DOA10_YEAST
ID DOA10_YEAST Reviewed; 1319 AA.
AC P40318; D6VVQ1;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=ERAD-associated E3 ubiquitin-protein ligase DOA10;
DE EC=2.3.2.27 {ECO:0000269|PubMed:31445887};
DE AltName: Full=RING-type E3 ubiquitin transferase DOA10 {ECO:0000305};
GN Name=SSM4; Synonyms=DOA10; OrderedLocusNames=YIL030C;
GN ORFNames=YI3299.01C, YI9905.18C;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 28383 / FL100 / VTT C-80102;
RX PubMed=7816042; DOI=10.1007/bf00290112;
RA Mandart E., Dufour M.-E., Lacroute F.;
RT "Inactivation of SSM4, a new Saccharomyces cerevisiae gene, suppresses mRNA
RT instability due to RNA14 mutations.";
RL Mol. Gen. Genet. 245:323-333(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169870;
RA Churcher C.M., Bowman S., Badcock K., Bankier A.T., Brown D.,
RA Chillingworth T., Connor R., Devlin K., Gentles S., Hamlin N., Harris D.E.,
RA Horsnell T., Hunt S., Jagels K., Jones M., Lye G., Moule S., Odell C.,
RA Pearson D., Rajandream M.A., Rice P., Rowley N., Skelton J., Smith V.,
RA Walsh S.V., Whitehead S., Barrell B.G.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome IX.";
RL Nature 387:84-87(1997).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [4]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=11641273; DOI=10.1101/gad.933301;
RA Swanson R., Locher M., Hochstrasser M.;
RT "A conserved ubiquitin ligase of the nuclear envelope/endoplasmic reticulum
RT that functions in both ER-associated and Matalpha2 repressor degradation.";
RL Genes Dev. 15:2660-2674(2001).
RN [5]
RP INTERACTION WITH CDC48; UBX2; UBC6 AND UBC7.
RX PubMed=16179953; DOI=10.1038/ncb1298;
RA Neuber O., Jarosch E., Volkwein C., Walter J., Sommer T.;
RT "Ubx2 links the Cdc48 complex to ER-associated protein degradation.";
RL Nat. Cell Biol. 7:993-998(2005).
RN [6]
RP FUNCTION, AND INTERACTION WITH UBX2; CDC48 AND UFD1.
RX PubMed=16179952; DOI=10.1038/ncb1299;
RA Schuberth C., Buchberger A.;
RT "Membrane-bound Ubx2 recruits Cdc48 to ubiquitin ligases and their
RT substrates to ensure efficient ER-associated protein degradation.";
RL Nat. Cell Biol. 7:999-1006(2005).
RN [7]
RP FUNCTION, AND IDENTIFICATION IN THE DOA10 COMPLEX.
RX PubMed=16873066; DOI=10.1016/j.cell.2006.05.043;
RA Carvalho P., Goder V., Rapoport T.A.;
RT "Distinct ubiquitin-ligase complexes define convergent pathways for the
RT degradation of ER proteins.";
RL Cell 126:361-373(2006).
RN [8]
RP FUNCTION.
RX PubMed=16437165; DOI=10.1038/sj.emboj.7600946;
RA Ravid T., Kreft S.G., Hochstrasser M.;
RT "Membrane and soluble substrates of the Doa10 ubiquitin ligase are degraded
RT by distinct pathways.";
RL EMBO J. 25:533-543(2006).
RN [9]
RP TOPOLOGY.
RX PubMed=16373356; DOI=10.1074/jbc.m512215200;
RA Kreft S.G., Wang L., Hochstrasser M.;
RT "Membrane topology of the yeast endoplasmic reticulum-localized ubiquitin
RT ligase Doa10 and comparison with its human ortholog TEB4 (MARCH-VI).";
RL J. Biol. Chem. 281:4646-4653(2006).
RN [10]
RP SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=17051211; DOI=10.1038/nature05170;
RA Deng M., Hochstrasser M.;
RT "Spatially regulated ubiquitin ligation by an ER/nuclear membrane ligase.";
RL Nature 443:827-831(2006).
RN [11]
RP FUNCTION IN CYTOSOLIC PROTEIN DEGRADATION.
RX PubMed=18812321; DOI=10.1074/jbc.m806424200;
RA Metzger M.B., Maurer M.J., Dancy B.M., Michaelis S.;
RT "Degradation of a cytosolic protein requires endoplasmic reticulum-
RT associated degradation machinery.";
RL J. Biol. Chem. 283:32302-32316(2008).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19779198; DOI=10.1126/science.1172867;
RA Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.;
RT "Global analysis of Cdk1 substrate phosphorylation sites provides insights
RT into evolution.";
RL Science 325:1682-1686(2009).
