ID   R1A_MERS1               Reviewed;        4391 AA.
AC   K9N638;
DT   29-MAY-2013, integrated into UniProtKB/Swiss-Prot.
DT   06-MAR-2013, sequence version 1.
DT   27-MAR-2024, entry version 64.
DE   RecName: Full=Replicase polyprotein 1a;
DE            Short=pp1a;
DE   AltName: Full=ORF1a polyprotein;
DE   Contains:
DE     RecName: Full=Host translation inhibitor nsp1;
DE              Short=nsp1;
DE     AltName: Full=Leader protein;
DE   Contains:
DE     RecName: Full=Non-structural protein 2;
DE              Short=nsp2;
DE     AltName: Full=p65 homolog;
DE   Contains:
DE     RecName: Full=Papain-like protease nsp3;
DE              Short=PL-PRO;
DE              EC=3.4.19.12;
DE              EC=3.4.22.-;
DE     AltName: Full=Non-structural protein 3;
DE              Short=nsp3;
DE     AltName: Full=PL2-PRO;
DE   Contains:
DE     RecName: Full=Non-structural protein 4;
DE              Short=nsp4;
DE   Contains:
DE     RecName: Full=3C-like proteinase nsp5;
DE              Short=3CL-PRO;
DE              Short=3CLp;
DE              EC=3.4.22.69;
DE     AltName: Full=nsp5;
DE   Contains:
DE     RecName: Full=Non-structural protein 6;
DE              Short=nsp6;
DE   Contains:
DE     RecName: Full=Non-structural protein 7;
DE              Short=nsp7;
DE   Contains:
DE     RecName: Full=Non-structural protein 8;
DE              Short=nsp8;
DE   Contains:
DE     RecName: Full=RNA-capping enzyme subunit nsp9;
DE     AltName: Full=Non-structural protein 9;
DE              Short=nsp9;
DE              EC=2.7.7.50;
DE   Contains:
DE     RecName: Full=Non-structural protein 10;
DE              Short=nsp10;
DE     AltName: Full=Growth factor-like peptide;
DE              Short=GFL;
DE   Contains:
DE     RecName: Full=Non-structural protein 11;
DE              Short=nsp11;
GN   ORFNames=1a;
OS   Middle East respiratory syndrome-related coronavirus (isolate United
OS   Kingdom/H123990006/2012) (MERS-CoV) (Betacoronavirus England 1).
OC   Viruses; Riboviria; Orthornavirae; Pisuviricota; Pisoniviricetes;
OC   Nidovirales; Cornidovirineae; Coronaviridae; Orthocoronavirinae;
OC   Betacoronavirus; Merbecovirus;
OC   Middle East respiratory syndrome-related coronavirus.
OX   NCBI_TaxID=1263720;
OH   NCBI_TaxID=9838; Camelus dromedarius (Dromedary) (Arabian camel).
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RA   Nishi O., Iiyama K., Yasunaga-Aoki C., Shimizu S.;
RT   "The phylogenetic status and pathogenicity of a new isolate of Metarhizium
RT   sp. from a fruit beetle larvae in Japan.";
RL   Submitted (NOV-2012) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   FUNCTION (PAPAIN-LIKE PROTEINASE).
RX   PubMed=25142582; DOI=10.1128/jvi.01294-14;
RA   Baez-Santos Y.M., Mielech A.M., Deng X., Baker S., Mesecar A.D.;
RT   "Catalytic function and substrate specificity of the papain-like protease
RT   domain of nsp3 from the Middle East respiratory syndrome coronavirus.";
RL   J. Virol. 88:12511-12527(2014).
RN   [3]
RP   FUNCTION (NSP1).
RX   PubMed=26311885; DOI=10.1128/jvi.01352-15;
RA   Lokugamage K.G., Narayanan K., Nakagawa K., Terasaki K., Ramirez S.I.,
RA   Tseng C.T., Makino S.;
RT   "Middle east respiratory syndrome coronavirus nsp1 inhibits host gene
RT   expression by selectively targeting mRNAs transcribed in the nucleus while
RT   sparing mRNAs of cytoplasmic origin.";
RL   J. Virol. 89:10970-10981(2015).
CC   -!- FUNCTION: The replicase polyprotein of coronaviruses is a
CC       multifunctional protein: it contains the activities necessary for the
CC       transcription of negative stranded RNA, leader RNA, subgenomic mRNAs
CC       and progeny virion RNA as well as proteinases responsible for the
CC       cleavage of the polyprotein into functional products.
CC       {ECO:0000250|UniProtKB:P0C6X7}.
CC   -!- FUNCTION: [Host translation inhibitor nsp1]: Promotes the degradation
CC       of host mRNAs by inducing an endonucleolytic RNA cleavage in template
CC       mRNAs, and inhibits of host mRNA translation, a function that is
CC       separable from its RNA cleavage activity. By suppressing host gene
CC       expression, nsp1 facilitates efficient viral gene expression in
CC       infected cells and evasion from host immune response.
CC       {ECO:0000269|PubMed:26311885}.
CC   -!- FUNCTION: [Non-structural protein 2]: May play a role in the modulation
CC       of host cell survival signaling pathway by interacting with host PHB
CC       and PHB2. Indeed, these two proteins play a role in maintaining the
CC       functional integrity of the mitochondria and protecting cells from
CC       various stresses. {ECO:0000250|UniProtKB:P0C6X7}.
CC   -!- FUNCTION: [Papain-like protease nsp3]: Responsible for the cleavages
CC       located at the N-terminus of the replicase polyprotein. In addition,
CC       PL-PRO possesses a deubiquitinating/deISGylating activity and processes
CC       both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular
CC       substrates. Participates, together with nsp4, in the assembly of
CC       virally induced cytoplasmic double-membrane vesicles necessary for
CC       viral replication. Antagonizes innate immune induction of type I
CC       interferon by blocking the phosphorylation, dimerization and subsequent
CC       nuclear translocation of host IRF3. Prevents also host NF-kappa-B.
CC       signaling. {ECO:0000250|UniProtKB:P0C6X7, ECO:0000269|PubMed:25142582}.
CC   -!- FUNCTION: [Non-structural protein 4]: Participates in the assembly of
CC       virally-induced cytoplasmic double-membrane vesicles necessary for
CC       viral replication. {ECO:0000250|UniProtKB:P0C6X7}.
CC   -!- FUNCTION: [3C-like proteinase nsp5]: Cleaves the C-terminus of
CC       replicase polyprotein at 11 sites. Recognizes substrates containing the
CC       core sequence [ILMVF]-Q-|-[SGACN]. Also able to bind an ADP-ribose-1''-
CC       phosphate (ADRP). {ECO:0000250|UniProtKB:P0C6X7, ECO:0000255|PROSITE-
CC       ProRule:PRU00772}.
