ID   AP3A_SARS2              Reviewed;         275 AA.
AC   P0DTC3;
DT   22-APR-2020, integrated into UniProtKB/Swiss-Prot.
DT   22-APR-2020, sequence version 1.
DT   28-JUN-2023, entry version 17.
DE   RecName: Full=ORF3a protein;
DE            Short=ORF3a;
DE   AltName: Full=Accessory protein 3a;
DE   AltName: Full=Protein 3a;
DE   AltName: Full=Protein U274;
DE   AltName: Full=Protein X1;
GN   ORFNames=3a;
OS   Severe acute respiratory syndrome coronavirus 2 (2019-nCoV) (SARS-CoV-2).
OC   Viruses; Riboviria; Orthornavirae; Pisuviricota; Pisoniviricetes;
OC   Nidovirales; Cornidovirineae; Coronaviridae; Orthocoronavirinae;
OC   Betacoronavirus; Sarbecovirus.
OX   NCBI_TaxID=2697049;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=32015508; DOI=10.1038/s41586-020-2008-3;
RA   Wu F., Zhao S., Yu B., Chen Y.-M., Wang W., Song Z.-G., Hu Y., Tao Z.-W.,
RA   Tian J.-H., Pei Y.-Y., Yuan M.-L., Zhang Y.-L., Dai F.-H., Liu Y.,
RA   Wang Q.-M., Zheng J.-J., Xu L., Holmes E.C., Zhang Y.-Z.;
RT   "A new coronavirus associated with human respiratory disease in China.";
RL   Nature 579:265-269(2020).
RN   [2]
RP   SUBCELLULAR LOCATION.
RX   PubMed=33060197; DOI=10.1126/science.abe9403;
RG   QCRG Structural Biology Consortium;
RG   Zoonomia Consortium;
RA   Gordon D.E., Hiatt J., Bouhaddou M., Rezelj V.V., Ulferts S., Braberg H.,
RA   Jureka A.S., Obernier K., Guo J.Z., Batra J., Kaake R.M., Weckstein A.R.,
RA   Owens T.W., Gupta M., Pourmal S., Titus E.W., Cakir M., Soucheray M.,
RA   McGregor M., Cakir Z., Jang G., O'Meara M.J., Tummino T.A., Zhang Z.,
RA   Foussard H., Rojc A., Zhou Y., Kuchenov D., Huettenhain R., Xu J.,
RA   Eckhardt M., Swaney D.L., Fabius J.M., Ummadi M., Tutuncuoglu B.,
RA   Rathore U., Modak M., Haas P., Haas K.M., Naing Z.Z.C., Pulido E.H.,
RA   Shi Y., Barrio-Hernandez I., Memon D., Petsalaki E., Dunham A.,
RA   Marrero M.C., Burke D., Koh C., Vallet T., Silvas J.A., Azumaya C.M.,
RA   Billesboelle C., Brilot A.F., Campbell M.G., Diallo A., Dickinson M.S.,
RA   Diwanji D., Herrera N., Hoppe N., Kratochvil H.T., Liu Y., Merz G.E.,
RA   Moritz M., Nguyen H.C., Nowotny C., Puchades C., Rizo A.N.,
RA   Schulze-Gahmen U., Smith A.M., Sun M., Young I.D., Zhao J., Asarnow D.,
RA   Biel J., Bowen A., Braxton J.R., Chen J., Chio C.M., Chio U.S.,
RA   Deshpande I., Doan L., Faust B., Flores S., Jin M., Kim K., Lam V.L.,
RA   Li F., Li J., Li Y.L., Li Y., Liu X., Lo M., Lopez K.E., Melo A.A.,
RA   Moss F.R. III, Nguyen P., Paulino J., Pawar K.I., Peters J.K.,
RA   Pospiech T.H. Jr., Safari M., Sangwan S., Schaefer K., Thomas P.V.,
RA   Thwin A.C., Trenker R., Tse E., Tsui T.K.M., Wang F., Whitis N., Yu Z.,
RA   Zhang K., Zhang Y., Zhou F., Saltzberg D., Hodder A.J., Shun-Shion A.S.,
