R213A_DANRE
ID R213A_DANRE Reviewed; 5209 AA.
AC A0A0R4IBK5;
DT 16-MAR-2016, integrated into UniProtKB/Swiss-Prot.
DT 20-JAN-2016, sequence version 1.
DT 03-AUG-2022, entry version 38.
DE RecName: Full=E3 ubiquitin-protein ligase rnf213-alpha {ECO:0000305};
DE EC=2.3.2.27 {ECO:0000250|UniProtKB:Q63HN8};
DE EC=3.6.4.- {ECO:0000250|UniProtKB:Q63HN8};
DE AltName: Full=E3 ubiquitin-lipopolysaccharide ligase rnf213-alpha {ECO:0000305};
DE EC=2.3.2.- {ECO:0000250|UniProtKB:Q63HN8};
DE AltName: Full=Mysterin-A {ECO:0000303|PubMed:30705059};
DE AltName: Full=Mysterin-alpha {ECO:0000303|PubMed:26530008};
DE AltName: Full=RING finger protein 213-A {ECO:0000305};
DE AltName: Full=RING finger protein 213-alpha {ECO:0000303|PubMed:21799892};
GN Name=rnf213a {ECO:0000303|PubMed:27125596};
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 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 [2]
RP DISRUPTION PHENOTYPE.
RX PubMed=21799892; DOI=10.1371/journal.pone.0022542;
RA Liu W., Morito D., Takashima S., Mineharu Y., Kobayashi H., Hitomi T.,
RA Hashikata H., Matsuura N., Yamazaki S., Toyoda A., Kikuta K., Takagi Y.,
RA Harada K.H., Fujiyama A., Herzig R., Krischek B., Zou L., Kim J.E.,
RA Kitakaze M., Miyamoto S., Nagata K., Hashimoto N., Koizumi A.;
RT "Identification of RNF213 as a susceptibility gene for moyamoya disease and
RT its possible role in vascular development.";
RL PLoS ONE 6:E22542-E22542(2011).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=26530008; DOI=10.1038/srep16161;
RA Kotani Y., Morito D., Yamazaki S., Ogino K., Kawakami K., Takashima S.,
RA Hirata H., Nagata K.;
RT "Neuromuscular regulation in zebrafish by a large AAA+ ATPase/ubiquitin
RT ligase, mysterin/RNF213.";
RL Sci. Rep. 5:16161-16161(2015).
RN [4]
RP DISRUPTION PHENOTYPE.
RX PubMed=27125596; DOI=10.1016/j.brainres.2016.04.051;
RA Wen J., Sun X., Chen H., Liu H., Lai R., Li J., Wang Y., Zhang J.,
RA Sheng W.;
RT "Mutation of rnf213a by TALEN causes abnormal angiogenesis and circulation
RT defects in zebrafish.";
RL Brain Res. 1644:70-78(2016).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=30705059; DOI=10.1083/jcb.201712120;
RA Sugihara M., Morito D., Ainuki S., Hirano Y., Ogino K., Kitamura A.,
RA Hirata H., Nagata K.;
RT "The AAA+ ATPase/ubiquitin ligase mysterin stabilizes cytoplasmic lipid
RT droplets.";
RL J. Cell Biol. 218:949-960(2019).
CC -!- FUNCTION: Atypical E3 ubiquitin ligase that can catalyze ubiquitination
CC of both proteins and lipids, and which is involved in various
CC processes, such as lipid metabolism, angiogenesis and cell-autonomous
CC immunity (By similarity). Acts as a key immune sensor by catalyzing
CC ubiquitination of the lipid A moiety of bacterial lipopolysaccharide
CC (LPS) via its RZ-type zinc-finger: restricts the proliferation of
CC cytosolic bacteria, such as Salmonella, by generating the bacterial
CC ubiquitin coat through the ubiquitination of LPS (By similarity).
