PGH1_SHEEP
ID PGH1_SHEEP Reviewed; 600 AA.
AC P05979;
DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT 04-FEB-2015, sequence version 3.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Prostaglandin G/H synthase 1;
DE EC=1.14.99.1 {ECO:0000269|PubMed:7947975};
DE AltName: Full=Cyclooxygenase-1;
DE Short=COX-1;
DE AltName: Full=Prostaglandin H2 synthase 1;
DE Short=PGH synthase 1;
DE Short=PGHS-1;
DE Short=PHS 1;
DE AltName: Full=Prostaglandin-endoperoxide synthase 1;
DE Flags: Precursor;
GN Name=PTGS1; Synonyms=COX1;
OS Ovis aries (Sheep).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Caprinae; Ovis.
OX NCBI_TaxID=9940;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, AND VARIANT GLY-164.
RC TISSUE=Seminal vesicle;
RX PubMed=3125548; DOI=10.1073/pnas.85.5.1412;
RA Dewitt D.L., Smith W.L.;
RT "Primary structure of prostaglandin G/H synthase from sheep vesicular gland
RT determined from the complementary DNA sequence.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:1412-1416(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=3129310; DOI=10.1016/0014-5793(88)80847-0;
RA Yokoyama C., Takai T., Tanabe T.;
RT "Primary structure of sheep prostaglandin endoperoxide synthase deduced
RT from cDNA sequence.";
RL FEBS Lett. 231:347-351(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT GLY-164.
RX PubMed=2831188; DOI=10.1016/s0021-9258(18)68959-8;
RA Merlie J., Fagan D., Mudd J., Needleman P.;
RT "Isolation and characterization of the complementary DNA for sheep seminal
RT vesicle prostaglandin endoperoxide synthase (cyclooxygenase).";
RL J. Biol. Chem. 263:3550-3553(1988).
RN [4]
RP PROTEIN SEQUENCE OF 523-544.
RX PubMed=6414516; DOI=10.1021/bi00289a010;
RA Roth G.J., Machuga E.T., Ozols J.;
RT "Isolation and covalent structure of the aspirin-modified, active-site
RT region of prostaglandin synthetase.";
RL Biochemistry 22:4672-4675(1983).
RN [5]
RP HEME-BINDING SITE.
RX PubMed=2108169; DOI=10.1016/s0021-9258(19)34105-5;
RA Dewitt D.L., El-Harith E.A., Kraemer S.A., Andrews M.J., Yao E.F.,
RA Armstrong R.L., Smith W.L.;
RT "The aspirin and heme-binding sites of ovine and murine prostaglandin
RT endoperoxide synthases.";
RL J. Biol. Chem. 265:5192-5198(1990).
RN [6]
RP ACTIVE SITE TYR-385, AND MUTAGENESIS OF TYR-385.
RX PubMed=2122967; DOI=10.1016/s0021-9258(17)30468-4;
RA Shimokawa T., Kulmacz R.J., Dewitt D.L., Smith W.L.;
RT "Tyrosine 385 of prostaglandin endoperoxide synthase is required for
RT cyclooxygenase catalysis.";
RL J. Biol. Chem. 265:20073-20076(1990).
RN [7]
RP GLYCOSYLATION AT ASN-68; ASN-144 AND ASN-410, AND LACK OF GLYCOSYLATION AT
RP ASN-104.
RX PubMed=8349699; DOI=10.1016/s0021-9258(17)46835-9;
RA Otto J.C., Dewitt D.L., Smith W.L.;
RT "N-glycosylation of prostaglandin endoperoxide synthases-1 and -2 and their
RT orientations in the endoplasmic reticulum.";
RL J. Biol. Chem. 268:18234-18242(1993).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=7947975; DOI=10.1016/0167-4838(94)90148-1;
RA Barnett J., Chow J., Ives D., Chiou M., Mackenzie R., Osen E., Nguyen B.,
RA Tsing S., Bach C., Freire J.;
RT "Purification, characterization and selective inhibition of human
RT prostaglandin G/H synthase 1 and 2 expressed in the baculovirus system.";
RL Biochim. Biophys. Acta 1209:130-139(1994).