RA   Williams D.M., White K.M., Rosales R., Kehrer T., Miorin L., Moreno E.,
RA   Patel A.H., Rihn S., Khalid M.M., Vallejo-Gracia A., Fozouni P.,
RA   Simoneau C.R., Roth T.L., Wu D., Karim M.A., Ghoussaini M., Dunham I.,
RA   Berardi F., Weigang S., Chazal M., Park J., Logue J., McGrath M.,
RA   Weston S., Haupt R., Hastie C.J., Elliott M., Brown F., Burness K.A.,
RA   Reid E., Dorward M., Johnson C., Wilkinson S.G., Geyer A., Giesel D.M.,
RA   Baillie C., Raggett S., Leech H., Toth R., Goodman N., Keough K.C.,
RA   Lind A.L., Klesh R.J., Hemphill K.R., Carlson-Stevermer J., Oki J.,
RA   Holden K., Maures T., Pollard K.S., Sali A., Agard D.A., Cheng Y.,
RA   Fraser J.S., Frost A., Jura N., Kortemme T., Manglik A., Southworth D.R.,
RA   Stroud R.M., Alessi D.R., Davies P., Frieman M.B., Ideker T., Abate C.,
RA   Jouvenet N., Kochs G., Shoichet B., Ott M., Palmarini M., Shokat K.M.,
RA   Garcia-Sastre A., Rassen J.A., Grosse R., Rosenberg O.S., Verba K.A.,
RA   Basler C.F., Vignuzzi M., Peden A.A., Beltrao P., Krogan N.J.;
RT   "Comparative host-coronavirus protein interaction networks reveal pan-viral
RT   disease mechanisms.";
RL   Science 0:0-0(2020).
RN   [3]
RP   FUNCTION.
RX   PubMed=33157038; DOI=10.1016/j.cell.2020.10.039;
RA   Ghosh S., Dellibovi-Ragheb T.A., Kerviel A., Pak E., Qiu Q., Fisher M.,
RA   Takvorian P.M., Bleck C., Hsu V.W., Fehr A.R., Perlman S., Achar S.R.,
RA   Straus M.R., Whittaker G.R., de Haan C.A.M., Kehrl J., Altan-Bonnet G.,
RA   Altan-Bonnet N.;
RT   "beta-Coronaviruses Use Lysosomes for Egress Instead of the Biosynthetic
RT   Secretory Pathway.";
RL   Cell 183:1520-1535(2020).
RN   [4]
RP   FUNCTION, INTERACTION WITH HOST VPS39, AND SUBCELLULAR LOCATION.
RX   PubMed=33422265; DOI=10.1016/j.devcel.2020.12.010;
RA   Miao G., Zhao H., Li Y., Ji M., Chen Y., Shi Y., Bi Y., Wang P., Zhang H.;
RT   "ORF3a of the COVID-19 virus SARS-CoV-2 blocks HOPS complex-mediated
RT   assembly of the SNARE complex required for autolysosome formation.";
RL   Dev. Cell 56:427-442(2020).
RN   [5]
RP   FUNCTION, INTERACTION WITH HOST HMGB1 AND HOST HMOX1, AND SUBCELLULAR
RP   LOCATION.
RX   PubMed=35239449; DOI=10.1080/15548627.2022.2039992;
RA   Zhang X., Yang Z., Pan T., Long X., Sun Q., Wang P.H., Li X., Kuang E.;
RT   "SARS-CoV-2 ORF3a induces RETREG1/FAM134B-dependent reticulophagy and
RT   triggers sequential ER stress and inflammatory responses during SARS-CoV-2
RT   infection.";
RL   Autophagy 0:0-0(2022).
RN   [6]
RP   DISORDERED REGIONS.
RX   PubMed=35108439; DOI=10.1111/febs.16379;
RA   Quaglia F., Salladini E., Carraro M., Minervini G., Tosatto S.C.E.,
RA   Le Mercier P.;
RT   "SARS-CoV-2 variants preferentially emerge at intrinsically disordered
RT   protein sites helping immune evasion.";
RL   FEBS J. 289:4240-4250(2022).
