAEYA VAKSILTLAK WIQAEWKEIS GQLKQVYRAQ HQQNFTGLST
LSKNILTLIE LPSVNTMEEE YPRIESESTV HIGVGEPDFI LGQLYHLSSV QAPEVAKSWA
ALASWAYRWG RKVVDNASQG EGVRLLPREK SEVQNLLPDT ITEEEKERIY GILGQAVCRP
AGIQDEDITL QITESEDNEE DDMVDVIWRQ LISSCPWLSE LDESATEGVI KVWRKVVDRI
FSLYKLSCSA YFTFLKLNAG QIPLDEDDPR LHLSHRVEQS TDDMIVMATL RLLRLLVKHA
GELRQYLEHG LETTPTAPWR GIIPQLFSRL NHPEVYVRQS ICNLLCRVAQ DSPHLILYPA
IVGTISLSSE SQASGNKFST AIPTLLGNIQ GEELLVSECE GGSPPASQDS NKDEPKSGLN
EDQAMMQDCY SKIVDKLSSA NPTMVLQVQM LVAELRRVTV LWDELWLGVL LQQHMYVLRR
IQQLEDEVKR VQNNNTLRKE EKIAIMREKH TALMKPIVFA LEHVRSITAA PAETPHEKWF
QDNYGDAIEN ALEKLKTPLN PAKPGSSWIP FKEIMLSLQQ RAQKRASYIL RLEEISPWLA
AMTNTEIALP GEVSARDTVT IHSVGGTITI LPTKTKPKKL LFLGSDGKSY PYLFKGLEDL
HLDERIMQFL SIVNTMFATI NRQETPRFHA RHYSVTPLGT RSGLIQWVDG ATPLFGLYKR
WQQREAALQA QKAQDSYQTP QNPGIVPRPS ELYYSKIGPA LKTVGLSLDV SRRDWPLHVM
KAVLEELMEA TPPNLLAKEL WSSCTTPDEW WRVTQSYARS TAVMSMVGYI IGLGDRHLDN
VLIDMTTGEV VHIDYNVCFE KGKSLRVPEK VPFRMTQNIE TALGVTGVEG VFRLSCEQVL
HIMRRGRETL LTLLEAFVYD PLVDWTAGGE AGFAGAVYGG GGQQAESKQS KREMEREITR
SLFSSRVAEI KVNWFKNRDE MLVVLPKLDG SLDEYLSLQE QLTDVEKLQG KLLEEIEFLE
GAEGVDHPSH TLQHRYSEHT QLQTQQRAVQ EAIQVKLNEF EQWITHYQAA FNNLEATQLA
SLLQEISTQM DLGPPSYVPA TAFLQNAGQA HLISQCEQLE GEVGALLQQR RSVLRGCLEQ
LHHYATVALQ YPKAIFQKHR IEQWKTWMEE LICNTTVERC QELYRKYEMQ YAPQPPPTVC
QFITATEMTL QRYAADINSR LIRQVERLKQ EAVTVPVCED QLKEIERCIK VFLHENGEEG
SLSLASVIIS ALCTLTRRNL MMEGAASSAG EQLVDLTSRD GAWFLEELCS MSGNVTCLVQ
LLKQCHLVPQ DLDIPNPMEA SETVHLANGV YTSLQELNSN FRQIIFPEAL RCLMKGEYTL
ESMLHELDGL IEQTTDGVPL QTLVESLQAY LRNAAMGLEE ETHAHYIDVA RLLHAQYGEL
IQPRNGSVDE TPKMSAGQML LVAFDGMFAQ VETAFSLLVE KLNKMEIPIA WRKIDIIREA
RSTQVNFFDD DNHRQVLEEI FFLKRLQTIK EFFRLCGTFS KTLSGSSSLE DQNTVNGPVQ
IVNVKTLFRN SCFSEDQMAK PIKAFTADFV RQLLIGLPNQ ALGLTLCSFI SALGVDIIAQ
VEAKDFGAES KVSVDDLCKK AVEHNIQIGK FSQLVMNRAT VLASSYDTAW KKHDLVRRLE
TSISSCKTSL QRVQLHIAMF QWQHEDLLIN RPQAMSVTPP PRSAILTSMK KKLHTLSQIE
TSIATVQEKL AALESSIEQR LKWAGGANPA LAPVLQDFEA TIAERRNLVL KESQRASQVT
FLCSNIIHFE SLRTRTAEAL NLDAALFELI KRCQQMCSFA SQFNSSVSEL ELRLLQRVDT
GLEHPIGSSE WLLSAHKQLT QDMSTQRAIQ TEKEQQIETV CETIQNLVDN IKTVLTGHNR
QLGDVKHLLK AMAKDEEAAL ADGEDVPYEN SVRQFLGEYK SWQDNIQTVL FTLVQAMGQV
RSQEHVEMLQ EITPTLKELK TQSQSIYNNL VSFASPLVTD ATNECSSPTS SATYQPSFAA
AVRSNTGQKT QPDVMSQNAR KLIQKNLATS ADTPPSTVPG TGKSVACSPK KAVRDPKTGK
AVQERNSYAV SVWKRVKAKL EGRDVDPNRR MSVAEQVDYV IKEATNLDNL AQLYEGWTAW
V