CC   -!- FUNCTION: [Non-structural protein 6]: Plays a role in the initial
CC       induction of autophagosomes from host reticulum endoplasmic. Later,
CC       limits the expansion of these phagosomes that are no longer able to
CC       deliver viral components to lysosomes. {ECO:0000250|UniProtKB:P0C6X7}.
CC   -!- FUNCTION: [Non-structural protein 7]: Forms a hexadecamer with nsp8 (8
CC       subunits of each) that may participate in viral replication by acting
CC       as a primase. Alternatively, may synthesize substantially longer
CC       products than oligonucleotide primers. {ECO:0000250|UniProtKB:P0C6X7}.
CC   -!- FUNCTION: [Non-structural protein 8]: Forms a hexadecamer with nsp7 (8
CC       subunits of each) that may participate in viral replication by acting
CC       as a primase. Alternatively, may synthesize substantially longer
CC       products than oligonucleotide primers. {ECO:0000250|UniProtKB:P0C6X7}.
CC   -!- FUNCTION: [RNA-capping enzyme subunit nsp9]: Catalytic subunit of viral
CC       RNA capping enzyme which catalyzes the RNA guanylyltransferase reaction
CC       for genomic and sub-genomic RNAs. The kinase-like NiRAN domain of NSP12
CC       transfers RNA to the amino terminus of NSP9, forming a covalent RNA-
CC       protein intermediate. Subsequently, the NiRAN domain transfers RNA to
CC       GDP, forming the core cap structure GpppA-RNA. The NSP14 and NSP16
CC       methyltransferases then add methyl groups to form functional cap
CC       structures. {ECO:0000250|UniProtKB:P0DTC1}.
CC   -!- FUNCTION: [Non-structural protein 10]: Plays a pivotal role in viral
CC       transcription by stimulating both nsp14 3'-5' exoribonuclease and nsp16
CC       2'-O-methyltransferase activities. Therefore plays an essential role in
CC       viral mRNAs cap methylation. {ECO:0000250|UniProtKB:P0C6X7}.
CC   -!- CATALYTIC ACTIVITY: [Papain-like protease nsp3]:
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:0000250|UniProtKB:P0DTC1};
CC   -!- CATALYTIC ACTIVITY: [3C-like proteinase nsp5]:
CC       Reaction=TSAVLQ-|-SGFRK-NH2 and SGVTFQ-|-GKFKK the two peptides
CC         corresponding to the two self-cleavage sites of the SARS 3C-like
CC         proteinase are the two most reactive peptide substrates. The enzyme
CC         exhibits a strong preference for substrates containing Gln at P1
CC         position and Leu at P2 position.; EC=3.4.22.69;
CC         Evidence={ECO:0000250|UniProtKB:P0DTC1};
CC   -!- CATALYTIC ACTIVITY: [RNA-capping enzyme subunit nsp9]:
CC       Reaction=a 5'-end diphospho-ribonucleoside in mRNA + GTP + H(+) = a 5'-
CC         end (5'-triphosphoguanosine)-(ribonucleoside) in mRNA + diphosphate;
CC         Xref=Rhea:RHEA:67012, Rhea:RHEA-COMP:17165, Rhea:RHEA-COMP:17166,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, ChEBI:CHEBI:37565,
CC         ChEBI:CHEBI:167616, ChEBI:CHEBI:167617; EC=2.7.7.50;
CC         Evidence={ECO:0000250|UniProtKB:P0DTC1};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:67014;
CC         Evidence={ECO:0000250|UniProtKB:P0DTC1};
CC   -!- SUBUNIT: Nsp2 interacts with host PHB and PHB2. 3CL-PRO exists as
CC       monomer and homodimer. Nsp4 interacts with PL-PRO and nsp6. Only the
CC       homodimer shows catalytic activity. Eight copies of nsp7 and eight
CC       copies of nsp8 assemble to form a heterohexadecamer dsRNA-encircling
CC       ring structure. Nsp9 is a dimer. {ECO:0000250|UniProtKB:P0C6X7}.
CC   -!- INTERACTION:
CC       K9N638; PRO_0000037312 [P0C6X7]: rep; Xeno; NbExp=2; IntAct=EBI-25618448, EBI-25487250;
CC       PRO_0000422456; Q64339: Isg15; Xeno; NbExp=2; IntAct=EBI-25635184, EBI-8345781;
CC       PRO_0000422460; PRO_0000422461 [K9N638]: 1a; NbExp=2; IntAct=EBI-26366263, EBI-26366276;
CC   -!- SUBCELLULAR LOCATION: [Papain-like protease nsp3]: Host membrane;
CC       Multi-pass membrane protein. Host cytoplasm
CC       {ECO:0000250|UniProtKB:P0C6X7}.
CC   -!- SUBCELLULAR LOCATION: [Non-structural protein 4]: Host membrane; Multi-
CC       pass membrane protein. Host cytoplasm. Note=Localizes in virally-
CC       induced cytoplasmic double-membrane vesicles.
CC       {ECO:0000250|UniProtKB:P0C6X7}.
CC   -!- SUBCELLULAR LOCATION: [Non-structural protein 6]: Host membrane
CC       {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}.
CC   -!- SUBCELLULAR LOCATION: [Non-structural protein 7]: Host cytoplasm, host
CC       perinuclear region {ECO:0000250}. Note=nsp7, nsp8, nsp9 and nsp10 are
CC       localized in cytoplasmic foci, largely perinuclear. Late in infection,
CC       they merge into confluent complexes (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: [Non-structural protein 8]: Host cytoplasm, host
CC       perinuclear region {ECO:0000250}. Note=nsp7, nsp8, nsp9 and nsp10 are
CC       localized in cytoplasmic foci, largely perinuclear. Late in infection,
CC       they merge into confluent complexes (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: [RNA-capping enzyme subunit nsp9]: Host
CC       cytoplasm, host perinuclear region {ECO:0000250}. Note=nsp7, nsp8, nsp9
CC       and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late
CC       in infection, they merge into confluent complexes (By similarity).
CC       {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: [Non-structural protein 10]: Host cytoplasm, host
CC       perinuclear region {ECO:0000250}. Note=nsp7, nsp8, nsp9 and nsp10 are
CC       localized in cytoplasmic foci, largely perinuclear. Late in infection,
CC       they merge into confluent complexes (By similarity). {ECO:0000250}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Ribosomal frameshifting; Named isoforms=2;
CC       Name=Replicase polyprotein 1a; Synonyms=pp1a, ORF1a polyprotein;
CC         IsoId=K9N638-1; Sequence=Displayed;
CC       Name=Replicase polyprotein 1ab; Synonyms=pp1ab;
CC         IsoId=K9N7C7-1; Sequence=External;
CC   -!- DOMAIN: The hydrophobic domains (HD) could mediate the membrane
CC       association of the replication complex and thereby alter the
CC       architecture of the host cell membrane.
