UHRF1_DANRE
ID UHRF1_DANRE Reviewed; 776 AA.
AC E7EZF3; Q1LUQ1; Q6DRP6; Q6PEI0;
DT 31-OCT-2012, integrated into UniProtKB/Swiss-Prot.
DT 08-MAR-2011, sequence version 1.
DT 03-AUG-2022, entry version 89.
DE RecName: Full=E3 ubiquitin-protein ligase UHRF1;
DE EC=2.3.2.27;
DE AltName: Full=RING-type E3 ubiquitin transferase UHRF1;
DE AltName: Full=Ubiquitin-like PHD and RING finger domain-containing protein 1;
DE AltName: Full=Ubiquitin-like-containing PHD and RING finger domains protein 1;
GN Name=uhrf1;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15256591; DOI=10.1073/pnas.0403929101;
RA Amsterdam A., Nissen R.M., Sun Z., Swindell E.C., Farrington S.,
RA Hopkins N.;
RT "Identification of 315 genes essential for early zebrafish development.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:12792-12797(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=AB;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=17242348; DOI=10.1073/pnas.0610774104;
RA Sadler K.C., Krahn K.N., Gaur N.A., Ukomadu C.;
RT "Liver growth in the embryo and during liver regeneration in zebrafish
RT requires the cell cycle regulator, uhrf1.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1570-1575(2007).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=21126517; DOI=10.1016/j.ydbio.2010.11.009;
RA Tittle R.K., Sze R., Ng A., Nuckels R.J., Swartz M.E., Anderson R.M.,
RA Bosch J., Stainier D.Y., Eberhart J.K., Gross J.M.;
RT "Uhrf1 and Dnmt1 are required for development and maintenance of the
RT zebrafish lens.";
RL Dev. Biol. 350:50-63(2011).
RN [6]
RP SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-649, AND MUTAGENESIS OF
RP SER-649.
RX PubMed=22072796; DOI=10.1091/mbc.e11-06-0487;
RA Chu J., Loughlin E.A., Gaur N.A., SenBanerjee S., Jacob V., Monson C.,
RA Kent B., Oranu A., Ding Y., Ukomadu C., Sadler K.C.;
RT "UHRF1 phosphorylation by cyclin A2/cyclin-dependent kinase 2 is required
RT for zebrafish embryogenesis.";
RL Mol. Biol. Cell 23:59-70(2012).
CC -!- FUNCTION: Multidomain protein that acts as a key epigenetic regulator
CC by bridging DNA methylation and chromatin modification. Specifically
CC recognizes and binds hemimethylated DNA at replication forks via its
CC YDG domain and recruits dnmt1 methyltransferase to ensure faithful
CC propagation of the DNA methylation patterns through DNA replication. In
CC addition to its role in maintenance of DNA methylation, also plays a
CC key role in chromatin modification: through its tudor-like regions and
CC PHD-type zinc fingers, specifically recognizes and binds histone H3
CC trimethylated at 'Lys-9' (H3K9me3) and unmethylated at 'Arg-2'
CC (H3R2me0), respectively, and recruits chromatin proteins. Enriched in
CC pericentric heterochromatin where it recruits different chromatin
CC modifiers required for this chromatin replication. Also localizes to
CC euchromatic regions where it negatively regulates transcription
CC possibly by impacting DNA methylation and histone modifications. Has E3
CC ubiquitin-protein ligase activity by mediating the ubiquitination of
CC target proteins. However, it is still unclear how E3 ubiquitin-protein
CC ligase activity is related to its role in chromatin in vivo (By
CC similarity). Required for pregastrula and lens development.
CC {ECO:0000250, ECO:0000269|PubMed:21126517}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27;
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00358}.
CC Cytoplasm {ECO:0000269|PubMed:22072796}. Note=Localizes to replication
CC foci. Enriched in pericentric heterochromatin. Also localizes to
CC euchromatic regions (By similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=E7EZF3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=E7EZF3-2; Sequence=VSP_044402;
CC -!- TISSUE SPECIFICITY: Expressed in proliferating tissues. Highly
CC expressed 24-48 hours after fertilization (hpf) in rapidly
CC proliferating tissues, including the tectum, retina and brachial
CC arches. Preferentially expressed in the liver bud and expression is
CC maintained in the fully developed liver. Also expressed in the proximal
CC gut. In adult, the highest expression is detected in testis.
CC {ECO:0000269|PubMed:17242348}.
