ID   IKKE_HUMAN              Reviewed;         716 AA.
AC   Q14164; D3DT78; Q3B754; Q3KR43; Q5JTS6;
DT   20-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   06-FEB-2013, entry version 134.
DE   RecName: Full=Inhibitor of nuclear factor kappa-B kinase subunit epsilon;
DE            Short=I-kappa-B kinase epsilon;
DE            Short=IKK-E;
DE            Short=IKK-epsilon;
DE            Short=IkBKE;
DE            EC=2.7.11.10;
DE   AltName: Full=Inducible I kappa-B kinase;
DE            Short=IKK-i;
GN   Name=IKBKE; Synonyms=IKKE, IKKI, KIAA0151;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND MUTAGENESIS OF LYS-38;
RP   GLU-168 AND SER-172.
RX   MEDLINE=99352266; PubMed=10421793; DOI=10.1093/intimm/11.8.1357;
RA   Shimada T., Kawai T., Takeda K., Matsumoto M., Inoue J., Tatsumi Y.,
RA   Kanamaru A., Akira S.;
RT   "IKK-i, a novel lipopolysaccharide-inducible kinase that is related to
RT   IkappaB kinases.";
RL   Int. Immunol. 11:1357-1362(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Leukocyte;
RX   MEDLINE=20337984; PubMed=10882136; DOI=10.1016/S1097-2765(00)80445-1;
RA   Peters R.T., Liao S.-M., Maniatis T.;
RT   "IKK epsilon is part of a novel PMA-inducible IkappaB kinase
RT   complex.";
RL   Mol. Cell 5:513-522(2000).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Bone marrow;
RX   MEDLINE=96127530; PubMed=8590280; DOI=10.1093/dnares/2.4.167;
RA   Nagase T., Seki N., Tanaka A., Ishikawa K., Nomura N.;
RT   "Prediction of the coding sequences of unidentified human genes. IV.
RT   The coding sequences of 40 new genes (KIAA0121-KIAA0160) deduced by
RT   analysis of cDNA clones from human cell line KG-1.";
RL   DNA Res. 2:167-174(1995).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS LYS-128; THR-371;
RP   ASP-515; MET-543; VAL-602 AND LEU-713.
RG   SeattleSNPs variation discovery resource;
RL   Submitted (OCT-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16710414; DOI=10.1038/nature04727;
RA   Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA   Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA   Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA   McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA   Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA   Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA   Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA   Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA   Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA   Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA   Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA   Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA   Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA   Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA   Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA   Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA   Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA   Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA   Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA   Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA   Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA   Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA   Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA   Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA   Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA   Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA   Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA   Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA   Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA   Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA   Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA   Beck S., Rogers J., Bentley D.R.;
RT   "The DNA sequence and biological annotation of human chromosome 1.";
RL   Nature 441:315-321(2006).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [8]
RP   INTERACTION WITH AZI2.
RX   MEDLINE=22921922; PubMed=14560022;
RX   DOI=10.1128/MCB.23.21.7780-7793.2003;
RA   Fujita F., Taniguchi Y., Kato T., Narita Y., Furuya A., Ogawa T.,
RA   Sakurai H., Joh T., Itoh M., Delhase M., Karin M., Nakanishi M.;
RT   "Identification of NAP1, a regulatory subunit of IkappaB kinase-
RT   related kinases that potentiates NF-kappaB signaling.";
RL   Mol. Cell. Biol. 23:7780-7793(2003).
RN   [9]
RP   INTERACTION WITH TICAM1.
RX   PubMed=14739303; DOI=10.1074/jbc.M311629200;
RA   Han K.J., Su X., Xu L.-G., Bin L.H., Zhang J., Shu H.-B.;
RT   "Mechanisms of the TRIF-induced interferon-stimulated response element
RT   and NF-kappaB activation and apoptosis pathways.";
RL   J. Biol. Chem. 279:15652-15661(2004).
RN   [10]
RP   INTERACTION WITH SIKE1; IRF3; TICAM1 AND DDX58.
RX   PubMed=16281057; DOI=10.1038/sj.emboj.7600863;
RA   Huang J., Liu T., Xu L.-G., Chen D., Zhai Z., Shu H.-B.;
RT   "SIKE is an IKK epsilon/TBK1-associated suppressor of TLR3- and virus-
RT   triggered IRF-3 activation pathways.";
RL   EMBO J. 24:4018-4028(2005).
RN   [11]
RP   INTERACTION WITH MAVS.
RX   PubMed=16177806; DOI=10.1038/nature04193;
RA   Meylan E., Curran J., Hofmann K., Moradpour D., Binder M.,
RA   Bartenschlager R., Tschopp J.;
RT   "Cardif is an adaptor protein in the RIG-I antiviral pathway and is
RT   targeted by hepatitis C virus.";
RL   Nature 437:1167-1172(2005).
