USP9X_MOUSE
ID USP9X_MOUSE Reviewed; 2559 AA.
AC P70398; E9QLY0; Q62497;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Probable ubiquitin carboxyl-terminal hydrolase FAF-X;
DE EC=3.4.19.12 {ECO:0000269|PubMed:29626158, ECO:0000269|PubMed:30951545};
DE AltName: Full=Deubiquitinating enzyme FAF-X;
DE AltName: Full=Fat facets homolog;
DE AltName: Full=Fat facets protein-related, X-linked;
DE AltName: Full=Ubiquitin carboxyl-terminal hydrolase FAM;
DE AltName: Full=Ubiquitin thioesterase FAF-X;
DE AltName: Full=Ubiquitin-specific protease 9, X chromosome;
DE AltName: Full=Ubiquitin-specific-processing protease FAF-X;
GN Name=Usp9x {ECO:0000303|PubMed:24607389, ECO:0000312|MGI:MGI:894681};
GN Synonyms=Fafl, Fam;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=9178254; DOI=10.1016/s0925-4773(97)00672-2;
RA Wood S.A., Pascoe W.S., Ru K., Yamada T., Hirchenhain J., Kemler R.,
RA Mattick J.S.;
RT "Cloning and expression analysis of a novel mouse gene with sequence
RT similarity to the Drosophila fat facets gene.";
RL Mech. Dev. 63:29-38(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 152-240.
RC TISSUE=Cochlea;
RX PubMed=9119401; DOI=10.1006/geno.1996.4526;
RA Crozet F., El-Amraoui A., Blanchard S., Lenoir M., Ripoll C., Vago P.,
RA Hamel C., Fizames C., Levi-Acobas F., Depetris D., Mattei M.-G., Weil D.,
RA Pujol R., Petit C.;
RT "Cloning of the genes encoding two murine and human cochlear unconventional
RT type I myosins.";
RL Genomics 40:332-341(1997).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-2540, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Mast cell;
RX PubMed=17947660; DOI=10.4049/jimmunol.179.9.5864;
RA Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y.,
RA Kawakami T., Salomon A.R.;
RT "Quantitative time-resolved phosphoproteomic analysis of mast cell
RT signaling.";
RL J. Immunol. 179:5864-5876(2007).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1600, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-374; SER-375; SER-1600 AND
RP SER-2443, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP SUBCELLULAR LOCATION, FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24607389; DOI=10.1016/j.ajhg.2014.02.004;
RA Homan C.C., Kumar R., Nguyen L.S., Haan E., Raymond F.L., Abidi F.,
RA Raynaud M., Schwartz C.E., Wood S.A., Gecz J., Jolly L.A.;
RT "Mutations in USP9X are associated with X-linked intellectual disability
RT and disrupt neuronal cell migration and growth.";
RL Am. J. Hum. Genet. 94:470-478(2014).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH ARNTL.
RX PubMed=29626158; DOI=10.1042/bcj20180005;
RA Zhang Y., Duan C., Yang J., Chen S., Liu Q., Zhou L., Huang Z., Xu Y.,
RA Xu G.;
RT "Deubiquitinating enzyme USP9X regulates cellular clock function by
RT modulating the ubiquitination and degradation of a core circadian protein
RT BMAL1.";
RL Biochem. J. 475:1507-1522(2018).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, AND MUTAGENESIS OF CYS-1566.
RX PubMed=30951545; DOI=10.1371/journal.pone.0214110;
RA Abed M., Verschueren E., Budayeva H., Liu P., Kirkpatrick D.S., Reja R.,
RA Kummerfeld S.K., Webster J.D., Gierke S., Reichelt M., Anderson K.R.,
RA Newman R.J., Roose-Girma M., Modrusan Z., Pektas H., Maltepe E., Newton K.,
RA Dixit V.M.;
RT "The Gag protein PEG10 binds to RNA and regulates trophoblast stem cell
RT lineage specification.";
RL PLoS ONE 14:e0214110-e0214110(2019).
RN [10]
RP TISSUE SPECIFICITY.
RX PubMed=33378666; DOI=10.1016/j.celrep.2020.108564;
RA Wrobel L., Siddiqi F.H., Hill S.M., Son S.M., Karabiyik C., Kim H.,
RA Rubinsztein D.C.;
RT "mTORC2 Assembly Is Regulated by USP9X-Mediated Deubiquitination of
RT RICTOR.";
RL Cell Rep. 33:108564-108564(2020).
