PUF_DROME
ID PUF_DROME Reviewed; 3912 AA.
AC Q9VC56; Q7KS15;
DT 25-OCT-2017, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 2.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase puf {ECO:0000305};
DE EC=3.4.19.12 {ECO:0000250|UniProtKB:Q70CQ2};
DE AltName: Full=Protein puffyeye {ECO:0000303|PubMed:24173801};
GN Name=puf {ECO:0000303|PubMed:24173801, ECO:0000312|FlyBase:FBgn0039214};
GN Synonyms=Usp34 {ECO:0000303|PubMed:25027767};
GN ORFNames=CG5794 {ECO:0000312|FlyBase:FBgn0039214};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227 {ECO:0000312|Proteomes:UP000000803};
RN [1] {ECO:0000312|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2] {ECO:0000312|Proteomes:UP000000803}
RP GENOME REANNOTATION.
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3] {ECO:0000305}
RP FUNCTION, INTERACTION WITH MYC AND AGO, SUBCELLULAR LOCATION, DISRUPTION
RP PHENOTYPE, AND MUTAGENESIS OF CYS-2024; HIS-2305 AND ASN-2328.
RX PubMed=24173801; DOI=10.1242/dev.096941;
RA Li L., Anderson S., Secombe J., Eisenman R.N.;
RT "The Drosophila ubiquitin-specific protease Puffyeye regulates dMyc-
RT mediated growth.";
RL Development 140:4776-4787(2013).
RN [4] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=25027767; DOI=10.1186/s12964-014-0041-2;
RA Engel E., Viargues P., Mortier M., Taillebourg E., Coute Y., Thevenon D.,
RA Fauvarque M.O.;
RT "Identifying USPs regulating immune signals in Drosophila: USP2
RT deubiquitinates Imd and promotes its degradation by interacting with the
RT proteasome.";
RL Cell Commun. Signal. 12:41-41(2014).
CC -!- FUNCTION: Ubiquitin hydrolase that can remove conjugated ubiquitin from
CC target proteins and polyubiquitin chains (PubMed:24173801). Essential
CC for Myc-mediated cell growth and proliferation in developing eyes and
CC wings (PubMed:24173801). In the wing and eye, the deubiquitinating
CC activity acts as an antagonist to the SCF E3 ubiquitin-protein ligase
CC member archipelago (ago) to regulate Myc and CycE stability and thus
CC control cell growth and proliferation (PubMed:24173801). Also appears
CC to regulate ago by modulating its induction by Myc (PubMed:24173801).
CC May also promote cell apoptosis in the wing imaginal disk, acting in an
CC apoptotic pathway that appears to be largely independent of Myc
CC (PubMed:24173801). Required for preventing the activation of the immune
CC deficiency (Imd) and Toll signaling cascades under unchallenged
CC conditions (PubMed:25027767). Also appears to be involved in modulating
CC the differential expression of certain antimicrobial peptides (AMP) in
CC response to infection by either Gram-positive or Gram-negative bacteria
CC (PubMed:25027767). {ECO:0000269|PubMed:24173801,
CC ECO:0000269|PubMed:25027767}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide
CC and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-
CC residue protein attached to proteins as an intracellular targeting
CC signal).; EC=3.4.19.12; Evidence={ECO:0000250|UniProtKB:Q70CQ2};
CC -!- SUBUNIT: Interacts with Myc and ago. {ECO:0000269|PubMed:24173801}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:24173801}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=D {ECO:0000312|FlyBase:FBgn0039214}; Synonyms=long
CC {ECO:0000303|PubMed:24173801};
CC IsoId=Q9VC56-1; Sequence=Displayed;
CC Name=2 {ECO:0000312|FlyBase:FBgn0039214}; Synonyms=short
CC {ECO:0000303|PubMed:24173801};
CC IsoId=Q9VC56-2; Sequence=VSP_059118, VSP_059119;
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown is pupal lethal
CC (PubMed:24173801). RNAi-mediated knockdown in the dorsal part of the
CC larval wing disk results in adult wings displaying an upward curvature
CC possibly due to cells on the dorsal side being relatively smaller than
CC cells on the ventral side (PubMed:24173801). RNAi-mediated knockdown in
CC the fat body results in the activation of the Imd and Toll signaling
CC pathways under unchallenged conditions, with constitutive expression of
CC Toll (Drs, IM1) and Imd (DptA, Def, Atta) antimicrobial peptides
CC (PubMed:25027767). Flies infected with E.coli display enhanced
CC expression of Atta compared to controls, whereas expression levels of
CC DptA and Def are decreased (PubMed:25027767). Flies infected with
CC M.luteus display increased expression of Drs, IM1 and also Atta 3 h
CC after infection, whereas 24 h after infection increased expression is
CC only maintained in Atta and IM1 (PubMed:25027767). Double knockdown
CC with imd prevents the enhanced expression of Atta and DptA in
CC uninfected and infected flies (PubMed:25027767).