CC   -!- PTM: Specific enzymatic cleavages in vivo by its own proteases yield
CC       mature proteins. 3CL-PRO and PL-PRO proteinases are autocatalytically
CC       processed (By similarity). {ECO:0000250}.
CC   -!- MISCELLANEOUS: [Isoform Replicase polyprotein 1a]: Produced by
CC       conventional translation.
CC   -!- SIMILARITY: Belongs to the coronaviruses polyprotein 1ab family.
CC       {ECO:0000305}.
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DR   EMBL; KC164505; AFY13305.1; -; Genomic_RNA.
DR   PDB; 4R3D; X-ray; 2.82 A; A/B=1481-1811.
DR   PDB; 5DUS; X-ray; 1.43 A; A=1110-1273.
DR   PDB; 5HIH; X-ray; 1.66 A; A=1109-1275.
DR   PDB; 5WKJ; X-ray; 2.05 A; A=3248-3553.
DR   PDB; 5WKK; X-ray; 1.55 A; A=3248-3553.
DR   PDB; 5WKL; X-ray; 1.85 A; A=3248-3553.
DR   PDB; 5WKM; X-ray; 2.25 A; A=3248-3553.
DR   PDB; 7T3Y; X-ray; 1.90 A; A/B=3248-3553.
DR   PDB; 7T3Z; X-ray; 1.95 A; A/B=3248-3553.
DR   PDB; 7T40; X-ray; 1.70 A; A=3248-3553.
DR   PDB; 7T41; X-ray; 2.10 A; A=3248-3553.
DR   PDB; 8R5J; X-ray; 1.90 A; A/B=3248-3553.
DR   PDBsum; 4R3D; -.
DR   PDBsum; 5DUS; -.
DR   PDBsum; 5HIH; -.
DR   PDBsum; 5WKJ; -.
DR   PDBsum; 5WKK; -.
DR   PDBsum; 5WKL; -.
DR   PDBsum; 5WKM; -.
DR   PDBsum; 7T3Y; -.
DR   PDBsum; 7T3Z; -.
DR   PDBsum; 7T40; -.
DR   PDBsum; 7T41; -.
DR   PDBsum; 8R5J; -.
DR   SMR; K9N638; -.
DR   BioGRID; 4383912; 1.
DR   IntAct; K9N638; 9.
DR   DrugBank; DB15797; GC-373.
DR   DrugBank; DB15796; GC-376 free acid.
DR   SABIO-RK; K9N638; -.
DR   Proteomes; UP000139997; Genome.
DR   GO; GO:0033644; C:host cell membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0044220; C:host cell perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR   GO; GO:0004843; F:cysteine-type deubiquitinase activity; IEA:UniProtKB-EC.
DR   GO; GO:0004197; F:cysteine-type endopeptidase activity; IEA:InterPro.
DR   GO; GO:0004519; F:endonuclease activity; IEA:UniProtKB-KW.
DR   GO; GO:0002151; F:G-quadruplex RNA binding; IEA:InterPro.
DR   GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR   GO; GO:0008242; F:omega peptidase activity; IEA:InterPro.
DR   GO; GO:0003727; F:single-stranded RNA binding; IEA:InterPro.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR   GO; GO:0039595; P:induction by virus of catabolism of host mRNA; IEA:UniProtKB-KW.
DR   GO; GO:0039520; P:induction by virus of host autophagy; IEA:UniProtKB-KW.
DR   GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR   GO; GO:0039648; P:modulation by symbiont of host protein ubiquitination; IEA:UniProtKB-KW.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   GO; GO:0039657; P:suppression by virus of host gene expression; IEA:UniProtKB-KW.
DR   GO; GO:0039579; P:suppression by virus of host ISG15-protein conjugation; IEA:UniProtKB-KW.
DR   GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW.
DR   GO; GO:0039548; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of IRF3 activity; IEA:UniProtKB-KW.
DR   GO; GO:0019079; P:viral genome replication; IEA:InterPro.
DR   GO; GO:0019082; P:viral protein processing; IEA:InterPro.
DR   CDD; cd21901; alpha_betaCoV_Nsp10; 1.
DR   CDD; cd21560; betaCoV-Nsp6; 1.
DR   CDD; cd21517; betaCoV_Nsp2_MERS-like; 1.
DR   CDD; cd21666; betaCoV_Nsp5_Mpro; 1.
DR   CDD; cd21827; betaCoV_Nsp7; 1.
DR   CDD; cd21831; betaCoV_Nsp8; 1.
DR   CDD; cd21898; betaCoV_Nsp9; 1.
DR   CDD; cd21732; betaCoV_PLPro; 1.
DR   CDD; cd21473; cv_Nsp4_TM; 1.
DR   CDD; cd21563; Macro_cv_SUD-M_Nsp3-like; 1.
DR   CDD; cd21557; Macro_X_Nsp3-like; 1.
DR   CDD; cd21878; MERS-CoV-like_Nsp1; 1.
DR   CDD; cd21815; MERS-CoV-like_Nsp3_betaSM; 1.
DR   CDD; cd21823; MERS-CoV-like_Nsp3_NAB; 1.
DR   CDD; cd21523; SUD_C_MERS-CoV_Nsp3; 1.
DR   CDD; cd21716; TM_Y_MERS-CoV-like_Nsp3_C; 1.
DR   CDD; cd21467; Ubl1_cv_Nsp3_N-like; 1.
DR   Gene3D; 1.10.8.1190; -; 1.
DR   Gene3D; 2.60.120.1680; -; 1.
DR   Gene3D; 3.10.20.350; -; 1.
DR   Gene3D; 3.10.20.540; -; 1.
DR   Gene3D; 6.10.140.2090; -; 1.
DR   Gene3D; 1.10.150.420; Coronavirus nonstructural protein 4 C-terminus; 1.
DR   Gene3D; 3.40.220.10; Leucine Aminopeptidase, subunit E, domain 1; 1.
DR   Gene3D; 1.10.1840.10; main proteinase (3clpro) structure, domain 3; 1.
DR   Gene3D; 3.40.220.20; Nsp3, SUD-M subdomain; 1.
DR   Gene3D; 1.10.8.370; nsp7 replicase; 1.
DR   Gene3D; 3.30.70.3540; Nsp8 replicase, head domain; 1.