CC Ubiquitination of LPS triggers cell-autonomous immunity, such as
CC antibacterial autophagy, leading to degradation of the microbial
CC invader (By similarity). Involved in lipid metabolism by regulating fat
CC storage and lipid droplet formation; act by inhibiting the lipolytic
CC process (PubMed:30705059). Also regulates lipotoxicity by inhibiting
CC desaturation of fatty acids (By similarity). Also acts as an E3
CC ubiquitin-protein ligase via its RING-type zinc finger (By similarity).
CC Involved in the non-canonical Wnt signaling pathway in vascular
CC development: acts by mediating ubiquitination and degradation of
CC proteins downstream of rspo3, leading to inhibit the non-canonical Wnt
CC signaling pathway and promoting vessel regression (By similarity). Also
CC has ATPase activity; ATPase activity is required for ubiquitination of
CC LPS (By similarity). Also involved in neuromuscular regulation
CC (PubMed:26530008). {ECO:0000250|UniProtKB:Q63HN8,
CC ECO:0000269|PubMed:26530008, ECO:0000269|PubMed:30705059}.
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; Evidence={ECO:0000250|UniProtKB:Q63HN8};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:Q63HN8};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13066;
CC Evidence={ECO:0000250|UniProtKB:Q63HN8};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000250|UniProtKB:Q63HN8}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q63HN8}. Lipid droplet
CC {ECO:0000250|UniProtKB:Q63HN8}.
CC -!- DOMAIN: Composed of an N-terminal stalk, a dynein-like core comprised
CC of two catalytically active and four inactive ATPase domains, and a C-
CC terminal E3 module. The ATPase regions do not generate movement but
CC rather act like an intricate molecular 'switch'.
CC {ECO:0000250|UniProtKB:E9Q555}.
CC -!- DOMAIN: The RING-type zinc finger domain is required for the ubiquitin-
CC protein ligase activity. {ECO:0000250|UniProtKB:Q63HN8}.
CC -!- DOMAIN: The RZ-type (RNF213-ZNFX1) zinc-finger is required for the
CC ubiquitination of the lipid A moiety of bacterial lipopolysaccharide
CC (LPS). {ECO:0000250|UniProtKB:Q63HN8}.
CC -!- DISRUPTION PHENOTYPE: Morpholino knockdown leads to a slight reduction
CC in body size, a small eye and a wavy trunk (PubMed:21799892). Fishes
CC develope abnormal angiogenesis in intersegmental vessels and cranial
CC secondary vessels (PubMed:21799892, PubMed:27125596). Abnormal
CC sprouting vessels are observed in the trunk and head regions, while
CC axial trunk vessels, the dorsal aorta and posterior cardinal vein
CC proceed almost normally (PubMed:21799892). Morpholino knockdown in
CC larvae leads to a reduction in fast myofibrils and immature projection
CC of primary motoneurons, leading to severe motor deficits
CC (PubMed:26530008). Decreased lipid droplet formation (PubMed:30705059).
CC {ECO:0000269|PubMed:21799892, ECO:0000269|PubMed:26530008,
CC ECO:0000269|PubMed:27125596, ECO:0000269|PubMed:30705059}.
CC -!- SIMILARITY: Belongs to the AAA ATPase family. {ECO:0000305}.
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DR EMBL; CABZ01009724; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CABZ01009732; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CR759836; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; XP_009298091.1; XM_009299816.2.
DR SMR; A0A0R4IBK5; -.
DR STRING; 7955.ENSDARP00000103579; -.
DR PaxDb; A0A0R4IBK5; -.
DR Ensembl; ENSDART00000168133; ENSDARP00000130268; ENSDARG00000099465.
DR ZFIN; ZDB-GENE-050302-100; rnf213a.
DR eggNOG; ENOG502QQ65; Eukaryota.
DR GeneTree; ENSGT00630000089884; -.
DR OMA; NAYMKDM; -.
DR OrthoDB; 840at2759; -.
DR Reactome; R-DRE-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR PRO; PR:A0A0R4IBK5; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 3.