CC -!- DOMAIN: The tudor-like regions specifically recognize and bind histone
CC H3 unmethylated at 'Arg-2' (H3R2me0), while the PHD-type zinc finger
CC specifically recognizes and binds histone H3 trimethylated at 'Lys-9'
CC (H3K9me3). {ECO:0000250}.
CC -!- DOMAIN: The YDG domain (also named SRA domain) specifically recognizes
CC and binds hemimethylated DNA at replication forks (DNA that is only
CC methylated on the mother strand of replicating DNA). {ECO:0000250}.
CC -!- DOMAIN: The RING finger is required for ubiquitin ligase activity.
CC {ECO:0000250}.
CC -!- PTM: Phosphorylation at Ser-649 is required for gastrulation.
CC {ECO:0000269|PubMed:22072796}.
CC -!- DISRUPTION PHENOTYPE: Embryos have a small head, eyes, jaw and an
CC underdeveloped gut. Moreover many mutants display diminished yolk
CC consumption and uninflated swim bladder as well as embryonic lethality.
CC DNA methylation is impaired during embryogenesis and embryos display
CC defects in lens development and maintenance. No fertility defects are
CC noted for heterozygous animals. {ECO:0000269|PubMed:17242348,
CC ECO:0000269|PubMed:21126517}.
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DR EMBL; AY648713; AAT68031.1; -; mRNA.
DR EMBL; BX927276; CAK04045.1; -; Genomic_DNA.
DR EMBL; FP360035; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC058055; AAH58055.1; -; mRNA.
DR RefSeq; NP_998242.1; NM_213077.1.
DR PDB; 6B9M; X-ray; 1.68 A; A/B/C=129-280.
DR PDBsum; 6B9M; -.
DR AlphaFoldDB; E7EZF3; -.
DR SMR; E7EZF3; -.
DR STRING; 7955.ENSDARP00000104481; -.
DR iPTMnet; E7EZF3; -.
DR PaxDb; E7EZF3; -.
DR PRIDE; E7EZF3; -.
DR Ensembl; ENSDART00000169317; ENSDARP00000135054; ENSDARG00000103409. [E7EZF3-2]
DR GeneID; 406350; -.
DR KEGG; dre:406350; -.
DR CTD; 29128; -.
DR ZFIN; ZDB-GENE-040426-2039; uhrf1.
DR eggNOG; ENOG502QRDQ; Eukaryota.
DR GeneTree; ENSGT00390000008296; -.
DR InParanoid; E7EZF3; -.
DR OMA; WYDAEIC; -.
DR OrthoDB; 705927at2759; -.
DR PhylomeDB; E7EZF3; -.
DR TreeFam; TF106434; -.
DR UniPathway; UPA00143; -.
DR PRO; PR:E7EZF3; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 22.
DR Bgee; ENSDARG00000103409; Expressed in early embryo and 35 other tissues.
DR GO; GO:0000785; C:chromatin; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:ZFIN.
DR GO; GO:0000791; C:euchromatin; ISS:UniProtKB.
DR GO; GO:0000792; C:heterochromatin; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:ZFIN.
DR GO; GO:0005657; C:replication fork; ISS:UniProtKB.
DR GO; GO:0044729; F:hemi-methylated DNA-binding; ISS:UniProtKB.
DR GO; GO:0042393; F:histone binding; ISS:UniProtKB.
DR GO; GO:0035064; F:methylated histone binding; ISS:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0031100; P:animal organ regeneration; IMP:ZFIN.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0010390; P:histone monoubiquitination; IBA:GO_Central.
DR GO; GO:0016574; P:histone ubiquitination; ISS:UniProtKB.
DR GO; GO:0044027; P:hypermethylation of CpG island; IMP:ZFIN.
DR GO; GO:0006954; P:inflammatory response; IMP:ZFIN.
DR GO; GO:0060729; P:intestinal epithelial structure maintenance; IMP:ZFIN.
DR GO; GO:0002088; P:lens development in camera-type eye; IMP:ZFIN.
DR GO; GO:0001889; P:liver development; IMP:ZFIN.
DR GO; GO:0010216; P:maintenance of DNA methylation; IMP:ZFIN.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0051865; P:protein autoubiquitination; ISS:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR Gene3D; 2.30.280.10; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR015947; PUA-like_sf.
DR InterPro; IPR036987; SRA-YDG_sf.
DR InterPro; IPR003105; SRA_YDG.
DR InterPro; IPR021991; TTD_dom.