CC -!- FUNCTION: Deubiquitinase involved both in the processing of ubiquitin
CC precursors and of ubiquitinated proteins (PubMed:29626158,
CC PubMed:30951545). May therefore play an important regulatory role at
CC the level of protein turnover by preventing degradation of proteins
CC through the removal of conjugated ubiquitin (PubMed:29626158,
CC PubMed:30951545). Specifically hydrolyzes 'Lys-63'-, 'Lys-48'-, 'Lys-
CC 29'- and 'Lys-33'-linked polyubiquitins chains (By similarity).
CC Essential component of TGF-beta/BMP signaling cascade (By similarity).
CC Specifically deubiquitinates monoubiquitinated SMAD4, opposing the
CC activity of E3 ubiquitin-protein ligase TRIM33 (By similarity).
CC Deubiquitinates alkylation repair enzyme ALKBH3 (By similarity). OTUD4
CC recruits USP7 and USP9X to stabilize ALKBH3, thereby promoting the
CC repair of alkylated DNA lesions (By similarity). Deubiquitinates mTORC2
CC complex component RICTOR at 'Lys-294' by removing 'Lys-63'-linked
CC polyubiquitin chains, stabilizing RICTOR and enhancing its binding to
CC MTOR, thus promoting mTORC2 complex assembly (By similarity). Regulates
CC chromosome alignment and segregation in mitosis by regulating the
CC localization of BIRC5/survivin to mitotic centromeres (By similarity).
CC Involved in axonal growth and neuronal cell migration
CC (PubMed:24607389). Regulates cellular clock function by enhancing the
CC protein stability and transcriptional activity of the core circadian
CC protein ARNTL/BMAL1 via its deubiquitinating activity
CC (PubMed:29626158). Deubiquitinates PEG10 (PubMed:30951545).
CC {ECO:0000250|UniProtKB:Q93008, ECO:0000269|PubMed:24607389,
CC ECO:0000269|PubMed:29626158, ECO:0000269|PubMed:30951545}.
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:0000269|PubMed:29626158,
CC ECO:0000269|PubMed:30951545};
CC -!- SUBUNIT: Interacts with SMAD4, MARK4, NUAK1 and BIRC5/survivin.
CC Interacts with DCX. Interacts with OTUD4 and USP7; the interaction is
CC direct (By similarity). Interacts with ARNTL/BMAL1 (PubMed:29626158).
CC Interacts with RICTOR; the interaction results in deubiquitination of
CC RICTOR and protection from proteasomal degradation (By similarity).
CC {ECO:0000250|UniProtKB:Q93008, ECO:0000269|PubMed:29626158}.
CC -!- INTERACTION:
CC P70398; A5PKW4: PSD; Xeno; NbExp=3; IntAct=EBI-2214043, EBI-719999;
CC P70398; Q13485: SMAD4; Xeno; NbExp=4; IntAct=EBI-2214043, EBI-347263;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q93008}. Cell
CC projection, growth cone {ECO:0000269|PubMed:24607389}. Cytoplasm,
CC cytoskeleton, cilium axoneme {ECO:0000250|UniProtKB:Q93008}.
CC -!- TISSUE SPECIFICITY: Highest levels in liver and brain with expression
CC also detected in heart, muscle, spleen and kidney (at protein leve)
CC (PubMed:33378666). Ubiquitously expressed in adult tissues
CC (PubMed:9178254). {ECO:0000269|PubMed:33378666,
CC ECO:0000269|PubMed:9178254}.
CC -!- DEVELOPMENTAL STAGE: At least expressed from 17 dpc to 21 postnatal
CC days. {ECO:0000269|PubMed:9178254}.
CC -!- DISRUPTION PHENOTYPE: Brain-specific USP9X deletion results in early
CC postnatal death, whereas forebrain-specific deletion is compatible with
CC survival to adulthood. In the absence of USP9X the cortical
CC architecture is disorganized, and neurons display reduced neurite
CC growth. {ECO:0000269|PubMed:24607389}.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. {ECO:0000305}.
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DR EMBL; U67874; AAB07731.1; -; mRNA.
DR EMBL; AL669967; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z78153; CAB01555.1; -; mRNA.
DR PIR; T30850; T30850.