RN [13]
RP INTERACTION WITH PEX29.
RX PubMed=20159987; DOI=10.1074/jbc.m110.110551;
RA Liu C., van Dyk D., Xu P., Choe V., Pan H., Peng J., Andrews B., Rao H.;
RT "Ubiquitin chain elongation enzyme Ufd2 regulates a subset of Doa10
RT substrates.";
RL J. Biol. Chem. 285:10265-10272(2010).
RN [14]
RP FUNCTION IN N-ACETYLATED PROTEIN DEGRADATION.
RX PubMed=20110468; DOI=10.1126/science.1183147;
RA Hwang C.S., Shemorry A., Varshavsky A.;
RT "N-terminal acetylation of cellular proteins creates specific degradation
RT signals.";
RL Science 327:973-977(2010).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [16]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=31445887; DOI=10.1016/j.molcel.2019.07.006;
RA Matsumoto S., Nakatsukasa K., Kakuta C., Tamura Y., Esaki M., Endo T.;
RT "Msp1 clears mistargeted proteins by facilitating their transfer from
RT mitochondria to the ER.";
RL Mol. Cell 76:191-205(2019).
CC -!- FUNCTION: E3 ubiquitin-protein ligase which accepts ubiquitin
CC specifically from endoplasmic reticulum-associated UBC6 and UBC7 E2
CC ligases, and transfers it to substrates promoting their degradation
CC (PubMed:11641273, PubMed:16179952, PubMed:16437165, PubMed:16873066,
CC PubMed:17051211, PubMed:18812321, PubMed:20110468). Mediates the
CC degradation of a broad range of substrates, including endoplasmic
CC reticulum membrane proteins (ERQC), soluble nuclear proteins and
CC soluble cytoplasmic proteins (CytoQC) (PubMed:11641273,
CC PubMed:16179952, PubMed:16437165, PubMed:16873066, PubMed:17051211,
CC PubMed:18812321, PubMed:20110468). Component of the DOA10 ubiquitin
CC ligase complex, which is part of the ERAD-C pathway responsible for the
CC rapid degradation of membrane proteins with misfolded cytoplasmic
CC domains (PubMed:16873066). ERAD-C substrates are ubiquitinated through
CC DOA10 in conjunction with the E2 ubiquitin-conjugating enzymes UBC6 and
CC UBC7-CUE1 (PubMed:11641273, PubMed:16179952, PubMed:16437165,
CC PubMed:16873066, PubMed:17051211, PubMed:18812321, PubMed:20110468).
CC Ubiquitinated substrates are then removed to the cytosol via the action
CC of the UFD1-NPL4-CDC48/p97 (UNC) AAA ATPase complex and targeted to the
CC proteasome (PubMed:11641273, PubMed:16179952, PubMed:16437165,
CC PubMed:16873066, PubMed:17051211, PubMed:18812321, PubMed:20110468).
CC Also recognizes the N-terminally acetylated residue of proteins as
CC degradation signal (degron) (PubMed:20110468). N-terminally acetylated
CC target proteins include MATALPHA2, TBF1, SLK19, YMR090W, HIS3, HSP104,
CC UBP6 and ARO8 (PubMed:20110468). Catalyzes ubiquitination of
CC mislocalized tail-anchored proteins that are extracted from the
CC mitochondrion membrane by MSP1: following extraction, mistargeted
CC proteins are transferred to the endoplasmic reticulum, where they are
CC ubiquitinated by DOA10 and degraded by the proteasome
CC (PubMed:31445887). {ECO:0000269|PubMed:11641273,
CC ECO:0000269|PubMed:16179952, ECO:0000269|PubMed:16437165,
CC ECO:0000269|PubMed:16873066, ECO:0000269|PubMed:17051211,
CC ECO:0000269|PubMed:18812321, ECO:0000269|PubMed:20110468,
CC ECO:0000269|PubMed:31445887}.
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:0000269|PubMed:31445887};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:31445887}.
CC -!- SUBUNIT: Component of the DOA10 ubiquitin ligase complex which contains
CC E3 ligase SSM4/DOA10 and CDC48-binding protein UBX2/SEL1. The DOA10
CC complex interacts with the heterotrimeric CDC48-NPL4-UFD1 ATPase
CC complex which is recruited by UBX2/SEL1 via its interaction with CDC48.
CC Interacts with its associated ubiquitin conjugating enzymes UBC6 and
CC UBC7 with its membrane anchor CUE1. Interacts with PEX29.