DR InterPro; IPR000626; Ubiquitin-like_dom.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR InterPro; IPR045134; UHRF1/2-like.
DR InterPro; IPR019786; Zinc_finger_PHD-type_CS.
DR InterPro; IPR018957; Znf_C3HC4_RING-type.
DR InterPro; IPR011011; Znf_FYVE_PHD.
DR InterPro; IPR001965; Znf_PHD.
DR InterPro; IPR019787; Znf_PHD-finger.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR PANTHER; PTHR14140; PTHR14140; 1.
DR Pfam; PF00628; PHD; 1.
DR Pfam; PF02182; SAD_SRA; 1.
DR Pfam; PF12148; TTD; 1.
DR Pfam; PF00240; ubiquitin; 1.
DR Pfam; PF00097; zf-C3HC4; 1.
DR SMART; SM00249; PHD; 1.
DR SMART; SM00184; RING; 2.
DR SMART; SM00466; SRA; 1.
DR SMART; SM00213; UBQ; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR SUPFAM; SSF57903; SSF57903; 1.
DR SUPFAM; SSF88697; SSF88697; 1.
DR PROSITE; PS50053; UBIQUITIN_2; 1.
DR PROSITE; PS51015; YDG; 1.
DR PROSITE; PS01359; ZF_PHD_1; 1.
DR PROSITE; PS50016; ZF_PHD_2; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell cycle; Chromatin regulator;
KW Cytoplasm; DNA-binding; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Repressor; Transcription;
KW Transcription regulation; Transferase; Ubl conjugation pathway; Zinc;
KW Zinc-finger.
FT CHAIN 1..776
FT /note="E3 ubiquitin-protein ligase UHRF1"
FT /id="PRO_0000419988"
FT DOMAIN 1..78
FT /note="Ubiquitin-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00214"
FT DOMAIN 417..580
FT /note="YDG"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00358"
FT ZN_FING 297..364
FT /note="PHD-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146"
FT ZN_FING 706..745
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 88..126
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 135..201
FT /note="Tudor-like 1"
FT REGION 208..277
FT /note="Tudor-like 2"
FT REGION 278..298
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 290..299
FT /note="Linker"
FT /evidence="ECO:0000250"
FT REGION 331..335
FT /note="Histone H3R2me0 binding"
FT /evidence="ECO:0000250"
FT REGION 351..353
FT /note="Histone H3R2me0 binding"
FT /evidence="ECO:0000250"
FT REGION 443..444
FT /note="Required to promote base flipping"
FT /evidence="ECO:0000250"
FT REGION 464..467
FT /note="Required for formation of a 5-methylcytosine-binding
FT pocket"
FT /evidence="ECO:0000250"
FT REGION 476..479
FT /note="Required for formation of a 5-methylcytosine-binding
FT pocket"
FT /evidence="ECO:0000250"
FT REGION 617..660
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 94..124
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 461..462
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /ligand_part="5-methylcytosine group"
FT /ligand_part_id="ChEBI:CHEBI:65274"
FT /evidence="ECO:0000250"
FT BINDING 467
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /ligand_part="5-methylcytosine group"
FT /ligand_part_id="ChEBI:CHEBI:65274"
FT /evidence="ECO:0000250"
FT SITE 314
FT /note="Histone H3K4me0 binding"
FT /evidence="ECO:0000250"
FT SITE 325
FT /note="Histone H3R2me0 binding"
FT /evidence="ECO:0000250"
FT SITE 328
FT /note="Histone H3R2me0 binding"
FT /evidence="ECO:0000250"
FT SITE 477
FT /note="Required to confer preferential recognition of
FT cytosine over thymine"
FT /evidence="ECO:0000250"
FT SITE 487
FT /note="Required to discriminate between hemimethylated DNA
FT versus symmetrically methylated DNA"
FT /evidence="ECO:0000250"
FT SITE 489
FT /note="Required for affinity and specificity for 5-mCpG
FT sequence"
FT /evidence="ECO:0000250"
FT MOD_RES 649
FT /note="Phosphoserine; by CDK2"
FT /evidence="ECO:0000269|PubMed:22072796"
FT VAR_SEQ 293..294
FT /note="KG -> R (in isoform 2)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_044402"
FT MUTAGEN 649
FT /note="S->G: Non-phosphorylatable mutant; localizes only in
FT nucleus and is unable to localize in cytoplasm."