DR   Gene3D; 2.40.10.250; Replicase NSP9; 1.
DR   Gene3D; 3.40.50.11020; Replicase polyprotein, nucleic acid-binding domain; 1.
DR   Gene3D; 2.40.10.10; Trypsin-like serine proteases; 2.
DR   InterPro; IPR046443; a/bCoV_NSP1_glob.
DR   InterPro; IPR046442; bCoV_NSP1_C.
DR   InterPro; IPR043613; CoV_NSP2_C.
DR   InterPro; IPR047573; CoV_NSP2_M.
DR   InterPro; IPR043611; CoV_NSP3_C.
DR   InterPro; IPR047566; CoV_NSP3_Y3.
DR   InterPro; IPR032505; CoV_NSP4_C.
DR   InterPro; IPR043612; CoV_NSP4_N.
DR   InterPro; IPR022733; DPUP_SUD_C_bCoV.
DR   InterPro; IPR002589; Macro_dom.
DR   InterPro; IPR043472; Macro_dom-like.
DR   InterPro; IPR044371; Macro_X_NSP3-like.
DR   InterPro; IPR036333; NSP10_sf_CoV.
DR   InterPro; IPR021590; NSP1_glob_bCoV.
DR   InterPro; IPR044388; NSP2_MERS-like.
DR   InterPro; IPR043615; NSP2_N_CoV.
DR   InterPro; IPR024375; NSP3_bCoV.
DR   InterPro; IPR047567; NSP3_G2M_bCoV.
DR   InterPro; IPR032592; NSP3_NAB_bCoV.
DR   InterPro; IPR042570; NSP3_NAB_bCoV_sf.
DR   InterPro; IPR038400; NSP3_SUD-M_sf_bCoV.
DR   InterPro; IPR044382; NSP3_SUD_C_MERS-CoV.
DR   InterPro; IPR044357; NSP3_Ubl1_dom_CoV.
DR   InterPro; IPR044353; Nsp3_Ubl2_dom_CoV.
DR   InterPro; IPR038083; NSP3A-like.
DR   InterPro; IPR038123; NSP4_C_sf_CoV.
DR   InterPro; IPR044367; NSP6_betaCoV.
DR   InterPro; IPR043610; NSP6_CoV.
DR   InterPro; IPR014828; NSP7_CoV.
DR   InterPro; IPR037204; NSP7_sf_CoV.
DR   InterPro; IPR014829; NSP8_CoV.
DR   InterPro; IPR037230; NSP8_sf_CoV.
DR   InterPro; IPR014822; NSP9_CoV.
DR   InterPro; IPR036499; NSP9_sf_CoV.
DR   InterPro; IPR013016; Peptidase_C16_CoV.
DR   InterPro; IPR008740; Peptidase_C30_CoV.
DR   InterPro; IPR043477; Peptidase_C30_dom3_CoV.
DR   InterPro; IPR009003; Peptidase_S1_PA.
DR   InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR   InterPro; IPR043177; PLpro_N_sf_CoV.
DR   InterPro; IPR043503; PLpro_palm_finger_dom_CoV.
DR   InterPro; IPR043178; PLpro_thumb_sf_CoV.
DR   InterPro; IPR018995; RNA_synth_NSP10_CoV.
DR   Pfam; PF16251; bCoV_NAB; 1.
DR   Pfam; PF11501; bCoV_NSP1; 1.
DR   Pfam; PF11633; bCoV_SUD_M; 1.
DR   Pfam; PF09401; CoV_NSP10; 1.
DR   Pfam; PF19212; CoV_NSP2_C; 1.
DR   Pfam; PF19211; CoV_NSP2_N; 1.
DR   Pfam; PF19218; CoV_NSP3_C; 1.
DR   Pfam; PF16348; CoV_NSP4_C; 1.
DR   Pfam; PF19217; CoV_NSP4_N; 1.
DR   Pfam; PF19213; CoV_NSP6; 1.
DR   Pfam; PF08716; CoV_NSP7; 1.
DR   Pfam; PF08717; CoV_NSP8; 1.
DR   Pfam; PF08710; CoV_NSP9; 1.
DR   Pfam; PF08715; CoV_peptidase; 1.
DR   Pfam; PF01661; Macro; 1.
DR   Pfam; PF05409; Peptidase_C30; 1.
DR   SMART; SM00506; A1pp; 1.
DR   SUPFAM; SSF144246; Coronavirus NSP10-like; 1.
DR   SUPFAM; SSF140367; Coronavirus NSP7-like; 1.
DR   SUPFAM; SSF143076; Coronavirus NSP8-like; 1.
DR   SUPFAM; SSF52949; Macro domain-like; 1.
DR   SUPFAM; SSF159936; NSP3A-like; 1.
DR   SUPFAM; SSF101816; Replicase NSP9; 1.
DR   SUPFAM; SSF50494; Trypsin-like serine proteases; 1.
DR   PROSITE; PS51963; BCOV_NSP1_C; 1.
DR   PROSITE; PS51942; BCOV_NSP3C_C; 1.
DR   PROSITE; PS51941; BCOV_NSP3C_M; 1.
DR   PROSITE; PS51994; BCOV_NSP3E_G2M; 1.
DR   PROSITE; PS51945; BCOV_NSP3E_NAB; 1.
DR   PROSITE; PS51993; COV_3ECTO; 1.
DR   PROSITE; PS51952; COV_EXON_MTASE_COACT; 1.
DR   PROSITE; PS51962; COV_NSP1; 1.
DR   PROSITE; PS51991; COV_NSP2_C; 1.
DR   PROSITE; PS51990; COV_NSP2_M; 1.
DR   PROSITE; PS51989; COV_NSP2_N; 1.
DR   PROSITE; PS51992; COV_NSP3_Y; 1.
DR   PROSITE; PS51943; COV_NSP3A_UBL; 1.
DR   PROSITE; PS51944; COV_NSP3D_UBL; 1.
DR   PROSITE; PS51946; COV_NSP4C; 1.
DR   PROSITE; PS51949; COV_NSP7; 1.
DR   PROSITE; PS51950; COV_NSP8; 1.
DR   PROSITE; PS51951; COV_NSP9_SSRNA_BD; 1.
DR   PROSITE; PS51442; M_PRO; 1.
DR   PROSITE; PS51154; MACRO; 1.