RN   [12]
RP   INTERACTION WITH CYLD.
RX   PubMed=18636086; DOI=10.1038/embor.2008.136;
RA   Friedman C.S., O'Donnell M.A., Legarda-Addison D., Ng A.,
RA   Cardenas W.B., Yount J.S., Moran T.M., Basler C.F., Komuro A.,
RA   Horvath C.M., Xavier R., Ting A.T.;
RT   "The tumour suppressor CYLD is a negative regulator of RIG-I-mediated
RT   antiviral response.";
RL   EMBO Rep. 9:930-936(2008).
RN   [13]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-664 AND SER-673, AND
RP   MASS SPECTROMETRY.
RX   PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
RA   Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA   Mann M., Daub H.;
RT   "Large-scale proteomics analysis of the human kinome.";
RL   Mol. Cell. Proteomics 8:1751-1764(2009).
RN   [14]
RP   FUNCTION, INTERACTION WITH TOPORS, SUMOYLATION AT LYS-231 BY TOPORS,
RP   DESUMOYLATION BY SENP1, MUTAGENESIS OF LYS-231, AND SUBCELLULAR
RP   LOCATION.
RX   PubMed=20188669; DOI=10.1016/j.molcel.2010.01.018;
RA   Renner F., Moreno R., Schmitz M.L.;
RT   "SUMOylation-dependent localization of IKKepsilon in PML nuclear
RT   bodies is essential for protection against DNA-damage-triggered cell
RT   death.";
RL   Mol. Cell 37:503-515(2010).
RN   [15]
RP   FUNCTION, AND PHOSPHORYLATION BY IKBKB/IKKB.
RX   PubMed=21138416; DOI=10.1042/BJ20101701;
RA   Clark K., Peggie M., Plater L., Sorcek R.J., Young E.R., Madwed J.B.,
RA   Hough J., McIver E.G., Cohen P.;
RT   "Novel cross-talk within the IKK family controls innate immunity.";
RL   Biochem. J. 434:93-104(2011).
RN   [16]
RP   VARIANTS [LARGE SCALE ANALYSIS] THR-371; MET-483; VAL-602; GLU-660 AND
RP   LEU-713.
RX   PubMed=17344846; DOI=10.1038/nature05610;
RA   Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C.,
RA   Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S.,
RA   O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S.,
RA   Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E.,
RA   Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J.,
RA   Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K.,
RA   Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T.,
RA   West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P.,
RA   Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E.,
RA   DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E.,
RA   Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T.,
RA   Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.;
RT   "Patterns of somatic mutation in human cancer genomes.";
RL   Nature 446:153-158(2007).
CC   -!- FUNCTION: Phosphorylates inhibitors of NF-kappa-B thus leading to
CC       the dissociation of the inhibitor/NF-kappa-B complex and
CC       ultimately the degradation of the inhibitor. May play a special
CC       role in the immune response. Protects cells against DNA damage-
CC       induced cell death.
CC   -!- CATALYTIC ACTIVITY: ATP + [I-kappa-B protein] = ADP + [I-kappa-B
CC       phosphoprotein].
CC   -!- SUBUNIT: May interact with MAVS/IPS1. Interacts with AZI2.
CC       Interacts with SIKE1. Interacts with TICAM1/TRIF, IRF3 and
CC       DDX58/RIG-I, interactions are disrupted by the interaction between
CC       IKBKE and SIKE1. Interacts with TOPORS; induced by DNA damage.
CC       Interacts with CYLD.
CC   -!- INTERACTION:
CC       Q7Z434:MAVS; NbExp=2; IntAct=EBI-307369, EBI-995373;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Nucleus, PML body.
CC       Note=Targeting to PML nuclear bodies upon DNA damage is TOPORS-
CC       dependent.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q14164-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q14164-2; Sequence=VSP_044305;
CC   -!- TISSUE SPECIFICITY: Highly expressed in spleen followed by thymus,
CC       peripheral blood leukocytes, pancreas, placenta. Weakly expressed
CC       in lung, kidney, prostate, ovary and colon.
CC   -!- PTM: Autophosphorylated and phosphorylated by IKBKB/IKKB.
CC   -!- PTM: Sumoylation by TOPORS upon DNA damage is required for
CC       protection of cells against DNA damage-induced cell death.
CC       Desumoylated by SENP1.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr
CC       protein kinase family. I-kappa-B kinase subfamily.
CC   -!- SIMILARITY: Contains 1 protein kinase domain.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAA09772.2; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC   -!- WEB RESOURCE: Name=SeattleSNPs;
CC       URL="http://pga.gs.washington.edu/data/ikbke/";
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DR   EMBL; D63485; BAA09772.2; ALT_INIT; mRNA.