FT /evidence="ECO:0000269|PubMed:22072796"
FT CONFLICT 171..173
FT /note="AED -> PEE (in Ref. 3; AAH58055)"
FT /evidence="ECO:0000305"
FT CONFLICT 173
FT /note="D -> S (in Ref. 1; AAT68031)"
FT /evidence="ECO:0000305"
FT CONFLICT 207
FT /note="H -> R (in Ref. 3; AAH58055)"
FT /evidence="ECO:0000305"
FT CONFLICT 293..294
FT /note="KG -> SQ (in Ref. 1; AAT68031)"
FT /evidence="ECO:0000305"
FT CONFLICT 537
FT /note="S -> Y (in Ref. 1; AAT68031)"
FT /evidence="ECO:0000305"
FT CONFLICT 737
FT /note="K -> E (in Ref. 1; AAT68031 and 3; AAH58055)"
FT /evidence="ECO:0000305"
FT CONFLICT 754
FT /note="M -> V (in Ref. 3; AAH58055)"
FT /evidence="ECO:0000305"
FT STRAND 133..137
FT /evidence="ECO:0007829|PDB:6B9M"
FT STRAND 142..146
FT /evidence="ECO:0007829|PDB:6B9M"
FT TURN 148..150
FT /evidence="ECO:0007829|PDB:6B9M"
FT STRAND 152..164
FT /evidence="ECO:0007829|PDB:6B9M"
FT STRAND 173..180
FT /evidence="ECO:0007829|PDB:6B9M"
FT HELIX 184..186
FT /evidence="ECO:0007829|PDB:6B9M"
FT STRAND 189..191
FT /evidence="ECO:0007829|PDB:6B9M"
FT HELIX 193..195
FT /evidence="ECO:0007829|PDB:6B9M"
FT STRAND 196..198
FT /evidence="ECO:0007829|PDB:6B9M"
FT HELIX 206..208
FT /evidence="ECO:0007829|PDB:6B9M"
FT STRAND 214..219
FT /evidence="ECO:0007829|PDB:6B9M"
FT STRAND 221..223
FT /evidence="ECO:0007829|PDB:6B9M"
FT STRAND 229..240
FT /evidence="ECO:0007829|PDB:6B9M"
FT STRAND 242..251
FT /evidence="ECO:0007829|PDB:6B9M"
FT STRAND 255..257
FT /evidence="ECO:0007829|PDB:6B9M"
FT STRAND 260..266
FT /evidence="ECO:0007829|PDB:6B9M"
SQ SEQUENCE 776 AA; 87091 MW; 4B47035A83A6CD76 CRC64;
MWIQVRTMDG KETHRVDSLS KLTKVDELRV KIAELFNVEP ERQRLFYRGK QMEDGHTIFD
YNVGLNDIVQ LLVRQAVAAT VLPKDKEAEL SDSDSGCGSA QSESDKGSTH GESDVQSAGA
SGQTDTADLI DPGFGFYKIN EFVDARDLNM GAWFEAQIVK VTKTPAEDGG AEDIVYHVKY
EDYPENGVVQ LRGKDVRPRA RTVYQWHQLE PGMIVMVNYN PDDPKERGYW YDAEIQRKRE
TRTQREVFGK ILLGDAGDSL NDCRIMFVTE IYKIEEPGSA EGPGASSDSP LKKGSNGPEC
KVCKDDPKKN CRVCNCHVCG IKQDPDKQLL CDECDMAFHT YCLNPPLTTI PDDEDWYCPD
CRNDASEVVL AGEKLKESKK KAKMASASSS SQRDWGKGMA CVGRTKQCTI VPSNHYGPVP
GVPVGTLWKF RVQVSESGVH RPHVAGIHGR SNDGAYSLVL AGGYEDDVDD GNEFTYTGSG
GRDLSGNKRT AEQSCDQKLT NMNRALALNC NAAVNDKEGA EAKDWKAGKP VRVVRSSKGR
KHSKYSPEDG NRYDGIYKVV KYWPEKGKSG FLVWRYLLKR NDEESAPWTR DGKERIKKLG
LTMQYPEGYL EAVAAKEKEK ENKNEDDIEE TPTKGKRKRK SQSMEEKSSP TKGTPKKMKV
EAYKLSKEQK ALIKDDELNK KLWDEAMESL SLGPRFVNKV EEVFLCICCQ EVVYQPITTE
CQHNVCRECL QRSFKAKVYT CPACRHDLGK NYQMAVNKPL QAILTQLFPG YSSGRC