DR   PROSITE; PS51124; PEPTIDASE_C16; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Activation of host autophagy by virus;
KW   Decay of host mRNAs by virus; Disulfide bond; Endonuclease;
KW   Eukaryotic host gene expression shutoff by virus;
KW   Eukaryotic host translation shutoff by virus; Host cytoplasm;
KW   Host gene expression shutoff by virus; Host membrane;
KW   Host mRNA suppression by virus; Host-virus interaction; Hydrolase;
KW   Inhibition of host innate immune response by virus;
KW   Inhibition of host interferon signaling pathway by virus;
KW   Inhibition of host IRF3 by virus; Inhibition of host ISG15 by virus;
KW   Inhibition of host RLR pathway by virus;
KW   Interferon antiviral system evasion; Membrane; Metal-binding;
KW   Methyltransferase;
KW   Modulation of host ubiquitin pathway by viral deubiquitinase;
KW   Modulation of host ubiquitin pathway by virus; Nuclease; Protease;
KW   Reference proteome; Repeat; Ribosomal frameshifting; RNA-binding;
KW   Thiol protease; Transferase; Transmembrane; Transmembrane helix;
KW   Ubl conjugation pathway; Viral immunoevasion; Zinc; Zinc-finger.
FT   CHAIN           1..193
FT                   /note="Host translation inhibitor nsp1"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000422454"
FT   CHAIN           194..853
FT                   /note="Non-structural protein 2"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000422455"
FT   CHAIN           854..2740
FT                   /note="Papain-like protease nsp3"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000422456"
FT   CHAIN           2741..3247
FT                   /note="Non-structural protein 4"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000422457"
FT   CHAIN           3248..3553
FT                   /note="3C-like proteinase nsp5"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000422458"
FT   CHAIN           3554..3845
FT                   /note="Non-structural protein 6"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000422459"
FT   CHAIN           3846..3928
FT                   /note="Non-structural protein 7"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000422460"
FT   CHAIN           3929..4127
FT                   /note="Non-structural protein 8"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000422461"
FT   CHAIN           4128..4237
FT                   /note="RNA-capping enzyme subunit nsp9"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000422462"
FT   CHAIN           4238..4377
FT                   /note="Non-structural protein 10"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000422463"
FT   CHAIN           4378..4391
FT                   /note="Non-structural protein 11"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000422464"
FT   TRANSMEM        2105..2125
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        2177..2197
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        2281..2301
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        2305..2325
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        2330..2350
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        2757..2777
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        3028..3048
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        3062..3082
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        3104..3124
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        3125..3145
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        3559..3579
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        3593..3613
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        3618..3638
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        3664..3684
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        3691..3711
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        3740..3760
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        3765..3785
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          25..149
FT                   /note="CoV Nsp1 globular"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01307"
FT   DOMAIN          165..193
FT                   /note="BetaCoV Nsp1 C-terminal"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01308"
FT   DOMAIN          195..475
FT                   /note="CoV Nsp2 N-terminal"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT   DOMAIN          481..715
FT                   /note="CoV Nsp2 middle"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01334"
FT   DOMAIN          717..853
FT                   /note="CoV Nsp2 C-terminal"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01335"
FT   DOMAIN          857..966
FT                   /note="Ubiquitin-like 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00214"
FT   DOMAIN          1110..1276
FT                   /note="Macro 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00490"
FT   DOMAIN          1278..1404
FT                   /note="Macro 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00490"
FT   DOMAIN          1404..1477
FT                   /note="DPUP"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01289"
FT   DOMAIN          1482..1537
FT                   /note="Ubiquitin-like 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00214"
FT   DOMAIN          1552..1823
FT                   /note="Peptidase C16"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   DOMAIN          1837..1954
FT                   /note="Nucleic acid-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01290"
FT   DOMAIN          1967..2088
FT                   /note="G2M"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01338"
FT   DOMAIN          2214..2280
FT                   /note="3Ecto"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01337"
FT   DOMAIN          2364..2737
FT                   /note="CoV Nsp3 Y"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   DOMAIN          3151..3247
FT                   /note="Nsp4C"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01291"
FT   DOMAIN          3248..3553
FT                   /note="Peptidase C30"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00772"
FT   DOMAIN          3846..3928