RN   [7]
RP   STRUCTURE BY ELECTRON MICROSCOPY (2.1 ANGSTROMS), FUNCTION, SUBUNIT,
RP   MUTAGENESIS OF 1-MET--LEU-41; 57-GLN-SER-58; GLN-57 AND GLN-116, AND
RP   SUBCELLULAR LOCATION.
RX   PubMed=34158638; DOI=10.1038/s41594-021-00619-0;
RA   Kern D.M., Sorum B., Mali S.S., Hoel C.M., Sridharan S., Remis J.P.,
RA   Toso D.B., Kotecha A., Bautista D.M., Brohawn S.G.;
RT   "Cryo-EM structure of SARS-CoV-2 ORF3a in lipid nanodiscs.";
RL   Nat. Struct. Mol. Biol. 28:573-582(2021).
CC   -!- FUNCTION: Plays a role in viral egress via lysosomal trafficking
CC       (PubMed:33157038, PubMed:33422265). Forms homotetrameric ion channels
CC       (viroporins) localized at endosomes and lysosomes, that may induce
CC       deacidification of lysosomes, allowing safe egress of virions via
CC       lysosomal trafficking (PubMed:33157038, PubMed:33422265,
CC       PubMed:34158638). Also blocks autolysosome formation by binding and
CC       sequestering the host component VPS39 for homotypic fusion and protein
CC       sorting (HOPS) on late endosomes (PubMed:33422265). This prevents
CC       fusion of autophagosomes with lysosomes, disrupting autophagy and
CC       facilitating virus egress (PubMed:33422265). Induces host
CC       RETREG1/FAM134B-dependent reticulophagy by interacting with host HMGB1
CC       and enhancing the association between HMGB1 and host BECN1
CC       (PubMed:35239449). This induces endoplasmic reticulum stress and
CC       inflammatory responses and facilitates viral infection
CC       (PubMed:35239449). {ECO:0000269|PubMed:33157038,
CC       ECO:0000269|PubMed:33422265, ECO:0000269|PubMed:34158638,
CC       ECO:0000269|PubMed:35239449}.
CC   -!- SUBUNIT: Homodimer (PubMed:34158638), a subset forms homotetramer of
CC       two homodimers linked non covalently (PubMed:34158638,
CC       PubMed:34158638). Interacts with M, S and E proteins. Also interacts
CC       with the accessory protein 7a (By similarity). Interacts with host
CC       VPS39, sequestering it on late endosomes (PubMed:33422265). Interacts
CC       with host HMGB1; the interaction enhances the association between HMGB1
CC       and host BECN1, promoting reticulophagy (PubMed:35239449). Interacts
CC       with HMOX1; the interaction promotes ORF3A-induced autophagy but is
CC       unlikely to be involved in ORF3A-mediated induction of reticulophagy
CC       (PubMed:35239449). {ECO:0000250|UniProtKB:P59632,
CC       ECO:0000269|PubMed:33422265, ECO:0000269|PubMed:34158638,
CC       ECO:0000269|PubMed:35239449}.
CC   -!- INTERACTION:
CC       P0DTC3; P0DTC3: 3a; NbExp=2; IntAct=EBI-25475894, EBI-25475894;
CC       P0DTC3; Q12846: STX4; Xeno; NbExp=4; IntAct=EBI-25475894, EBI-744942;
CC       P0DTC3; Q9P2Y5: UVRAG; Xeno; NbExp=6; IntAct=EBI-25475894, EBI-2952704;
CC       P0DTC3; P51809: VAMP7; Xeno; NbExp=4; IntAct=EBI-25475894, EBI-1052205;
CC       P0DTC3; Q96JC1: VPS39; Xeno; NbExp=18; IntAct=EBI-25475894, EBI-1050197;
CC       P0DTC3; P49754: VPS41; Xeno; NbExp=4; IntAct=EBI-25475894, EBI-2130459;
CC   -!- SUBCELLULAR LOCATION: Virion {ECO:0000250|UniProtKB:P59632}. Host cell
CC       membrane {ECO:0000250|UniProtKB:P59632, ECO:0000269|PubMed:33060197,
CC       ECO:0000269|PubMed:34158638}; Multi-pass membrane protein
CC       {ECO:0000250|UniProtKB:P59632, ECO:0000269|PubMed:34158638}. Host
CC       endoplasmic reticulum membrane {ECO:0000269|PubMed:35239449}; Multi-
CC       pass membrane protein {ECO:0000269|PubMed:34158638}. Secreted
CC       {ECO:0000250|UniProtKB:P59632}. Host cytoplasm
CC       {ECO:0000250|UniProtKB:P59632, ECO:0000269|PubMed:33060197}. Host
CC       endosome {ECO:0000269|PubMed:33060197, ECO:0000269|PubMed:33422265}.