CC {ECO:0000269|PubMed:24173801, ECO:0000269|PubMed:25027767}.
CC -!- MISCELLANEOUS: The name 'Puffyeye' derives from its role in regulating
CC the Myc-dependent rough eye phenotype. {ECO:0000303|PubMed:24173801}.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. {ECO:0000255|PROSITE-
CC ProRule:PRU01035}.
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DR EMBL; AE014297; AAF56319.2; -; Genomic_DNA.
DR EMBL; AE014297; AAS65209.1; -; Genomic_DNA.
DR RefSeq; NP_651275.1; NM_143018.4. [Q9VC56-1]
DR RefSeq; NP_996287.1; NM_206564.2. [Q9VC56-2]
DR SMR; Q9VC56; -.
DR IntAct; Q9VC56; 4.
DR STRING; 7227.FBpp0303340; -.
DR MEROPS; C19.A46; -.
DR EnsemblMetazoa; FBtr0084667; FBpp0084047; FBgn0039214. [Q9VC56-2]
DR EnsemblMetazoa; FBtr0084668; FBpp0084048; FBgn0039214. [Q9VC56-1]
DR GeneID; 42935; -.
DR KEGG; dme:Dmel_CG5794; -.
DR UCSC; CG5794-RB; d. melanogaster. [Q9VC56-1]
DR CTD; 42935; -.
DR FlyBase; FBgn0039214; puf.
DR VEuPathDB; VectorBase:FBgn0039214; -.
DR eggNOG; KOG1866; Eukaryota.
DR HOGENOM; CLU_000109_0_0_1; -.
DR InParanoid; Q9VC56; -.
DR OMA; TIEXIRI; -.
DR PhylomeDB; Q9VC56; -.
DR Reactome; R-DME-201681; TCF dependent signaling in response to WNT.
DR Reactome; R-DME-5689880; Ub-specific processing proteases.
DR SignaLink; Q9VC56; -.
DR BioGRID-ORCS; 42935; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 42935; -.
DR PRO; PR:Q9VC56; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0039214; Expressed in cleaving embryo and 23 other tissues.
DR ExpressionAtlas; Q9VC56; baseline and differential.
DR Genevisible; Q9VC56; DM.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IDA:FlyBase.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; ISS:FlyBase.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0002785; P:negative regulation of antimicrobial peptide production; IMP:FlyBase.
DR GO; GO:0045824; P:negative regulation of innate immune response; IMP:FlyBase.
DR GO; GO:0061060; P:negative regulation of peptidoglycan recognition protein signaling pathway; IMP:FlyBase.
DR GO; GO:0045751; P:negative regulation of Toll signaling pathway; IMP:FlyBase.
DR GO; GO:0030307; P:positive regulation of cell growth; IMP:FlyBase.
DR GO; GO:0043687; P:post-translational protein modification; IMP:FlyBase.
DR GO; GO:0016579; P:protein deubiquitination; IMP:FlyBase.
DR GO; GO:0031647; P:regulation of protein stability; IMP:FlyBase.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR GO; GO:0035220; P:wing disc development; IMP:FlyBase.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR021905; DUF3517.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR001394; Peptidase_C19_UCH.