FT                   /note="RdRp Nsp7 cofactor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01294"
FT   DOMAIN          3929..4127
FT                   /note="RdRp Nsp8 cofactor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01295"
FT   DOMAIN          4128..4237
FT                   /note="Nsp9 ssRNA-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01296"
FT   DOMAIN          4238..4377
FT                   /note="ExoN/MTase coactivator"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT   ZN_FING         1672..1709
FT                   /note="C4-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   ZN_FING         4311..4327
FT   ZN_FING         4354..4367
FT   REGION          338..359
FT                   /note="C4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT   REGION          383..436
FT                   /note="C2HC"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT   REGION          2040..2363
FT                   /note="HD1"
FT   REGION          2364..2454
FT                   /note="Y1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   REGION          2368..2381
FT                   /note="ZF1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   REGION          2414..2424
FT                   /note="ZF2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   REGION          2455..2737
FT                   /note="CoV-Y"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   REGION          2455..2553
FT                   /note="Y2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   REGION          2554..2636
FT                   /note="Y3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   REGION          2637..2737
FT                   /note="Y4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   REGION          2761..3171
FT                   /note="HD2"
FT   REGION          3571..3785
FT                   /note="HD3"
FT   ACT_SITE        1592
FT                   /note="For PL-PRO activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   ACT_SITE        1759
FT                   /note="For PL-PRO activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   ACT_SITE        1774
FT                   /note="For PL-PRO activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   ACT_SITE        3288
FT                   /note="For 3CL-PRO activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00772"
FT   ACT_SITE        3395
FT                   /note="For 3CL-PRO activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00772"
FT   BINDING         338
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT   BINDING         341
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT   BINDING         357
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT   BINDING         359
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT   BINDING         383
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT   BINDING         386
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT   BINDING         400
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT   BINDING         436
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01333"
FT   BINDING         1672
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   BINDING         1675
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   BINDING         1707
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   BINDING         1709
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   BINDING         2368
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   BINDING         2373
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   BINDING         2378
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   BINDING         2381
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   BINDING         2414
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="5"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   BINDING         2417
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="5"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   BINDING         2421
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="5"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   BINDING         2424
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="5"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01336"
FT   BINDING         4311
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="6"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT   BINDING         4314
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="6"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT   BINDING         4320
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="6"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT   BINDING         4327
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="6"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT   BINDING         4354
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="7"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT   BINDING         4357
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="7"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT   BINDING         4365
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="7"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT   BINDING         4367
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="7"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"
FT   SITE            193..194
FT                   /note="Cleavage"
FT                   /evidence="ECO:0000250"
FT   SITE            853..854
FT                   /note="Cleavage; by PL-PRO"
FT                   /evidence="ECO:0000250"
FT   SITE            2740..2741
FT                   /note="Cleavage; by PL-PRO"
FT                   /evidence="ECO:0000250"
FT   SITE            3247..3248
FT                   /note="Cleavage; by 3CL-PRO"
FT                   /evidence="ECO:0000250"
FT   SITE            3553..3554
FT                   /note="Cleavage; by 3CL-PRO"
FT                   /evidence="ECO:0000250"
FT   SITE            3845..3846
FT                   /note="Cleavage; by 3CL-PRO"
FT                   /evidence="ECO:0000250"
FT   SITE            3928..3929
FT                   /note="Cleavage; by 3CL-PRO"