DR   EMBL; AB016590; BAA85155.1; -; mRNA.
DR   EMBL; AF241789; AAF45307.1; -; mRNA.
DR   EMBL; DQ667176; ABG25921.1; -; Genomic_DNA.
DR   EMBL; AL354681; CAI15250.1; -; Genomic_DNA.
DR   EMBL; CH471100; EAW93549.1; -; Genomic_DNA.
DR   EMBL; BC105923; AAI05924.1; -; mRNA.
DR   EMBL; BC105924; AAI05925.1; -; mRNA.
DR   EMBL; BC107812; AAI07813.1; -; mRNA.
DR   IPI; IPI00029045; -.
DR   RefSeq; NP_001180250.1; NM_001193321.1.
DR   RefSeq; NP_001180251.1; NM_001193322.1.
DR   RefSeq; NP_054721.1; NM_014002.3.
DR   UniGene; Hs.321045; -.
DR   ProteinModelPortal; Q14164; -.
DR   SMR; Q14164; 2-383.
DR   DIP; DIP-27530N; -.
DR   IntAct; Q14164; 8.
DR   MINT; MINT-1132084; -.
DR   STRING; Q14164; -.
DR   PhosphoSite; Q14164; -.
DR   DMDM; 14548079; -.
DR   PRIDE; Q14164; -.
DR   DNASU; 9641; -.
DR   Ensembl; ENST00000367120; ENSP00000356087; ENSG00000143466.
DR   Ensembl; ENST00000537984; ENSP00000444529; ENSG00000143466.
DR   Ensembl; ENST00000581977; ENSP00000464030; ENSG00000263528.
DR   Ensembl; ENST00000584998; ENSP00000462396; ENSG00000263528.
DR   GeneID; 9641; -.
DR   KEGG; hsa:9641; -.
DR   UCSC; uc001hdz.2; human.
DR   CTD; 9641; -.
DR   GeneCards; GC01P206643; -.
DR   H-InvDB; HIX0116011; -.
DR   HGNC; HGNC:14552; IKBKE.
DR   HPA; CAB025983; -.
DR   HPA; HPA015788; -.
DR   MIM; 605048; gene.
DR   neXtProt; NX_Q14164; -.
DR   PharmGKB; PA134962294; -.
DR   eggNOG; COG0515; -.
DR   HOGENOM; HOG000220867; -.
DR   HOVERGEN; HBG008494; -.
DR   InParanoid; Q14164; -.
DR   KO; K07211; -.
DR   OMA; KNRDQVH; -.
DR   OrthoDB; EOG4S4PFW; -.
DR   PhylomeDB; Q14164; -.
DR   BRENDA; 2.7.11.10; 2681.
DR   Reactome; REACT_6900; Immune System.
DR   ChEMBL; CHEMBL3529; -.
DR   GenomeRNAi; 9641; -.
DR   NextBio; 36191; -.
DR   ArrayExpress; Q14164; -.
DR   Bgee; Q14164; -.
DR   CleanEx; HS_IKBKE; -.
DR   Genevestigator; Q14164; -.
DR   GermOnline; ENSG00000143466; Homo sapiens.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0010008; C:endosome membrane; TAS:Reactome.
DR   GO; GO:0016605; C:PML body; IDA:UniProtKB.
DR   GO; GO:0005524; F:ATP binding; NAS:UniProtKB.
DR   GO; GO:0008384; F:IkappaB kinase activity; IEA:EC.
DR   GO; GO:0004704; F:NF-kappaB-inducing kinase activity; IDA:UniProtKB.
DR   GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR   GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IMP:UniProtKB.
DR   GO; GO:0032480; P:negative regulation of type I interferon production; TAS:Reactome.
DR   GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB cascade; IEP:UniProtKB.
DR   GO; GO:0008063; P:Toll signaling pathway; TAS:Reactome.
DR   GO; GO:0034138; P:toll-like receptor 3 signaling pathway; TAS:Reactome.
DR   GO; GO:0034142; P:toll-like receptor 4 signaling pathway; TAS:Reactome.
DR   GO; GO:0035666; P:TRIF-dependent toll-like receptor signaling pathway; TAS:Reactome.
DR   InterPro; IPR011009; Kinase-like_dom.
DR   InterPro; IPR000719; Prot_kinase_cat_dom.
DR   InterPro; IPR017441; Protein_kinase_ATP_BS.
DR   Pfam; PF00069; Pkinase; 1.
DR   SUPFAM; SSF56112; Kinase_like; 1.
DR   PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   PROSITE; PS00108; PROTEIN_KINASE_ST; FALSE_NEG.