DR Bgee; ENSDARG00000099465; Expressed in granulocyte and 20 other tissues.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005811; C:lipid droplet; ISS:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; ISS:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IBA:GO_Central.
DR GO; GO:0008015; P:blood circulation; IMP:ZFIN.
DR GO; GO:0042742; P:defense response to bacterium; ISS:UniProtKB.
DR GO; GO:0002376; P:immune system process; IEA:UniProtKB-KW.
DR GO; GO:0140042; P:lipid droplet formation; IMP:UniProtKB.
DR GO; GO:0120323; P:lipid ubiquitination; ISS:UniProtKB.
DR GO; GO:2000051; P:negative regulation of non-canonical Wnt signaling pathway; IBA:GO_Central.
DR GO; GO:0070534; P:protein K63-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0019216; P:regulation of lipid metabolic process; ISS:UniProtKB.
DR GO; GO:0002040; P:sprouting angiogenesis; IMP:ZFIN.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0098792; P:xenophagy; ISS:UniProtKB.
DR Gene3D; 3.30.40.10; -; 1.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR031248; RNF213.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR PANTHER; PTHR22605; PTHR22605; 1.
DR SMART; SM00382; AAA; 2.
DR SMART; SM00184; RING; 2.
DR SUPFAM; SSF52540; SSF52540; 2.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
DR PROSITE; PS51981; ZF_RZ; 1.
PE 3: Inferred from homology;
KW Angiogenesis; ATP-binding; Cytoplasm; Hydrolase; Immunity; Lipid droplet;
KW Lipid metabolism; Metal-binding; Multifunctional enzyme;
KW Nucleotide-binding; Reference proteome; Transferase;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..5209
FT /note="E3 ubiquitin-protein ligase rnf213-alpha"
FT /id="PRO_0000435804"
FT ZN_FING 4005..4043
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 4487..4557
FT /note="RZ-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01325"
FT REGION 27..373
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 27..80
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 85..99
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 117..131
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 132..201
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 203..221
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 222..266
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 267..286
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 287..311
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 326..358
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 359..373