CC       Host lysosome {ECO:0000269|PubMed:33422265}. Note=The cell surface
CC       expressed protein can undergo endocytosis. The protein is secreted in
CC       association with membranous structures. {ECO:0000250|UniProtKB:P59632}.
CC   -!- DOMAIN: The second or the third transmembrane region are responsible
CC       for Golgi localization. {ECO:0000250|UniProtKB:P59632}.
CC   -!- PTM: Exists in both O-glycosylated and non-glycosylated forms. The
CC       glycosylated form is associated with the virion.
CC       {ECO:0000250|UniProtKB:P59632}.
CC   -!- POLYMORPHISM: Variant Omicron/BA.1 and BA.2 belong to a lineage first
CC       isolated in South Africa (November 2021). {ECO:0000305}.
CC   -!- POLYMORPHISM: Variant Omicron/BQ.1.1 belongs to a lineage first
CC       isolated in Nigeria (November 2022). {ECO:0000305}.
CC   -!- POLYMORPHISM: Variant Omicron/XBB.1.5 belongs to a lineage first
CC       isolated in United States (November 2022). It is the result of
CC       recombination between omicron BJ.1 and BM.1.1. Moreover XBB.1.5 do not
CC       express ORF8. {ECO:0000305}.
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DR   EMBL; MN908947; QHD43417.1; -; Genomic_RNA.
DR   PDB; 6XDC; EM; 2.90 A; A/B=1-275.
DR   PDB; 7KJR; EM; 2.08 A; A/B=1-275.
DR   PDB; 8EQJ; EM; 3.00 A; A/B=1-275.
DR   PDB; 8EQT; EM; 3.40 A; A/B=1-275.
DR   PDB; 8EQU; EM; 2.80 A; A/B=1-275.
DR   PDBsum; 6XDC; -.
DR   PDBsum; 7KJR; -.
DR   PDBsum; 8EQJ; -.
DR   PDBsum; 8EQT; -.
DR   PDBsum; 8EQU; -.
DR   SMR; P0DTC3; -.
DR   BioGRID; 4383868; 1179.
DR   ComplexPortal; CPX-6098; SARS-CoV-2 3a complex.
DR   IntAct; P0DTC3; 445.
DR   TCDB; 1.A.57.1.5; the human sars coronavirus viroporin (sars-vp) family.
DR   GlyGen; P0DTC3; 2 sites.
DR   iPTMnet; P0DTC3; -.
DR   DNASU; 43740569; -.
DR   KEGG; vg:43740569; -.
DR   Reactome; R-HSA-9694322; Virion Assembly and Release.
DR   Reactome; R-HSA-9694614; Attachment and Entry.
DR   Reactome; R-HSA-9694635; Translation of Structural Proteins.
DR   Reactome; R-HSA-9694719; Maturation of protein 3a.
DR   Reactome; R-HSA-9705671; SARS-CoV-2 activates/modulates innate and adaptive immune responses.
DR   Reactome; R-HSA-9733458; Induction of Cell-Cell Fusion.
DR   Reactome; R-HSA-9754560; SARS-CoV-2 modulates autophagy.
DR   Reactome; R-HSA-9755779; SARS-CoV-2 targets host intracellular signalling and regulatory pathways.