DR InterPro; IPR018200; USP_CS.
DR InterPro; IPR028889; USP_dom.
DR Pfam; PF12030; DUF3517; 1.
DR Pfam; PF00443; UCH; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS00972; USP_1; 1.
DR PROSITE; PS00973; USP_2; 1.
DR PROSITE; PS50235; USP_3; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Hydrolase; Nucleus; Protease; Reference proteome;
KW Thiol protease; Ubl conjugation pathway.
FT CHAIN 1..3912
FT /note="Ubiquitin carboxyl-terminal hydrolase puf"
FT /id="PRO_0000441820"
FT DOMAIN 2015..2380
FT /note="USP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01035"
FT REGION 101..172
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 518..590
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 660..688
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 851..878
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1491..1611
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2249..2274
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2391..2529
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3322..3344
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3657..3776
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3800..3912
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 110..136
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 152..166
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 567..590
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 660..683
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 858..878
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1491..1511
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1549..1571
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1572..1592
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2403..2493
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2494..2529
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3657..3701
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3702..3734
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3750..3776
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3863..3890
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3897..3912
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 2024
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01035,
FT ECO:0000305|PubMed:24173801"
FT ACT_SITE 2305
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01035,
FT ECO:0000305|PubMed:24173801"
FT VAR_SEQ 2824..2832
FT /note="GFPFLYQQI -> VILKKLESF (in isoform 2)"
FT /id="VSP_059118"
FT VAR_SEQ 2833..3912
FT /note="Missing (in isoform 2)"
FT /id="VSP_059119"
FT MUTAGEN 2024
FT /note="C->A: Loss of activity in Myc-mediated growth in the