CC {ECO:0000269|PubMed:16179952, ECO:0000269|PubMed:16179953,
CC ECO:0000269|PubMed:16873066, ECO:0000269|PubMed:20159987}.
CC -!- INTERACTION:
CC P40318; P25694: CDC48; NbExp=4; IntAct=EBI-18208, EBI-4308;
CC P40318; P38428: CUE1; NbExp=2; IntAct=EBI-18208, EBI-27580;
CC P40318; P12866: STE6; NbExp=3; IntAct=EBI-18208, EBI-18383;
CC P40318; Q04228: UBX2; NbExp=5; IntAct=EBI-18208, EBI-27730;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:11641273, ECO:0000269|PubMed:17051211}; Multi-pass
CC membrane protein {ECO:0000255}. Nucleus inner membrane
CC {ECO:0000269|PubMed:11641273, ECO:0000269|PubMed:17051211}; Multi-pass
CC membrane protein {ECO:0000255}.
CC -!- DOMAIN: The RING-CH-type zinc finger domain is required for E3 ligase
CC activity.
CC -!- SIMILARITY: Belongs to the DOA10/MARCH6 family. {ECO:0000305}.
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DR EMBL; X76715; CAA54133.1; -; Genomic_DNA.
DR EMBL; Z46881; CAA86961.1; -; Genomic_DNA.
DR EMBL; Z46861; CAA86921.1; -; Genomic_DNA.
DR EMBL; BK006942; DAA08517.1; -; Genomic_DNA.
DR PIR; S49951; S49951.
DR RefSeq; NP_012234.3; NM_001179380.3.
DR PDB; 2M6M; NMR; -; A=19-101.
DR PDBsum; 2M6M; -.
DR AlphaFoldDB; P40318; -.
DR BMRB; P40318; -.
DR SMR; P40318; -.
DR BioGRID; 34959; 260.
DR ComplexPortal; CPX-3074; Doa10 ubiquitin ligase complex.
DR DIP; DIP-7286N; -.
DR IntAct; P40318; 83.
DR MINT; P40318; -.
DR STRING; 4932.YIL030C; -.
DR TCDB; 3.A.16.1.2; the endoplasmic reticular retrotranslocon (er-rt) family.
DR iPTMnet; P40318; -.
DR MaxQB; P40318; -.
DR PaxDb; P40318; -.
DR PRIDE; P40318; -.
DR EnsemblFungi; YIL030C_mRNA; YIL030C; YIL030C.
DR GeneID; 854781; -.
DR KEGG; sce:YIL030C; -.
DR SGD; S000001292; SSM4.
DR VEuPathDB; FungiDB:YIL030C; -.
DR eggNOG; KOG1609; Eukaryota.
DR GeneTree; ENSGT00940000155171; -.
DR HOGENOM; CLU_006729_0_0_1; -.
DR InParanoid; P40318; -.
DR OMA; ALYFQYD; -.
DR BioCyc; MetaCyc:G3O-31303-MON; -.
DR BioCyc; YEAST:G3O-31303-MON; -.
DR BRENDA; 2.3.2.27; 984.
DR UniPathway; UPA00143; -.
DR PRO; PR:P40318; -.
DR Proteomes; UP000002311; Chromosome IX.
DR RNAct; P40318; protein.
DR GO; GO:0000837; C:Doa10p ubiquitin ligase complex; IDA:SGD.
DR GO; GO:0005783; C:endoplasmic reticulum; HDA:SGD.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IDA:SGD.
DR GO; GO:0016021; C:integral component of membrane; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005635; C:nuclear envelope; IDA:SGD.
DR GO; GO:0005637; C:nuclear inner membrane; IDA:SGD.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:SGD.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:SGD.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0071712; P:ER-associated misfolded protein catabolic process; IC:ComplexPortal.
DR GO; GO:0030970; P:retrograde protein transport, ER to cytosol; IDA:SGD.
DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; IMP:SGD.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR011016; Znf_RING-CH.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR Pfam; PF12906; RINGv; 1.
DR SMART; SM00744; RINGv; 1.