DR   PRO; PR:P0DTC3; -.
DR   Proteomes; UP000464024; Genome.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0044165; C:host cell endoplasmic reticulum; IDA:UniProtKB.
DR   GO; GO:0044167; C:host cell endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0044174; C:host cell endosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0044187; C:host cell lysosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR   GO; GO:0055036; C:virion membrane; TAS:Reactome.
DR   GO; GO:0005891; C:voltage-gated calcium channel complex; IPI:ComplexPortal.
DR   GO; GO:0008076; C:voltage-gated potassium channel complex; IPI:ComplexPortal.
DR   GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR   GO; GO:0140677; F:molecular function activator activity; IMP:DisProt.
DR   GO; GO:0005216; F:monoatomic ion channel activity; IEA:UniProtKB-KW.
DR   GO; GO:0140883; P:induction by virus of host reticulophagy; IDA:UniProtKB.
DR   GO; GO:0098662; P:inorganic cation transmembrane transport; IDA:ComplexPortal.
DR   GO; GO:0039707; P:pore formation by virus in membrane of host cell; IEA:UniProtKB-KW.
DR   GO; GO:0051259; P:protein complex oligomerization; IEA:UniProtKB-KW.
DR   CDD; cd21648; SARS-CoV-like_ORF3a; 1.
DR   DisProt; DP03003; -.
DR   InterPro; IPR046446; a/bCoV_VIROPORIN_3A-like_CD.
DR   InterPro; IPR046445; a/bCoV_VIROPORIN_3A-like_TM.
DR   InterPro; IPR024407; Protein_3a_bCoV.
DR   Pfam; PF11289; bCoV_viroporin; 1.
DR   PROSITE; PS51967; COV_VIROPORIN_3A_CD; 1.
DR   PROSITE; PS51966; COV_VIROPORIN_3A_TM; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Activation of host autophagy by virus; Glycoprotein;
KW   Host cell membrane; Host cytoplasm; Host endoplasmic reticulum;
KW   Host endosome; Host lysosome; Host membrane; Host-virus interaction;
KW   Ion channel; Ion transport; Membrane; Reference proteome; Secreted;
KW   Transmembrane; Transmembrane helix; Transport; Viral ion channel; Virion.
FT   CHAIN           1..275
FT                   /note="ORF3a protein"
FT                   /id="PRO_0000449650"
FT   TOPO_DOM        1..42
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000269|PubMed:34158638"
FT   TRANSMEM        43..61
FT                   /note="Helical"
FT                   /evidence="ECO:0000269|PubMed:34158638"
FT   TOPO_DOM        62..67
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000269|PubMed:34158638"
FT   TRANSMEM        68..93
FT                   /note="Helical"
FT                   /evidence="ECO:0000269|PubMed:34158638"
FT   TOPO_DOM        94..101
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000269|PubMed:34158638"
FT   TRANSMEM        102..126
FT                   /note="Helical"
FT                   /evidence="ECO:0000269|PubMed:34158638"
FT   TOPO_DOM        127..275
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000269|PubMed:34158638"
FT   DOMAIN          33..141
FT                   /note="CoV 3a-like viroporin TM"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01311"
FT   DOMAIN          145..237
FT                   /note="CoV 3a-like viroporin CD"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01312"
FT   REGION          1..39
FT                   /note="Disordered"
FT                   /evidence="ECO:0000305|PubMed:35108439"
FT   REGION          239..275
FT                   /note="Disordered"
FT                   /evidence="ECO:0000305|PubMed:35108439"
FT   SITE            133
FT                   /note="Involved in polymerization"
FT                   /evidence="ECO:0000250|UniProtKB:P59632"
FT   CARBOHYD        32
FT                   /note="O-linked (GalNAc...) threonine; by host"
FT                   /evidence="ECO:0000250|UniProtKB:P59632"
FT   CARBOHYD        34
FT                   /note="O-linked (GalNAc...) threonine; by host"
FT                   /evidence="ECO:0000255"
FT   VARIANT         26
FT                   /note="S -> L (in strain: Delta/B.1.617.2 and Kappa/
FT                   B.1.617.1)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         42
FT                   /note="P -> L (in strain: Iota/B.1.526)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         57
FT                   /note="Q -> H (in strain: Beta/B.1.351, Epsilon/B.1.429,
FT                   Iota/B.1.526 and Mu/B.1.621)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         171
FT                   /note="S -> L (in strain: Beta/B.1.351)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         223
FT                   /note="T -> I (in strain: Omicron/BA.2, Omicron/BA.2.12.1,
FT                   Omicron/BA.2.75, Omicron/BA.4, Omicron/BA.5, Omicron/
FT                   BQ.1.1, Omicron/XBB.1.5)"
FT   VARIANT         253
FT                   /note="S -> P (in strain: Gamma/P.1)"
FT                   /evidence="ECO:0000305"
FT   VARIANT         257
FT                   /note="Missing (in strain: Mu/B.1.621)"
FT                   /evidence="ECO:0000305"
FT   MUTAGEN         1..41
FT                   /note="Missing: Partial loss of Ca(2+) and NMDG(+)
FT                   permeability. Increased localization at host plasma
FT                   membrane."