FT wing and eye, and no increase in the expression of CycE in
FT the wing imaginal disk when overexpressed. Unable to
FT increase expression of Myc and ago in the wing imaginal
FT disk when overexpressed; when associated with A-2305 and A-
FT 2328."
FT /evidence="ECO:0000269|PubMed:24173801"
FT MUTAGEN 2305
FT /note="H->A: Loss of activity in Myc-mediated growth in the
FT wing and eye, and unable to increase expression of Myc and
FT ago in the wing imaginal disk when overexpressed; when
FT associated with A-2024 and A-2328."
FT /evidence="ECO:0000269|PubMed:24173801"
FT MUTAGEN 2328
FT /note="N->A: Loss of activity in Myc-mediated growth in the
FT wing and eye, and unable to increase expression of Myc and
FT ago in the wing imaginal disk when overexpressed; when
FT associated with A-2024 and A-2305."
FT /evidence="ECO:0000269|PubMed:24173801"
SQ SEQUENCE 3912 AA; 440375 MW; 2F2A66EDC87751D5 CRC64;
MCEVCADFQN LLELYEVRVA SSDLKFQLLL KSEIETTFNY IQSWPQRQCM CLYRDTKNYD
RFNLVVQSLI CLTVQHLKHI DHLIDNYKRL TASAAQVVAQ AQQQREQQRD EASAQAEAKE
SSAPAEEPKK EEPSGSAGEE AQGSGDGPAK KPPVGPCTPP PPQTANPQHK SHLQYTEEPW
ILPEVEKLLV LVSKVFLLNF PLYIAHKHGM HSRLDDLQAE EAHHLALICD LHDNDLPIYL
LRNVSLFCNS GGFGAMSLCF EHPDLPVSTA HSMTAAVSNV KLWLNYHCNT QLFVPLRSRI
LQYMCKLSDQ SLRSAATRAM ADFVWSSMRD PLDVAVNFDT EGLALAFKYF TSTTLTMRLA
GMAQINAHIN LFNEICTTET VNEVELFGQR IANWLTENHI VQHLFGPNLH VEIVKQAHVL
LNFLAVENQI SEEDIKLIWQ ATQLKHCSKT IFDILPSLVK NLTPRPAMHL YSLLCRMDPK
EHTEQSIYIA SALTKQLWTR DTSRSQMNLM QDHLLGSNVT ASSSDSGSIE GSNTEDDHVG
ADDSSIASGG GGGGVGNKSP IDGVTPCKQA RHRRHICDPT TEKGKQISPE DMAKVDLVNK
RIVNIIDNTS SEEELQSRAA LELQLHRSRK KTSNKRRRQK TNKQIILPHE LVEIWDGVED
VPSSDEADGE ADGDGEGELL ADSDECSDGA TSQLVPDAVL KHLQGEGPFI RAIETNINEL
LSGAENDGSY SSPMSNKSEK NLADFDDEDV SPCEEELAQL VSSRANCSDV PPAFAAAAAA
MMVAQSAMAL QKSGESNVAA AAAAVAAAAA ATGTAQQTLV AMNRQASVAA AAAVVAAAKA
KSDSDVDLMD VVSGGKQHHS PKASQGSSTS GSTPVQPSFK LNDVCQPGNT LLWDLLQDDK
IGQLGESLAL EAEKALATLL CFSMDRQLRT KFIEGCLYNV ANNRSVIVSL RLLPKLFASF
QQFRPSDTHS MTMWAERNHR MMQCFFNNIR HYARRHAEVL ITQNGEQQQQ QLGGQLYSHK
TQVSVRLQFL SSIFSTVGSP KSFRLTLEQL DALWEWLAHD PECADCYFSW LQAQAKGGDQ
HALGIEALQH LYLKKLPELR PEEFSMVALG LFQQLCSFAR IAMAEYDNHS DQISASASAV
GMYHLWKIAL RAQSNDVSLA AIQYINMYYM GQQLRLEKEF VSQCMENLVQ AATALESIDD
ENALMRVQRG LLLLNTHLDT FRRRYAFHLR RWAIEGKGIG SHSNLKNEGA GPPLRIVLQQ
AGLSEKSLLQ MHACDLIADL KAEVSKWWES LQTGLAAPVL GLLLSDGPLR IITQGQELTS
DYDERSLGDA GFKDNQIVYV SLGGRGARRK ESNLEHPSML PPPPKECLPT VLLLQPKYFE
KLFCLMQTLG DMQPQASTVN PQHHTKAQLL SRRVWDILAM LPTNPHILDA FKSLVTDLSE
LEQLDAGGEE EQLATKRKQI KQKFRDLLDP NNLQKFMYSL HIVESLALTS SRRGESNGNV
AMGNTPEQVR VKKSSMGRRR NSNEQPPPPP PEVKMSKEQL CELEAPLTPT PSTGLQDVET