RN [9]
RP FUNCTION, AND INHIBITION BY NSAIDS.
RX PubMed=10438452; DOI=10.1074/jbc.274.33.22903;
RA Marnett L.J., Rowlinson S.W., Goodwin D.C., Kalgutkar A.S., Lanzo C.A.;
RT "Arachidonic acid oxygenation by COX-1 and COX-2. Mechanisms of catalysis
RT and inhibition.";
RL J. Biol. Chem. 274:22903-22906(1999).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (3.5 ANGSTROMS).
RX PubMed=8121489; DOI=10.1038/367243a0;
RA Picot D., Loll P.J., Garavito R.M.;
RT "The X-ray crystal structure of the membrane protein prostaglandin H2
RT synthase-1.";
RL Nature 367:243-249(1994).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (3.4 ANGSTROMS).
RX PubMed=7552725; DOI=10.1038/nsb0895-637;
RA Loll P.J., Picot D., Garavito R.M.;
RT "The structural basis of aspirin activity inferred from the crystal
RT structure of inactivated prostaglandin H2 synthase.";
RL Nat. Struct. Biol. 2:637-643(1995).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (3.5 ANGSTROMS).
RX PubMed=8652509; DOI=10.1021/bi952776w;
RA Loll P.J., Picot D., Ekabo O., Garavito R.M.;
RT "Synthesis and use of iodinated antiinflammatory drug analogs as
RT crystallographic probes of the prostaglandin H2 synthase cyclooxygenase
RT active site.";
RL Biochemistry 35:7330-7340(1996).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS).
RX PubMed=10988074; DOI=10.1126/science.289.5486.1933;
RA Malkowski M.G., Ginell S.L., Smith W.L., Garavito R.M.;
RT "The productive conformation of arachidonic acid bound to prostaglandin
RT synthase.";
RL Science 289:1933-1937(2000).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS).
RX PubMed=11121413; DOI=10.1074/jbc.m009378200;
RA Thuresson E.D., Malkowski M.G., Lakkides K.M., Rieke C.J., Mulichak A.M.,
RA Ginell S.L., Garavito R.M., Smith W.L.;
RT "Mutational and X-ray crystallographic analysis of the interaction of
RT dihomo-gamma-linolenic acid with prostaglandin endoperoxide H synthases.";
RL J. Biol. Chem. 276:10358-10365(2001).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.61 ANGSTROMS).
RX PubMed=11318639; DOI=10.1021/bi010045s;
RA Selinsky B.S., Gupta K., Sharkey C.T., Loll P.J.;
RT "Structural analysis of NSAID binding by prostaglandin H2 synthase: time-
RT dependent and time-independent inhibitors elicit identical enzyme
RT conformations.";
RL Biochemistry 40:5172-5180(2001).
CC -!- FUNCTION: Dual cyclooxygenase and peroxidase in the biosynthesis
CC pathway of prostanoids, a class of C20 oxylipins mainly derived from
CC arachidonate, with a particular role in the inflammatory response. The
CC cyclooxygenase activity oxygenates arachidonate (AA, C20:4(n-6)) to the
CC hydroperoxy endoperoxide prostaglandin G2 (PGG2), and the peroxidase
CC activity reduces PGG2 to the hydroxy endoperoxide PGH2, the precursor
CC of all 2-series prostaglandins and thromboxanes. This complex
CC transformation is initiated by abstraction of hydrogen at carbon 13
CC (with S-stereochemistry), followed by insertion of molecular O2 to form
CC the endoperoxide bridge between carbon 9 and 11 that defines
CC prostaglandins. The insertion of a second molecule of O2 (bis-oxygenase
CC activity) yields a hydroperoxy group in PGG2 that is then reduced to
CC PGH2 by two electrons (PubMed:7947975). Involved in the constitutive
CC production of prostanoids in particular in the stomach and platelets.