FT                   /evidence="ECO:0000269|PubMed:34158638"
FT   MUTAGEN         57..58
FT                   /note="QS->EL: Partial loss of Ca(2+) and NMDG(+)
FT                   permeability."
FT                   /evidence="ECO:0000269|PubMed:34158638"
FT   MUTAGEN         57
FT                   /note="Q->H: No effect on ion permeability."
FT                   /evidence="ECO:0000269|PubMed:34158638"
FT   MUTAGEN         116
FT                   /note="Q->L: Partial loss of Ca(2+) and NMDG(+)
FT                   permeability."
FT                   /evidence="ECO:0000269|PubMed:34158638"
FT   HELIX           44..60
FT                   /evidence="ECO:0007829|PDB:7KJR"
FT   HELIX           68..99
FT                   /evidence="ECO:0007829|PDB:7KJR"
FT   HELIX           103..105
FT                   /evidence="ECO:0007829|PDB:7KJR"
FT   HELIX           106..133
FT                   /evidence="ECO:0007829|PDB:7KJR"
FT   HELIX           137..140
FT                   /evidence="ECO:0007829|PDB:7KJR"
FT   STRAND          144..150
FT                   /evidence="ECO:0007829|PDB:7KJR"
FT   STRAND          155..160
FT                   /evidence="ECO:0007829|PDB:7KJR"
FT   STRAND          165..172
FT                   /evidence="ECO:0007829|PDB:7KJR"
FT   STRAND          183..186
FT                   /evidence="ECO:0007829|PDB:7KJR"
FT   STRAND          189..192
FT                   /evidence="ECO:0007829|PDB:7KJR"
FT   STRAND          199..204
FT                   /evidence="ECO:0007829|PDB:7KJR"
FT   STRAND          209..218
FT                   /evidence="ECO:0007829|PDB:7KJR"
FT   HELIX           220..223
FT                   /evidence="ECO:0007829|PDB:7KJR"
FT   STRAND          228..235
FT                   /evidence="ECO:0007829|PDB:7KJR"
SQ   SEQUENCE   275 AA;  31123 MW;  4688E6D477E031C4 CRC64;
     MDLFMRIFTI GTVTLKQGEI KDATPSDFVR ATATIPIQAS LPFGWLIVGV ALLAVFQSAS
     KIITLKKRWQ LALSKGVHFV CNLLLLFVTV YSHLLLVAAG LEAPFLYLYA LVYFLQSINF
     VRIIMRLWLC WKCRSKNPLL YDANYFLCWH TNCYDYCIPY NSVTSSIVIT SGDGTTSPIS
     EHDYQIGGYT EKWESGVKDC VVLHSYFTSD YYQLYSTQLS TDTGVEHVTF FIYNKIVDEP
     EEHVQIHTID GSSGVVNPVM EPIYDEPTTT TSVPL
//