DR RefSeq; NP_033507.2; NM_009481.2.
DR AlphaFoldDB; P70398; -.
DR SMR; P70398; -.
DR BioGRID; 204467; 35.
DR IntAct; P70398; 16.
DR MINT; P70398; -.
DR STRING; 10090.ENSMUSP00000086716; -.
DR MEROPS; C19.017; -.
DR iPTMnet; P70398; -.
DR PhosphoSitePlus; P70398; -.
DR SwissPalm; P70398; -.
DR EPD; P70398; -.
DR jPOST; P70398; -.
DR MaxQB; P70398; -.
DR PaxDb; P70398; -.
DR PeptideAtlas; P70398; -.
DR PRIDE; P70398; -.
DR ProteomicsDB; 300203; -.
DR DNASU; 22284; -.
DR GeneID; 22284; -.
DR KEGG; mmu:22284; -.
DR CTD; 8239; -.
DR MGI; MGI:894681; Usp9x.
DR eggNOG; KOG1866; Eukaryota.
DR InParanoid; P70398; -.
DR OrthoDB; 625455at2759; -.
DR Reactome; R-MMU-2173795; Downregulation of SMAD2/3:SMAD4 transcriptional activity.
DR Reactome; R-MMU-5689880; Ub-specific processing proteases.
DR Reactome; R-MMU-8866652; Synthesis of active ubiquitin: roles of E1 and E2 enzymes.
DR Reactome; R-MMU-9013420; RHOU GTPase cycle.
DR Reactome; R-MMU-9013424; RHOV GTPase cycle.
DR Reactome; R-MMU-9033241; Peroxisomal protein import.
DR BioGRID-ORCS; 22284; 19 hits in 73 CRISPR screens.
DR ChiTaRS; Usp9x; mouse.
DR PRO; PR:P70398; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; P70398; protein.
DR GO; GO:0045177; C:apical part of cell; IDA:MGI.
DR GO; GO:0005929; C:cilium; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0030426; C:growth cone; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0070410; F:co-SMAD binding; ISS:BHF-UCL.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; ISO:MGI.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0101005; F:deubiquitinase activity; IDA:UniProtKB.
DR GO; GO:1990380; F:Lys48-specific deubiquitinase activity; ISS:UniProtKB.
DR GO; GO:0061578; F:Lys63-specific deubiquitinase activity; ISS:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0048675; P:axon extension; IMP:UniProtKB.
DR GO; GO:0030509; P:BMP signaling pathway; ISS:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0016477; P:cell migration; IBA:GO_Central.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IMP:MGI.
DR GO; GO:0021698; P:cerebellar cortex structural organization; IMP:MGI.
DR GO; GO:0007059; P:chromosome segregation; IEA:UniProtKB-KW.
DR GO; GO:0021766; P:hippocampus development; IMP:MGI.
DR GO; GO:0001701; P:in utero embryonic development; IGI:MGI.
DR GO; GO:0032435; P:negative regulation of proteasomal ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0001764; P:neuron migration; IMP:UniProtKB.
DR GO; GO:1990138; P:neuron projection extension; IGI:MGI.
DR GO; GO:1901537; P:positive regulation of DNA demethylation; ISS:UniProtKB.
DR GO; GO:0032092; P:positive regulation of protein binding; ISS:UniProtKB.
DR GO; GO:1904515; P:positive regulation of TORC2 signaling; ISS:UniProtKB.
DR GO; GO:0009791; P:post-embryonic development; IMP:MGI.
DR GO; GO:0016579; P:protein deubiquitination; IMP:UniProtKB.
DR GO; GO:0071947; P:protein deubiquitination involved in ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:0070536; P:protein K63-linked deubiquitination; ISS:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; ISS:UniProtKB.
DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:0050856; P:regulation of T cell receptor signaling pathway; ISO:MGI.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; ISS:UniProtKB.
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 Biological rhythms; Cell cycle; Cell division; Cell projection;
KW Chromosome partition; Cytoplasm; Cytoskeleton; Hydrolase; Mitosis;
KW Phosphoprotein; Protease; Reference proteome; Thiol protease;
KW Ubl conjugation pathway.