CC In gastric epithelial cells, it is a key step in the generation of
CC prostaglandins, such as prostaglandin E2 (PGE2), which plays an
CC important role in cytoprotection. In platelets, it is involved in the
CC generation of thromboxane A2 (TXA2), which promotes platelet activation
CC and aggregation, vasoconstriction and proliferation of vascular smooth
CC muscle cells (PubMed:10438452). {ECO:0000269|PubMed:10438452,
CC ECO:0000269|PubMed:7947975}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + AH2 + 2 O2 = A + H2O +
CC prostaglandin H2; Xref=Rhea:RHEA:23728, ChEBI:CHEBI:13193,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:17499,
CC ChEBI:CHEBI:32395, ChEBI:CHEBI:57405; EC=1.14.99.1;
CC Evidence={ECO:0000269|PubMed:7947975};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23729;
CC Evidence={ECO:0000305|PubMed:7947975};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + 2 O2 = prostaglandin G2;
CC Xref=Rhea:RHEA:42596, ChEBI:CHEBI:15379, ChEBI:CHEBI:32395,
CC ChEBI:CHEBI:82629; Evidence={ECO:0000269|PubMed:7947975};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42597;
CC Evidence={ECO:0000305|PubMed:7947975};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=AH2 + prostaglandin G2 = A + H2O + prostaglandin H2;
CC Xref=Rhea:RHEA:42600, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:17499, ChEBI:CHEBI:57405, ChEBI:CHEBI:82629;
CC Evidence={ECO:0000269|PubMed:7947975};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42601;
CC Evidence={ECO:0000305|PubMed:7947975};
CC -!- COFACTOR:
CC Name=heme b; Xref=ChEBI:CHEBI:60344;
CC Note=Binds 1 heme b (iron(II)-protoporphyrin IX) group per subunit.;
CC -!- ACTIVITY REGULATION: The cyclooxygenase activity is inhibited by
CC nonsteroidal anti-inflammatory drugs (NSAIDs) including ibuprofen,
CC flurbiprofen, ketoprofen, naproxen, flurbiprofen, anirolac, fenclofenac
CC and diclofenac. {ECO:0000250|UniProtKB:P23219}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=5.1 uM for arachidonate {ECO:0000269|PubMed:7947975};
CC -!- PATHWAY: Lipid metabolism; prostaglandin biosynthesis.
CC {ECO:0000269|PubMed:7947975}.
CC -!- SUBUNIT: Homodimer.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass
CC membrane protein. Microsome membrane; Multi-pass membrane protein.
CC -!- MISCELLANEOUS: The conversion of arachidonate to prostaglandin H2 is a
CC 2 step reaction: a cyclooxygenase (COX) reaction which converts
CC arachidonate to prostaglandin G2 (PGG2) and a peroxidase reaction in
CC which PGG2 is reduced to prostaglandin H2 (PGH2). The cyclooxygenase
CC reaction occurs in a hydrophobic channel in the core of the enzyme. The
CC peroxidase reaction occurs at a heme-containing active site located
CC near the protein surface. The nonsteroidal anti-inflammatory drugs
CC (NSAIDs) binding site corresponds to the cyclooxygenase active site.
CC -!- MISCELLANEOUS: Conversion of arachidonate to prostaglandin H2 is
CC mediated by 2 different isozymes: the constitutive PTGS1 and the
CC inducible PTGS2. PTGS1 is expressed constitutively and generally
CC produces prostanoids acutely in response to hormonal stimuli to fine-
CC tune physiological processes requiring instantaneous, continuous
CC regulation (e.g. hemostasis). PTGS2 is inducible and typically produces
CC prostanoids that mediate responses to physiological stresses such as
CC infection and inflammation.