PE   1: Evidence at protein level;
KW   Alternative splicing; ATP-binding; Complete proteome; Cytoplasm;
KW   DNA damage; Isopeptide bond; Kinase; Nucleotide-binding; Nucleus;
KW   Phosphoprotein; Polymorphism; Reference proteome;
KW   Serine/threonine-protein kinase; Transferase; Ubl conjugation.
FT   CHAIN         1    716       Inhibitor of nuclear factor kappa-B
FT                                kinase subunit epsilon.
FT                                /FTId=PRO_0000086017.
FT   DOMAIN        9    315       Protein kinase.
FT   NP_BIND      15     23       ATP (By similarity).
FT   REGION      436    457       Leucine-zipper.
FT   ACT_SITE    135    135       Proton acceptor (By similarity).
FT   BINDING      38     38       ATP (By similarity).
FT   MOD_RES     172    172       Phosphoserine; by IKKB.
FT   MOD_RES     664    664       Phosphoserine.
FT   MOD_RES     673    673       Phosphoserine.
FT   CROSSLNK    231    231       Glycyl lysine isopeptide (Lys-Gly)
FT                                (interchain with G-Cter in SUMO1).
FT   VAR_SEQ       1     85       Missing (in isoform 2).
FT                                /FTId=VSP_044305.
FT   VARIANT     128    128       E -> K (in dbSNP:rs41296028).
FT                                /FTId=VAR_038816.
FT   VARIANT     371    371       A -> T (in dbSNP:rs17021877).
FT                                /FTId=VAR_038817.
FT   VARIANT     483    483       T -> M (in dbSNP:rs52817862).
FT                                /FTId=VAR_040571.
FT   VARIANT     515    515       E -> D (in dbSNP:rs41299015).
FT                                /FTId=VAR_038818.
FT   VARIANT     543    543       I -> M (in dbSNP:rs41299037).
FT                                /FTId=VAR_038819.
FT   VARIANT     602    602       A -> V (in dbSNP:rs12059562).
FT                                /FTId=VAR_038820.
FT   VARIANT     660    660       G -> E (in dbSNP:rs55822317).
FT                                /FTId=VAR_040572.
FT   VARIANT     713    713       P -> L (in dbSNP:rs3748022).
FT                                /FTId=VAR_019989.
FT   MUTAGEN      38     38       K->A: Loss of kinase activity and loss of
FT                                nuclear import.
FT   MUTAGEN     168    168       E->A: Slight decrease of kinase activity.
FT   MUTAGEN     172    172       S->A: Loss of autophosphorylation and of
FT                                kinase activity.
FT   MUTAGEN     172    172       S->E: Decrease in kinase activity.
FT   MUTAGEN     231    231       K->R: Loss of sumoylation and loss of
FT                                targeting to nuclear bodies.
FT   CONFLICT    187    187       R -> Q (in Ref. 7; AAI05925).
SQ   SEQUENCE   716 AA;  80462 MW;  3E5FBE5840734D81 CRC64;
     MQSTANYLWH TDDLLGQGAT ASVYKARNKK SGELVAVKVF NTTSYLRPRE VQVREFEVLR
     KLNHQNIVKL FAVEETGGSR QKVLVMEYCS SGSLLSVLES PENAFGLPED EFLVVLRCVV
     AGMNHLRENG IVHRDIKPGN IMRLVGEEGQ SIYKLTDFGA ARELDDDEKF VSVYGTEEYL
     HPDMYERAVL RKPQQKAFGV TVDLWSIGVT LYHAATGSLP FIPFGGPRRN KEIMYRITTE
     KPAGAIAGAQ RRENGPLEWS YTLPITCQLS LGLQSQLVPI LANILEVEQA KCWGFDQFFA
     ETSDILQRVV VHVFSLSQAV LHHIYIHAHN TIAIFQEAVH KQTSVAPRHQ EYLFEGHLCV
     LEPSVSAQHI AHTTASSPLT LFSTAIPKGL AFRDPALDVP KFVPKVDLQA DYNTAKGVLG
     AGYQALRLAR ALLDGQELMF RGLHWVMEVL QATCRRTLEV ARTSLLYLSS SLGTERFSSV
     AGTPEIQELK AAAELRSRLR TLAEVLSRCS QNITETQESL SSLNRELVKS RDQVHEDRSI
     QQIQCCLDKM NFIYKQFKKS RMRPGLGYNE EQIHKLDKVN FSHLAKRLLQ VFQEECVQKY
     QASLVTHGKR MRVVHETRNH LRLVGCSVAA CNTEAQGVQE SLSKLLEELS HQLLQDRAKG
     AQASPPPIAP YPSPTRKDLL LHMQELCEGM KLLASDLLDN NRIIERLNRV PAPPDV
//