FT CHAIN 1..2559
FT /note="Probable ubiquitin carboxyl-terminal hydrolase FAF-
FT X"
FT /id="PRO_0000080691"
FT DOMAIN 1557..1956
FT /note="USP"
FT REGION 1..64
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 967..999
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1592..1633
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2475..2559
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..49
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 967..993
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2502..2516
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2523..2537
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1566
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093,
FT ECO:0000305|PubMed:30951545"
FT ACT_SITE 1879
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT MOD_RES 374
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 375
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 588
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q93008"
FT MOD_RES 1600
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 2443
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 2540
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:17947660"
FT MOD_RES 2547
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q93008"
FT MOD_RES 2551
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q93008"
FT MUTAGEN 1566
FT /note="C->A: Abolished deubiquitinase activity."
FT /evidence="ECO:0000269|PubMed:30951545"
FT CONFLICT 73
FT /note="A -> P (in Ref. 1; AAB07731)"
FT /evidence="ECO:0000305"
FT CONFLICT 182
FT /note="C -> F (in Ref. 3; CAB01555)"
FT /evidence="ECO:0000305"
FT CONFLICT 1243..1244
FT /note="QK -> HQ (in Ref. 1; AAB07731)"
FT /evidence="ECO:0000305"
FT CONFLICT 1626
FT /note="D -> N (in Ref. 1; AAB07731)"
FT /evidence="ECO:0000305"
FT CONFLICT 1631
FT /note="S -> I (in Ref. 1; AAB07731)"
FT /evidence="ECO:0000305"
FT CONFLICT 1635
FT /note="D -> N (in Ref. 1; AAB07731)"
FT /evidence="ECO:0000305"
FT CONFLICT 1638
FT /note="E -> K (in Ref. 1; AAB07731)"
FT /evidence="ECO:0000305"
FT CONFLICT 1645
FT /note="R -> K (in Ref. 1; AAB07731)"
FT /evidence="ECO:0000305"
FT CONFLICT 1665
FT /note="R -> K (in Ref. 1; AAB07731)"
FT /evidence="ECO:0000305"
FT CONFLICT 1671
FT /note="F -> S (in Ref. 1; AAB07731)"
FT /evidence="ECO:0000305"
FT CONFLICT 1688..1689
FT /note="EF -> KS (in Ref. 1; AAB07731)"
FT /evidence="ECO:0000305"
FT CONFLICT 1918
FT /note="N -> T (in Ref. 1; AAB07731)"
FT /evidence="ECO:0000305"
FT CONFLICT 1930
FT /note="F -> L (in Ref. 1; AAB07731)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 2559 AA; 290711 MW; CC380E9F44B410DD CRC64;
MTATTRGSPV GGNDNQGQAP DGQSQPPLQQ NQTSSPDSSN ENSPATPPDE QGQGDAPPQI