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 4518
FT /note="Nucleophile; for E3 ubiquitin-lipopolysaccharide
FT ligase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01325"
FT BINDING 2036..2041
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:E9Q555"
FT BINDING 2135
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:E9Q555"
FT BINDING 2193
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:E9Q555"
FT BINDING 2252
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:E9Q555"
FT BINDING 2535
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:E9Q555"
FT BINDING 2610
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:E9Q555"
FT BINDING 4005
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:E9Q555"
FT BINDING 4008
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:E9Q555"
FT BINDING 4020
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:E9Q555"
FT BINDING 4022
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:E9Q555"
FT BINDING 4025
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:E9Q555"
FT BINDING 4028
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:E9Q555"
FT BINDING 4040
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:E9Q555"
FT BINDING 4043
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:E9Q555"
FT BINDING 4507
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01325"
FT BINDING 4511
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01325"
FT BINDING 4527
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01325"
FT BINDING 4530
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01325"
SQ SEQUENCE 5209 AA; 596751 MW; EA4307D9515399F3 CRC64;
MKCPKCSHEA LEKAPKFCSE CGHKLQSQSY ETTQGTPHDK SQTPSIVPQI TNAEMDETGS
ESKSLEIQNA NVSPKRPNEN TSPNPKKKKR KKRKKEKKKK SGVSEGPSSL TSDLSDISLT
DKEKKMDTDQ SSDSDCSSCI VEDTPTPAEP SSHLSPPENE TAGPAQLSAS ALTTGSSKDG
EESIGTTQKP VSASASKAPL GVDQQTKEEK VKCKDEGQKS LSAKAQHTPN ANVDQNANVQ
SDANIDKDSQ NVEPQKSSSV KTKPSKSTVA DPKKTESEKQ KSGERDNENS TQPVSSPKLK
RNQTEESQKM VFGPNSAPKK NRGSSADSAM KVEKKPAGGK KDSSADQKSK ESEDTESQCV
TLPKRNTRST QHISSSDRLT IYFHAVLSKD FKFNPEEDLI FIRAGGPIGN WEENLVELSV
SRDLKEHGFL VEGKFICRKI DAEAVSIPYK YVVYKQKKNK YDYEYIYKLD AEVPTNRCLF
IKSHLLNDEG EWHQYDDIIC AQPAKNMFEW VKKTIWSDEK KNVLQGRKIA GTIMLETIFD
LLRSWSKINL NNFFSQLRQF YEIYRNPFVF EKKQTKWYQL DYDEKDVREL LKNFMLMHVT
PELQKDSNEK SKFIQEPLKA GLIMLYVWKQ YDLKLDYGTL SRLCTAVCLP NLPKDEFLSL
WTDITESFSV INSFSDMVEA LISKLKAENM PRWIIVIPLL HLLKGTSKPF EQVITKVNSK