EASSSSGGDK ENQPKQHSKR QKKGETFEQE KERPVGCSTP PSPTPPPPAL SVVERGDNKW
SEAFVKCGGL RHLYEIFSEG QLQQSAHPKE LALNEWRHDC LASLLRILWL LGFEELQSAD
AHVLMSRPHP FMLQLMEVPQ CLTRLSSILN DEVHQQHQAS SANPLVFPYQ FQHLRTGFWG
RAQLIQFAMN ILVSFVHASA EARRLLWAPT GTDHCRWLQK FILEDPEPAV RREICAGLYR
ICLGNAHSYR LLLAPLLHKL IALLPLAEQM SSGNQHTQFL LSEEGKDPYG PACRDYFWLL
ARLVDTLSPE MVAEEHIDIE MLCESISQSI LTREYYELRH GYQDDGLVGL LNLMSNLIKY
DTTFKYTPKA LSFIEQLIGF LFDMPSPADR QKPKCKSASS RASAYDLLVE LCRGCATNYA
YLHGRLLAQH KSGPKQPYPW DYWPRDEGRA ECGYVGLTNL GATCYMASCV QHLYMMPQAR
AAVLRVPPNA ARKHGPTLLE LQRMFAYLLE SERKSYNPRS FCRVYQMDHQ PLNTGEQKDM
AEFFIDLVSK LEDMTPDLKH LVKRLFCGSL SNNVVSLDCG HVSRTAEDFY TVRCQVADMR
NLQESLDEVT VKDTLEGDNM YTCSQCGKKV RAEKRACFKK LPQILCFNTM RYTFNMVTML
KEKVNTHFSF PLRLNMCHYV EKTLMPQQYK EERERRQKEK EGADGSGDGN DNEKAEATLD
DDIEECYEYE LVGVTVHTGT ADGGHYYSFI KERTKTSYHT HERWFLFNDA EVKPFDPSQI
AAECFGGEMT SKTYDSVTEK YLDFSFEKTN SAYMLFYERR LPEHLQRRHS ELLVTPTPSP
TVEEKSEAEE PTKMETSSSE IKADVDVEVE VEEKDKEKPA QTDTESKETP AKEEIADDKS
KQDEPEEKKI EKQSREGEEK SETDEKPTEM TTVSTEEEKQ PTANCDNHQQ NNNSNSKASN
DQQPSTSKAA QKLQLFRPLL NKELEDWIWQ DNRQFLQDRN IFEHTYFNFM WQICGHIPQS
LISETDVTCM AAKLSVSFFI ETFIHAKEKP TMVPWVELLT KQFNASQEAC EWFLSHMSQE
PYWPVQVLIQ CPNQMVRQMF QRLVIHVIQQ LRASHAHLYL EVETDEDDKE LIGQASCVTR
FIGSLISLLE HGARANLRHL SEYFGLLCEF SRMGDEEAMY LLRIGVLKSL VDFYLGHKQT
DSIDISSDNE DNSSEEALSV EKMRPASLDK MIALCASLVE RSRGADFRLR LSPKDFSAIA
GGKGFPFLYQ QIKDGINPHQ TKHLIHALCR WDERLATQII GMLFASVTKH TELCAPFFKL
LTLLTETQGG PVGLPCFTQL ILPRMWDAAE YCPQSVLDWL SLQATKNKIA HAWILQSAEK
WLEQFLLAHD NTRVRNAAAF LLVALVPSQP FRANFRAHSQ HKLLALNPHS YRDINSDAQA
VLHQVITLLL RLLRPARVYA DIGAHGTTKL TAYFNLLSYC MVSKTEKLMA SSYMRSLWEL
FHPRLSEPSV PAHHNKHALL TFWHHSLVDC PENAAQVANC PEITRNIAFN YILADHDDAE
IVTYNRSMLP AYYGLLRLCC EQSRALTRQL SQHQNLQWAF KNITPHPTQY AAAVDELFKL
MALFATRHPD ASEQEKLDVT QFRRAVIVSY TSSLDARVSW STLISALKIL VDNEEDRTMV
IFNGGIEMCF EALHTLHSMH HEATACHVAG DLFDLLGEML LLLATLRTRT DSPAQKKQQQ
QQQQLEQQLQ LQQQQMLQKQ QQQSQSQTQT PQSPQQKEKQ LQQQMQQHLQ LQQLQQMQFQ
QQHFLRQQHQ HSALAKALPD AVKRLATLLN TFNSPEISRM ALEVLKELVR NPSLETISIL
APILINCHLS VANAPNAIGP LGPYFPRRGA KHTPWPLGAK NSPRPPRPMV QMCIALAELT
PRGLDADYDV QVESFYRPYH DFIDVMMRMC VNTGTLNDTL VKLQCLVAIE STPLHFTYFP
KFWVGIHNNA LTHKYVELLV KNQLLVEYLH NVLRDERSML KDACVREFLE LYYHKVAAQL
PVARMIYTIN YGMHSKDDID ELCGDLFAIR IIAQATGVPA SVRKELRGSL RALQNKSERF
RKESERDPFP NKKQKRDSQK IKEKEHPQPE SEKETSTEND KPSDVSMESS GNAEQATDST
KPPTPAGSDD EQMDKTSVPS SDDETELEDE LQPTPKRNKK ASNKKTAQDR VNEEREKRLI
TLITMESYIQ SIFAILKRDA SVPSSGATKE PSEEPCGEAS TSAAAAVKLS RPKGACTPPE
PITDVNDTRC NIDTETEAEA DEQSPKTSQT NGSQQNESPP AATSADTAPA NPSPAPAAAV
ASTSQAASPT QI