EDEEPAFPHT DLAKLDDMIN RPRWVVPVLP KGELEVLLEA AIDLSKKGLD VKSEACQRFF
RDGLTISFTK ILTDEAVSGW KFEIHRCIIN NTHRLVELCV AKLAQDWFPL LELLAMALNP
HCKFHIYNGT RPCESVSSSV QLPEDELFAR SPDPRSPKGW LVDLLNKFGT LNGFQILHDR
FINGSALNVQ IIAALIKPFG QCYEFLTLHT VKKYFLPIIE MVPQFLENLT DEELKKEAKN
EAKNDALSMI IKSLKNLASR VPGQEETVKN LEIFRLKMIL RLLQISSFNG KMNALNEVNK
VISSVSYYTH RHGSSEDEEW LTAERMAEWI QQNNILSIVL RDSLHQPQYV EKLEKILRFV
IKEKALTLQD LDNIWAAQAG KHEAIVKNVH DLLAKLAWDF SPEQLDHLFD CFKASWTNAS
KKQREKLLEL IRRLAEDDKD GVMAHKVLNL LWNLAHSDDV PVDIMDLALS AHIKILDYSC
SQDRDTQKIQ WIDRFIEELR TNDKWVIPAL KQIREICSLF GEAPQNLSQS QRSPHVFYRH
DLINQLQHNH ALVTLVAENL ATYMESMRMY GRDNEDYDPQ TVRLGSRYSH VQEVQERLNF
LRFLLKDGQL WLCAPQAKQI WKCLAENAVY LCDREACFKW YSKLMGDEPD LDPDINKDFF
ESNVLQLDPS LLTENGMKCF ERFFKAVNCR EGKLVAKRRA YMMDDLELIG LDYLWRVVIQ
SNDDIACRAI DLLKEIYTNL GPRLQVNQVV IHEDFIQSCF DRLKASYDTL CVLDGDKDSI
NCARQEAVRM VRVLTVLREY INECDSDYHE ERTILPMSRA FRGKHLSFIV RFPNQGRQVD
DLEVWSHTND TIGSVRRCIL NRIKANVAHT KIELFVGGEL IDPGDDRKLI GQLNLKDKSL
ITAKLTQISS NMPSSPDSSS DSSTGSPGNH GNHYSDGPNP EVESCLPGVI MSLHPRYISF
LWQVADLGSS LNMPPLRDGA RVLMKLMPPD STTIEKLRAI CLDHAKLGES SLSPSLDSLF
FGPSASQVLY LTEVVYALLM PAGAPLTDDS SDFQFHFLKS GGLPLVLSML TRNNFLPNAD
METRRGAYLN ALKIAKLLLT AIGYGHVRAV AEACQPGVEG VNPMTSVNQV THDQAVVLQS
ALQSIPNPSS ECMLRNVSVR LAQQISDEAS RYMPDICVIR AIQKIIWTSG CGGLQLVFSP
NEEVTKIYEK TNAGNEPDLE DEQVCCEALE VMTLCFALIP TALDALSKEK AWQTFIIDLL
LHCHSKTVRQ VAQEQFFLMC TRCCMGHRPL LFFITLLFTV LGSTARERAK HSGDYFTLLR
HLLNYAYNSN INVPNAEVLL NNEIDWLKRI RDDVKRTGET GVEETILEGH LGVTKELLAF
QTPEKKFHIG CEKGGANLIK ELIDDFIFPA SNVYLQYMRN GELPAEQAIP VCGSPATINA
GFELLVALAV GCVRNLKQIV DSLTEMYYIG TAITTCEALT EWEYLPPVGP RPPKGFVGLK
NAGATCYMNS VIQQLYMIPS IRNGILAIEG TGSDVDDDMS GDEKQDNESN VDPRDDVFGY
PQQFEDKPPL SKTEDRKEYN IGVLRHLQVI FGHLAASRLQ YYVPRGFWKQ FRLWGEPVNL
REQHDALEFF NSLVDSLDEA LKALGHPAML SKVLGGSFAD QKICQGCPHR YECEESFTTL
NVDIRNHQNL LDSLEQYVKG DLLEGANAYH CEKCNKKVDT VKRLLIKKLP PVLAIQLKRF
DYDWERECAI KFNDYFEFPR ELDMEPYTVA GVAKLEGDNV NPESQLIQQN EQSESEKAGS
TKYRLVGVLV HSGQASGGHY YSYIIQRNGG DGEKNRWYKF DDGDVTECKM DDDEEMKNQC
FGGEYMGEVF DHMMKRMSYR RQKRWWNAYI LFYERMDTIG HDDEVIRYIS EIAITTRPHQ
IVMPSAIERS VRKQNVQFMH NRMQYSLEYF QFMKKLLTCN GVYLNPPPGQ DHLSPEAEEI
TMISIQLAAR FLFTTGFHTK KIVRGSASDW YDALCILLRH SKNVRFWFAH NVLFNVSNRF
SEYLLECPSA EVRGAFAKLI VFIAHFSLQD GPCPSPFASP GPSSQAYDNL SLSDHLLRAV
LNLLRREVSE HGRHLQQYFN LFVMYANLGV AEKTQLLKLS VPATFMLVSL DEGPGPPIKY
QYAELGKLYS VVSQLIRCCN VSSRMQSSIN GNPSLPNPFG DPNLSQPIMP IQQNVVDILF
VRTSYVKKII EDCSNSDETV KLLRFCCWEN PQFSSTVLSE LLWQVAYSYT YELRPYLDLL
LQILLIEDSW QTHRIHNALK GIPDDRDGLF DTIQRSKNHY QKRAYQCIKC MVALFSSCPV
AYQILQGNGD LKRKWTWAVE WLGDELERRP YTGNPQYTYN NWSPPVQSNE TSNGYFLERS
HSARMTLAKA CELCPEEEPD DQDAPDEHES PPPEDAPLYP HSPGSQYQQN NHVHGQPYTG
PAAHHMNNPQ RTGQRAQENY EGGEEVSPPQ TKGSVKCTY