FT                   /evidence="ECO:0000250"
FT   SITE            4127..4128
FT                   /note="Cleavage; by 3CL-PRO"
FT                   /evidence="ECO:0000250"
FT   SITE            4237..4238
FT                   /note="Cleavage; by 3CL-PRO"
FT                   /evidence="ECO:0000250"
FT   SITE            4377..4378
FT                   /note="Cleavage; by 3CL-PRO"
FT                   /evidence="ECO:0000250"
FT   DISULFID        2230..2258
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01337"
FT   DISULFID        2248..2255
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01337"
FT   HELIX           1110..1113
FT                   /evidence="ECO:0007829|PDB:5DUS"
FT   STRAND          1116..1118
FT                   /evidence="ECO:0007829|PDB:5DUS"
FT   STRAND          1120..1128
FT                   /evidence="ECO:0007829|PDB:5DUS"
FT   HELIX           1130..1134
FT                   /evidence="ECO:0007829|PDB:5DUS"
FT   STRAND          1141..1146
FT                   /evidence="ECO:0007829|PDB:5DUS"
FT   HELIX           1156..1163
FT                   /evidence="ECO:0007829|PDB:5DUS"
FT   TURN            1164..1166
FT                   /evidence="ECO:0007829|PDB:5DUS"
FT   HELIX           1167..1179
FT                   /evidence="ECO:0007829|PDB:5DUS"
FT   STRAND          1187..1191
FT                   /evidence="ECO:0007829|PDB:5DUS"
FT   STRAND          1195..1203
FT                   /evidence="ECO:0007829|PDB:5DUS"
FT   HELIX           1207..1209
FT                   /evidence="ECO:0007829|PDB:5DUS"
FT   HELIX           1213..1215
FT                   /evidence="ECO:0007829|PDB:5DUS"
FT   HELIX           1216..1221
FT                   /evidence="ECO:0007829|PDB:5DUS"
FT   HELIX           1222..1225
FT                   /evidence="ECO:0007829|PDB:5DUS"
FT   STRAND          1226..1231
FT                   /evidence="ECO:0007829|PDB:5DUS"
FT   HELIX           1243..1253
FT                   /evidence="ECO:0007829|PDB:5DUS"
FT   STRAND          1256..1263
FT                   /evidence="ECO:0007829|PDB:5DUS"
FT   HELIX           1265..1272
FT                   /evidence="ECO:0007829|PDB:5DUS"
FT   STRAND          1484..1494
FT                   /evidence="ECO:0007829|PDB:4R3D"
FT   STRAND          1496..1505
FT                   /evidence="ECO:0007829|PDB:4R3D"
FT   HELIX           1507..1510
FT                   /evidence="ECO:0007829|PDB:4R3D"
FT   STRAND          1513..1516
FT                   /evidence="ECO:0007829|PDB:4R3D"
FT   HELIX           1528..1530
FT                   /evidence="ECO:0007829|PDB:4R3D"
FT   STRAND          1534..1537
FT                   /evidence="ECO:0007829|PDB:4R3D"
FT   HELIX           1543..1553
FT                   /evidence="ECO:0007829|PDB:4R3D"
FT   HELIX           1560..1570
FT                   /evidence="ECO:0007829|PDB:4R3D"
FT   TURN            1571..1573
FT                   /evidence="ECO:0007829|PDB:4R3D"
FT   STRAND          1576..1579
FT                   /evidence="ECO:0007829|PDB:4R3D"
FT   STRAND          1582..1585
FT                   /evidence="ECO:0007829|PDB:4R3D"
FT   TURN            1589..1591
FT                   /evidence="ECO:0007829|PDB:4R3D"
FT   HELIX           1592..1603
FT                   /evidence="ECO:0007829|PDB:4R3D"
FT   STRAND          1607..1611
FT                   /evidence="ECO:0007829|PDB:4R3D"
FT   HELIX           1612..1622
FT                   /evidence="ECO:0007829|PDB:4R3D"
FT   HELIX           1627..1636
FT                   /evidence="ECO:0007829|PDB:4R3D"
FT   HELIX           1647..1655
FT                   /evidence="ECO:0007829|PDB:4R3D"
FT   STRAND          1658..1662
FT                   /evidence="ECO:0007829|PDB:4R3D"
FT   STRAND          1665..1672
FT                   /evidence="ECO:0007829|PDB:4R3D"
FT   TURN            1673..1675
FT                   /evidence="ECO:0007829|PDB:4R3D"
FT   STRAND          1676..1683
FT                   /evidence="ECO:0007829|PDB:4R3D"
FT   HELIX           1684..1687
FT                   /evidence="ECO:0007829|PDB:4R3D"
FT   STRAND          1689..1692
FT                   /evidence="ECO:0007829|PDB:4R3D"
FT   HELIX           1696..1699
FT                   /evidence="ECO:0007829|PDB:4R3D"
FT   STRAND          1703..1706
FT                   /evidence="ECO:0007829|PDB:4R3D"
FT   STRAND          1710..1740
FT                   /evidence="ECO:0007829|PDB:4R3D"
FT   STRAND          1745..1751
FT                   /evidence="ECO:0007829|PDB:4R3D"
FT   STRAND          1759..1766
FT                   /evidence="ECO:0007829|PDB:4R3D"
FT   STRAND          1769..1773
FT                   /evidence="ECO:0007829|PDB:4R3D"
FT   STRAND          1780..1799
FT                   /evidence="ECO:0007829|PDB:4R3D"
FT   HELIX           3258..3261
FT                   /evidence="ECO:0007829|PDB:5WKK"
FT   STRAND          3264..3269
FT                   /evidence="ECO:0007829|PDB:5WKK"
FT   STRAND          3273..3279
FT                   /evidence="ECO:0007829|PDB:5WKK"
FT   STRAND          3282..3286
FT                   /evidence="ECO:0007829|PDB:5WKK"
FT   HELIX           3287..3290
FT                   /evidence="ECO:0007829|PDB:5WKK"
FT   HELIX           3293..3295
FT                   /evidence="ECO:0007829|PDB:5WKK"
FT   STRAND          3296..3298
FT                   /evidence="ECO:0007829|PDB:5WKL"
FT   HELIX           3301..3307
FT                   /evidence="ECO:0007829|PDB:5WKK"
FT   HELIX           3310..3312
FT                   /evidence="ECO:0007829|PDB:5WKK"
FT   STRAND          3313..3316
FT                   /evidence="ECO:0007829|PDB:5WKK"
FT   STRAND          3319..3321
FT                   /evidence="ECO:0007829|PDB:7T3Z"
FT   STRAND          3323..3325
FT                   /evidence="ECO:0007829|PDB:7T3Z"
FT   STRAND          3327..3333
FT                   /evidence="ECO:0007829|PDB:5WKK"
FT   STRAND          3336..3343
FT                   /evidence="ECO:0007829|PDB:5WKK"
FT   STRAND          3350..3353
FT                   /evidence="ECO:0007829|PDB:5WKK"
FT   STRAND          3361..3368
FT                   /evidence="ECO:0007829|PDB:5WKK"
FT   STRAND          3371..3379
FT                   /evidence="ECO:0007829|PDB:5WKK"
FT   STRAND          3398..3403