YEQSWAGLQG LRSNILSPGP QERRAMLNLM KTYGHLVEVD RLLIRSWMYL MPLDDLVECG
SIFPVELLDI LQLFTMKCPN NISFTSSEST AEALAHIQSQ LLQHRYSCPD VDYGIQCIQA
ACKLLEKICS LVRYFGHSQN FTDIPVACMN LVASVSGFAQ TKQEADTFAE KTLVLLNDTK
QTVRAWMRQT FKGRLLNSHL FSSHLTGTSF STETEVWNNI IAIDFVCKDF IKEWRDTFTT
DFEGKYQQED HLDQIEAYCS NIEKLKVSQP YLVNSVEKCA LQAVSTICQT KSEWKLFARF
NKFRINWRFG NLVSTIILKS WPKDDKGTYF EEEEAVLKHL LGWAAAKNIF QLHGADEKLI
DQLSDEAKEK FAMATSLFTN VLNQLVTGKI KMKLLNHILE KKSVFLELLT LDCFSEEEQY
KDIDAMKALI QTRQEEVKAI YHERALAGAL IAMCHNVEEH VKVDYKYLED LYSNDMNEMD
LDLFMDVHEL NQIPTEASLE VPYFELQDDV RSMAEILNIF KDSYIFKLRW GNEAALFVER
AEDEELDELD ELPITLDVLN EEIFLPCHAA YRNIYTSLKD GSIDFEDIDE IFRAYKGKYE
KLAAEVAIMS KQDFNDDQHW VQTRIQQIKQ YHELHLAVES AKVVMMVKET LCLQGDFQVL
EKLLITTHSD FKSERLDSID NELIQAKNVL VDITEPRRLC LQELGHRKNF VIWVKEALED
INELKVFVDL ASISAGENDL DVDRVACFHD AVLGYSSMLY DLKPDAGFSL FNEMLKKLWK
ALDNDSNLPK KLCDSARHIE WLKTVKDSHG SVELSSLSLA SAINSKGIYV INAQNQKKLA
LENILKLHIM EEHDGGCETR VYSLEDLRDL QNKLMLMSGK GEQGQCEVDQ FAEVFASVQR
LVSAFIDLYV AGNPLFRHWE ANINCNSKEA CIIIDFNLGS VVSVVMVEGD VTEQLPEVCK
KMESCLRFWQ DFMDKQRSQH YYLNYYTAEQ LVYLCHQLAH NNMEEIDDQV LMMLSFIKPS
CSTSDLRKAW HILQYDLIRK GPDQNDDLDF QTFVEVSSMT ENESTEKSCP TSDDLIQQLG
DASGSTKLGV IWNNYMRDMK AFLPDSLDVP SLGYLLEILA NSHREDEGDM SQRDKTRTIL
RELPNGIASG RPNLIICPSE EILISCISIY MNSKNEPLPT YDEVLLCSAT TPYEEVELFL
RRCLSAGYRG KKIYTMLYVN QLNYEVSYKV EKFFQNQNAH TTNDYRLVLI CESNKEHAYL
PSAFSQFRLH LIPQQPIPSI QQYLHRHFAV PVGISSAAAV FKDRQNVGVV SSERSGVGKS
LYIKRLYEKL KLNSKKPSQL KCIRLTEPKV DENVIIQSLI SVLKKNDLSV YHFDVTTMVK
KGLHEFLFRL LILGYLMDSK GNMWKSSNKH LYVIEILRPG LSQNDRRAGA KVSFNFLDVF
PIVYCRSPKE VLELEMRMEE HPSFGLSDDP LMDDQEFRSE AYQRPYQYLQ RFYNGINLDE
FLYQGVEGSH VECLQMLFEY CGIIDPSWAE LRNFAWFLNL QLQDCEKSVF CDFSFVGDTL
LGFKNFVVEF MILMAKDFAT PSLSISDQSP GRLHEDFSSA NEEDLAPFKI RKRWESEPHP
YIFFNDDHDS MTFIGFHLQP NAQKGVDAVD PSNNRVIKQN IMTMELYEGL KLQRVPFNID
FDQLPRWEKI ERLSRVLGIQ WPLDPDETYE LTTDNMLKML AVHMRFRCGI PVIIMGETGC
GKTRLIKFLC EMHRSGVATD NMKLVKVHGG TSSEMIYTKV REAEAMALRN KLDYGFDTVL
FFDEANTTEA ISSIKEILCD NSAEGQNLTE NTGLKIIAAC NPYRKHTDVM IKRLESAGLG
YRVRAEETDE KLGSIPLRQL VYRVQALPPS MIPLIWDFGQ LNDHTEKMYI KQIVERVAET
HSIDSGYITV ITDVLSASQK YMRTRQDECS FVSLRDVERC MQVFGWFYKK HLMLLSELDK
FESIQRTEKT DQHPKDTDER NPILWSLLMA VGVCYHACLE DKEKYRKKIC KYFPAAYSPM
KVMQEISVIQ DIFLEGVPMG ENIARNNALK ENVFMMVICI ELRIPLFLVG KPGSSKSLSK
TLVADGMQGQ AAHSDLFRKL KQIHLVSFQC SPHSTPEGII NTFKQCARFQ EGKNLSEYVS
VVVLDEIGLA EDSQKMPLKT LHPLLEEGCI DDQPSPHKKV GFIGISNWAL DPAKMNRGIF