DR PROSITE; PS51292; ZF_RING_CH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Endoplasmic reticulum; Membrane; Metal-binding;
KW Nucleus; Reference proteome; Transferase; Transmembrane;
KW Transmembrane helix; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..1319
FT /note="ERAD-associated E3 ubiquitin-protein ligase DOA10"
FT /id="PRO_0000072214"
FT TOPO_DOM 1..131
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 132..152
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 153..203
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 204..224
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 225..468
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 469..489
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 490..491
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 492..512
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 513..626
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 627..647
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 648..660
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 661..681
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 682..739
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 740..760
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 761..777
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 778..797
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 798..965
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 966..986
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 987..1019
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 1020..1040
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1041..1113
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1114..1134
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1135..1168
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 1169..1189
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1190..1213
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1214..1234
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1235..1270
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 1271..1291
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1292..1319
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT ZN_FING 31..100
FT /note="RING-CH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT REGION 291..315
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 329..381
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 291..306
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 342..356
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 39
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 42
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 56
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 58
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 66
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 69
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 90
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 93
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT CONFLICT 241
FT /note="L -> F (in Ref. 1; CAA54133)"
FT /evidence="ECO:0000305"
FT CONFLICT 743
FT /note="A -> T (in Ref. 1; CAA54133)"
FT /evidence="ECO:0000305"
FT CONFLICT 1085
FT /note="N -> D (in Ref. 1; CAA54133)"
FT /evidence="ECO:0000305"
FT CONFLICT 1186
FT /note="Y -> F (in Ref. 1; CAA54133)"
FT /evidence="ECO:0000305"
FT STRAND 40..42
FT /evidence="ECO:0007829|PDB:2M6M"
FT STRAND 48..50
FT /evidence="ECO:0007829|PDB:2M6M"
FT HELIX 67..76
FT /evidence="ECO:0007829|PDB:2M6M"
FT STRAND 91..93
FT /evidence="ECO:0007829|PDB:2M6M"
SQ SEQUENCE 1319 AA; 151455 MW; 3EDFF7F9D90A0C8C CRC64;
MDVDSDVNVS RLRDELHKVA NEETDTATFN DDAPSGATCR ICRGEATEDN PLFHPCKCRG
SIKYMHESCL LEWVASKNID ISKPGADVKC DICHYPIQFK TIYAENMPEK IPFSLLLSKS
ILTFFEKARL ALTIGLAAVL YIIGVPLVWN MFGKLYTMML DGSSPYPGDF LKSLIYGYDQ
SATPELTTRA IFYQLLQNHS FTSLQFIMIV ILHIALYFQY DMIVREDVFS KMVFHKIGPR
LSPKDLKSRL KERFPMMDDR MVEYLAREMR AHDENRQEQG HDRLNMPAAA ADNNNNVINP
RNDNVPPQDP NDHRNFENLR HVDELDHDEA TEEHENNDSD NSLPSGDDSS RILPGSSSDN
EEDEEAEGQQ QQQQPEEEAD YRDHIEPNPI DMWANRRAQN EFDDLIAAQQ NAINRPNAPV
FIPPPAQNRA GNVDQDEQDF GAAVGVPPAQ ANPDDQGQGP LVINLKLKLL NVIAYFIIAV
VFTAIYLAIS YLFPTFIGFG LLKIYFGIFK VILRGLCHLY YLSGAHIAYN GLTKLVPKVD
VAMSWISDHL IHDIIYLYNG YTENTMKHSI FIRALPALTT YLTSVSIVCA SSNLVSRGYG
RENGMSNPTR RLIFQILFAL KCTFKVFTLF FIELAGFPIL AGVMLDFSLF CPILASNSRM
LWVPSICAIW PPFSLFVYWT IGTLYMYWFA KYIGMIRKNI IRPGVLFFIR SPEDPNIKIL
HDSLIHPMSI QLSRLCLSMF IYAIFIVLGF GFHTRIFFPF MLKSNLLSVP EAYKPTSIIS
WKFNTILLTL YFTKRILESS SYVKPLLERY WKTIFKLCSR KLRLSSFILG KDTPTERGHI
VYRNLFYKYI AAKNAEWSNQ ELFTKPKTLE QAEELFGQVR DVHAYFVPDG VLMRVPSSDI
VSRNYVQTMF VPVTKDDKLL KPLDLERIKE RNKRAAGEFG YLDEQNTEYD QYYIVYVPPD
FRLRYMTLLG LVWLFASILM LGVTFISQAL INFVCSFGFL PVVKLLLGER NKVYVAWKEL
SDISYSYLNI YYVCVGSVCL SKIAKDILHF TEGQNTLDEH AVDENEVEEV EHDIPERDIN
NAPVNNINNV EEGQGIFMAI FNSIFDSMLV KYNLMVFIAI MIAVIRTMVS WVVLTDGILA
CYNYLTIRVF GNSSYTIGNS KWFKYDESLL FVVWIISSMV NFGTGYKSLK LFFRNRNTSK
LNFLKTMALE LFKQGFLHMV IYVLPIIILS LVFLRDVSTK QIIDISHGSR SFTLSLNESF
PTWTRMQDIY FGLLIALESF TFFFQATVLF IQWFKSTVQN VKDEVYTKGR ALENLPDES