FT                   /evidence="ECO:0007829|PDB:5WKK"
FT   STRAND          3406..3416
FT                   /evidence="ECO:0007829|PDB:5WKK"
FT   STRAND          3422..3425
FT                   /evidence="ECO:0007829|PDB:5WKK"
FT   HELIX           3432..3434
FT                   /evidence="ECO:0007829|PDB:7T3Y"
FT   STRAND          3437..3440
FT                   /evidence="ECO:0007829|PDB:5WKK"
FT   HELIX           3451..3463
FT                   /evidence="ECO:0007829|PDB:5WKK"
FT   HELIX           3477..3485
FT                   /evidence="ECO:0007829|PDB:5WKK"
FT   TURN            3486..3488
FT                   /evidence="ECO:0007829|PDB:5WKK"
FT   HELIX           3496..3505
FT                   /evidence="ECO:0007829|PDB:5WKK"
FT   HELIX           3509..3520
FT                   /evidence="ECO:0007829|PDB:5WKK"
FT   STRAND          3531..3533
FT                   /evidence="ECO:0007829|PDB:5WKK"
FT   HELIX           3540..3546
FT                   /evidence="ECO:0007829|PDB:5WKK"
SQ   SEQUENCE   4391 AA;  486059 MW;  D0A87AE59773BBB8 CRC64;
     MSFVAGVTAQ GARGTYRAAL NSEKHQDHVS LTVPLCGSGN LVEKLSPWFM DGENAYEVVK
     AMLLKKEPLL YVPIRLAGHT RHLPGPRVYL VERLIACENP FMVNQLAYSS SANGSLVGTT
     LQGKPIGMFF PYDIELVTGK QNILLRKYGR GGYHYTPFHY ERDNTSCPEW MDDFEADPKG
     KYAQNLLKKL IGGDVTPVDQ YMCGVDGKPI SAYAFLMAKD GITKLADVEA DVAARADDEG
     FITLKNNLYR LVWHVERKDV PYPKQSIFTI NSVVQKDGVE NTPPHYFTLG CKILTLTPRN
     KWSGVSDLSL KQKLLYTFYG KESLENPTYI YHSAFIECGS CGNDSWLTGN AIQGFACGCG
     ASYTANDVEV QSSGMIKPNA LLCATCPFAK GDSCSSNCKH SVAQLVSYLS ERCNVIADSK
     SFTLIFGGVA YAYFGCEEGT MYFVPRAKSV VSRIGDSIFT GCTGSWNKVT QIANMFLEQT
     QHSLNFVGEF VVNDVVLAIL SGTTTNVDKI RQLLKGVTLD KLRDYLADYD VAVTAGPFMD
     NAINVGGTGL QYAAITAPYV VLTGLGESFK KVATIPYKVC NSVKDTLTYY AHSVLYRVFP
     YDMDSGVSSF SELLFDCVDL SVASTYFLVR LLQDKTGDFM STIITSCQTA VSKLLDTCFE
     ATEATFNFLL DLAGLFRIFL RNAYVYTSQG FVVVNGKVST LVKQVLDLLN KGMQLLHTKV
     SWAGSNISAV IYSGRESLIF PSGTYYCVTT KAKSVQQDLD VILPGEFSKK QLGLLQPTDN
     STTVSVTVSS NMVETVVGQL EQTNMHSPDV IVGDYVIISE KLFVRSKEED GFAFYPACTN
     GHAVPTLFRL KGGAPVKKVA FGGDQVHEVA AVRSVTVEYN IHAVLDTLLA SSSLRTFVVD
     KSLSIEEFAD VVKEQVSDLL VKLLRGMPIP DFDLDDFIDA PCYCFNAEGD ASWSSTMIFS
     LHPVECDEEC SEVEASDLEE GESECISETS TEQVDVSHEI SDDEWAAAVD EAFPLDEAED
     VTESVQEEAQ PVEVPVEDIA QVVIADTLQE TPVVSDTVEV PPQVVKLPSE PQTIQPEVKE
     VAPVYEADTE QTQSVTVKPK RLRKKRNVDP LSNFEHKVIT ECVTIVLGDA IQVAKCYGES
     VLVNAANTHL KHGGGIAGAI NAASKGAVQK ESDEYILAKG PLQVGDSVLL QGHSLAKNIL
     HVVGPDARAK QDVSLLSKCY KAMNAYPLVV TPLVSAGIFG VKPAVSFDYL IREAKTRVLV
     VVNSQDVYKS LTIVDIPQSL TFSYDGLRGA IRKAKDYGFT VFVCTDNSAN TKVLRNKGVD
     YTKKFLTVDG VQYYCYTSKD TLDDILQQAN KSVGIISMPL GYVSHGLDLI QAGSVVRRVN
     VPYVCLLANK EQEAILMSED VKLNPSEDFI KHVRTNGGYN SWHLVEGELL VQDLRLNKLL
     HWSDQTICYK DSVFYVVKNS TAFPFETLSA CRAYLDSRTT QQLTIEVLVT VDGVNFRTVV
     LNNKNTYRSQ LGCVFFNGAD ISDTIPDEKQ NGHSLYLADN LTADETKALK ELYGPVDPTF
     LHRFYSLKAA VHKWKMVVCD KVRSLKLSDN NCYLNAVIMT LDLLKDIKFV IPALQHAFMK
     HKGGDSTDFI ALIMAYGNCT FGAPDDASRL LHTVLAKAEL CCSARMVWRE WCNVCGIKDV
     VLQGLKACCY VGVQTVEDLR ARMTYVCQCG GERHRQIVEH TTPWLLLSGT PNEKLVTTST
     APDFVAFNVF QGIETAVGHY VHARLKGGLI LKFDSGTVSK TSDWKCKVTD VLFPGQKYSS
     DCNVVRYSLD GNFRTEVDPD LSAFYVKDGK YFTSEPPVTY SPATILAGSV YTNSCLVSSD
     GQPGGDAISL SFNNLLGFDS SKPVTKKYTY SFLPKEDGDV LLAEFDTYDP IYKNGAMYKG
     KPILWVNKAS YDTNLNKFNR ASLRQIFDVA PIELENKFTP LSVESTPVEP PTVDVVALQQ
     EMTIVKCKGL NKPFVKDNVS FVADDSGTPV VEYLSKEDLH TLYVDPKYQV IVLKDNVLSS
     MLRLHTVESG DINVVAASGS LTRKVKLLFR ASFYFKEFAT RTFTATTAVG SCIKSVVRHL
     GVTKGILTGC FSFVKMLFML PLAYFSDSKL GTTEVKVSAL KTAGVVTGNV VKQCCTAAVD
     LSMDKLRRVD WKSTLRLLLM LCTTMVLLSS VYHLYVFNQV LSSDVMFEDA QGLKKFYKEV
     RAYLGISSAC DGLASAYRAN SFDVPTFCAN RSAMCNWCLI SQDSITHYPA LKMVQTHLSH
     YVLNIDWLWF AFETGLAYML YTSAFNWLLL AGTLHYFFAQ TSIFVDWRSY NYAVSSAFWL
     FTHIPMAGLV RMYNLLACLW LLRKFYQHVI NGCKDTACLL CYKRNRLTRV EASTVVCGGK
     RTFYITANGG ISFCRRHNWN CVDCDTAGVG NTFICEEVAN DLTTALRRPI NATDRSHYYV
     DSVTVKETVV QFNYRRDGQP FYERFPLCAF TNLDKLKFKE VCKTTTGIPE YNFIIYDSSD
     RGQESLARSA CVYYSQVLCK SILLVDSSLV TSVGDSSEIA TKMFDSFVNS FVSLYNVTRD
     KLEKLISTAR DGVRRGDNFH SVLTTFIDAA RGPAGVESDV ETNEIVDSVQ YAHKHDIQIT
     NESYNNYVPS YVKPDSVSTS DLGSLIDCNA ASVNQIVLRN SNGACIWNAA AYMKLSDALK
     RQIRIACRKC NLAFRLTTSK LRANDNILSV RFTANKIVGG APTWFNALRD FTLKGYVLAT
     IIVFLCAVLM YLCLPTFSMV PVEFYEDRIL DFKVLDNGII RDVNPDDKCF ANKHRSFTQW
     YHEHVGGVYD NSITCPLTVA VIAGVAGARI PDVPTTLAWV NNQIIFFVSR VFANTGSVCY
     TPIDEIPYKS FSDSGCILPS ECTMFRDAEG RMTPYCHDPT VLPGAFAYSQ MRPHVRYDLY
     DGNMFIKFPE VVFESTLRIT RTLSTQYCRF GSCEYAQEGV CITTNGSWAI FNDHHLNRPG
     VYCGSDFIDI VRRLAVSLFQ PITYFQLTTS LVLGIGLCAF LTLLFYYINK VKRAFADYTQ
     CAVIAVVAAV LNSLCICFVA SIPLCIVPYT ALYYYATFYF TNEPAFIMHV SWYIMFGPIV
     PIWMTCVYTV AMCFRHFFWV LAYFSKKHVE VFTDGKLNCS FQDAASNIFV INKDTYAALR
     NSLTNDAYSR FLGLFNKYKY FSGAMETAAY REAAACHLAK ALQTYSETGS DLLYQPPNCS
     ITSGVLQSGL VKMSHPSGDV EACMVQVTCG SMTLNGLWLD NTVWCPRHVM CPADQLSDPN
     YDALLISMTN HSFSVQKHIG APANLRVVGH AMQGTLLKLT VDVANPSTPA YTFTTVKPGA
     AFSVLACYNG RPTGTFTVVM RPNYTIKGSF LCGSCGSVGY TKEGSVINFC YMHQMELANG
     THTGSAFDGT MYGAFMDKQV HQVQLTDKYC SVNVVAWLYA AILNGCAWFV KPNRTSVVSF
     NEWALANQFT EFVGTQSVDM LAVKTGVAIE QLLYAIQQLY TGFQGKQILG STMLEDEFTP
     EDVNMQIMGV VMQSGVRKVT YGTAHWLFAT LVSTYVIILQ ATKFTLWNYL FETIPTQLFP
     LLFVTMAFVM LLVKHKHTFL TLFLLPVAIC LTYANIVYEP TTPISSALIA VANWLAPTNA
     YMRTTHTDIG VYISMSLVLV IVVKRLYNPS LSNFALALCS GVMWLYTYSI GEASSPIAYL
     VFVTTLTSDY TITVFVTVNL AKVCTYAIFA YSPQLTLVFP EVKMILLLYT CLGFMCTCYF
     GVFSLLNLKL RAPMGVYDFK VSTQEFRFMT ANNLTAPRNS WEAMALNFKL IGIGGTPCIK
     VAAMQSKLTD LKCTSVVLLS VLQQLHLEAN SRAWAFCVKC HNDILAATDP SEAFEKFVSL
     FATLMTFSGN VDLDALASDI FDTPSVLQAT LSEFSHLATF AELEAAQKAY QEAMDSGDTS
     PQVLKALQKA VNIAKNAYEK DKAVARKLER MADQAMTSMY KQARAEDKKA KIVSAMQTML
     FGMIKKLDND VLNGIISNAR NGCIPLSVIP LCASNKLRVV IPDFTVWNQV VTYPSLNYAG
     ALWDITVINN VDNEIVKSSD VVDSNENLTW PLVLECTRAS TSAVKLQNNE IKPSGLKTMV
     VSAGQEQTNC NTSSLAYYEP VQGRKMLMAL LSDNAYLKWA RVEGKDGFVS VELQPPCKFL
     IAGPKGPEIR YLYFVKNLNN LHRGQVLGHI AATVRLQAGS NTEFASNSSV LSLVNFTVDP
     QKAYLDFVNA GGAPLTNCVK MLTPKTGTGI AISVKPESTA DQETYGGASV CLYCRAHIEH
     PDVSGVCKYK GKFVQIPAQC VRDPVGFCLS NTPCNVCQYW IGYGCNCDSL RQAALPQSKD
     SNFLNESGVL L
//