VSRGDPDENE LIESAKGICS SDVMILEKVR ECFKPFAHAY LRICKKQEKG FFGLRDYYSL
IKMMFAVAKA CDQKPSAEQI VKAVLRNFSG KDDVDAVTFF TSRLNIKPEL ETISAIELVR
ENVTAIGQDE ECRYLLVLTK NYAALRILQQ TFFSDQCQPE IIFGSSFPKD QEYTQICRNI
NRVKICMETG QTIVLLNLQN LYESLYDALN QYYVTLGGQK YVDLGLGTHR VKCRVHKDFR
LIVIEEKDIV YKQFPIPLIN RLEKHYLDLN TLLKSEQKDI VKNLEQWVQC FTDVKNKHSV
APSARRYSPA DAFIGYHTDT CASVVMQVTE QLKGQELSDP RKGILDESKL ILLNCATPDA
VVRLDCTSLF NVESEHLSRV YFEDQMHNSL AEFILSHIQQ EGCSGAFFTE VTTFSRLLTA
SETQQLQNVV QNIELLSLQQ FDTEQSFLKK IKNYLENTTG DKILLIQTDF DEGFQKLNVI
ASAKYSSINE INKFKKEGSG KIFVYFITKL PRMDGGTSYI GFNGGPWKSI HIDDLRRPKD
IVSDIKALQG LTISQLFEEK AEKVDETEAM EVEDMYAGGE DEEDEEKMEL EENNGCKDVL
DTTALVRSCV QSAVGMLRDQ TEGGMRSTKR VEILLMLLAE DQTLQAEFLK TLKTRLHSLL
VAHDDNTISA KSWVSREALN VDALHEGGTF RHALWRRVQA VVTPFLAQLV SVVDRDCNLD
LLLDRNSGEP LKKLWLEIFR DDKFLSVSPY TRTENNSATK TILVQNYMSV DRNKGCTMPF
SWRIKDYLED LWKHALQQEG HTVKQFEEFF WKTPLGRYIS EATNEMQMEF FYRYLQDFIS
MTMNVTSEVD FEVLRGAFTS SVNEVRIAHE AHESEALSLV WIHVAYHHFK NRIQNLHRMM
SLEPQISQML LENRYASEGK ELVLDVLAAV ACIEYLEPQN LDGDDQSLAW LRRVKKLQVP
VELVCSLESL HNRGDRCRQM VTNIQHGWRR IYSLVLFVEH MLLGVGDLQQ KLKPVVLEHT
QLLAQVLEQD SNLKKKKPFE AVITVLKTCK DKASQRIIRF GLQLCPVCMG DPRDPLSLPC
DHIYCLTCIR QWLVPGQMHC PLCVQEVPDN FELKPSDELR RLISQNASFR MRCNAFFIDL
VSTMCFKDNT PPSKDIILHL LSLLMVEASS LPPFKGRDRR FLTKALSPFD DSVDKNPVVR
SVVLKLLLNY SFDHVKDYLQ QHLTEVEQSK ILEETDKAEL YCLYMNCLED SMYDRTQWHT
VAEQQNCFLE ETRFLLEFLQ SDSVSAHTAT VEHLQRLARV RLCLDMAADL LVANAGIHDD
PSAFIQAFWN NVVNLCRQSR NDWYRVYLIR KLCSLQGVEC VKNLLLQETY RWLFPQEILE
MNQDDSQIDQ YLACGADYKT IRDAVAKFML DLHINGIQKA IEDCNCTPMK KAVYVLMAFF
REVTSLHRTG NPNMHPKPEH CAGLEHFIKN SAIFVNNEMK AFAEKLVRNQ LGALRVRPHM
PSRDLSLVEV TIHMAAVLLC GNLLLLQPLQ KLALSPNNMM ASFIPTMPDD MLAVAQQAMG
HLQWYFCPNG HPCTVGECGQ PMEVSRCPDC DAEIGGSNHR PVDGFRAMQI QADRTQSGHI
LGDAQRRDLP DMQDTKNMSP APFALLRLLT HMSMLIGTQN NPQSIMQIIK PAVVHPDAFL
MQHLLKDMEQ LSKALGKGVD DTVSTIHLAI HSLLEPHQTS QWPDPYDPNL STKDARNGWE
NAMNNDVITH HLKVLEHQLK EVNAFIREDE RVSSNPVMKL TFGEPGRFLR SLPQNSLIHN
SSIWSCRNKV SLMSLTHIVE QNNGRDTLPV LWRFLQREAE LRLVRFLPDI LVLQRDLVKK
FQNITDLTYK TIREFLQDQK AASLTAWYEK RIKIFLTTWN QIRVSLANTG EIKLPADYTE
KDLGLDADLQ VLLPQRRGLG LCSTALVSYL ITIHNDLMYT VEKHTGDDSD YKISPAELTE
LHVIRYEYDR DLLPLVLANC QYSMECGQET LLEYDLPKIQ QQILTRFLQG KPLITINGIP
TLVNRQDRNY EIIFKDVKGK VQQELLQPLT QYDLVKELQS YSDVCEALST VELAVGFLAM
TGGEPNMQLG VYLKDVLQMT DHMATHVFKA LSRCSLKHCV ALWQLLSSLK SETMLRLKRD
PFVGISKEYK QPLQEEHKRL LTSFFTKSSA DAFLLEMHEF LLLVLKSPKA TDTYRPDWRL
KHTVVSYMER KDLDVPPEVE EFFPKEILLS EYTSTWNFSV NLRQKRSQS