CC -!- MISCELLANEOUS: PTGS1 and PTGS2 are the targets of nonsteroidal anti-
CC inflammatory drugs (NSAIDs) including aspirin and ibuprofen. Aspirin is
CC able to produce an irreversible inactivation of the enzyme through a
CC serine acetylation. Inhibition of the PGHSs with NSAIDs acutely reduces
CC inflammation, pain, and fever, and long-term use of these drugs reduces
CC fatal thrombotic events, as well as the development of colon cancer and
CC Alzheimer's disease. PTGS2 is the principal isozyme responsible for
CC production of inflammatory prostaglandins. New generation PTGSs
CC inhibitors strive to be selective for PTGS2, to avoid side effects such
CC as gastrointestinal complications and ulceration.
CC -!- SIMILARITY: Belongs to the prostaglandin G/H synthase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA31576.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; J03599; AAA31576.1; ALT_FRAME; mRNA.
DR EMBL; Y00750; CAA68719.1; -; mRNA.
DR EMBL; M18243; AAA31511.1; -; mRNA.
DR PIR; A28960; A28960.
DR PIR; A29947; A29947.
DR PIR; S00561; S00561.
DR RefSeq; NP_001009476.1; NM_001009476.1.
DR PDB; 1CQE; X-ray; 3.10 A; A/B=21-600.
DR PDB; 1DIY; X-ray; 3.00 A; A=32-584.
DR PDB; 1EBV; X-ray; 3.20 A; A=33-583.
DR PDB; 1EQG; X-ray; 2.61 A; A/B=21-600.
DR PDB; 1EQH; X-ray; 2.70 A; A/B=21-600.
DR PDB; 1FE2; X-ray; 3.00 A; A=25-600.
DR PDB; 1HT5; X-ray; 2.75 A; A/B=33-583.
DR PDB; 1HT8; X-ray; 2.69 A; A/B=33-583.
DR PDB; 1IGX; X-ray; 3.10 A; A=25-600.
DR PDB; 1IGZ; X-ray; 2.90 A; A=25-600.
DR PDB; 1PGE; X-ray; 3.50 A; A/B=25-600.
DR PDB; 1PGF; X-ray; 4.50 A; A/B=25-600.
DR PDB; 1PGG; X-ray; 4.50 A; A/B=25-600.
DR PDB; 1PRH; X-ray; 3.50 A; A/B=33-586.
DR PDB; 1PTH; X-ray; 3.40 A; A/B=25-600.
DR PDB; 1Q4G; X-ray; 2.00 A; A/B=32-584.
DR PDB; 1U67; X-ray; 3.10 A; A=1-600.
DR PDB; 2AYL; X-ray; 2.00 A; A/B=32-584.
DR PDB; 2OYE; X-ray; 2.85 A; P=1-600.
DR PDB; 2OYU; X-ray; 2.70 A; P=1-600.
DR PDB; 3KK6; X-ray; 2.75 A; A/B=32-584.
DR PDB; 3N8V; X-ray; 3.05 A; A/B=32-584.
DR PDB; 3N8W; X-ray; 2.75 A; A/B=32-584.
DR PDB; 3N8X; X-ray; 2.75 A; A/B=32-584.
DR PDB; 3N8Y; X-ray; 2.60 A; A/B=32-584.
DR PDB; 3N8Z; X-ray; 2.90 A; A/B=32-584.
DR PDB; 4O1Z; X-ray; 2.40 A; A/B=32-600.
DR PDB; 5U6X; X-ray; 2.93 A; A/B=1-600.
DR PDB; 5WBE; X-ray; 2.75 A; A/B=1-600.
DR PDB; 7JXT; X-ray; 3.35 A; A/B=32-584.
DR PDBsum; 1CQE; -.
DR PDBsum; 1DIY; -.
DR PDBsum; 1EBV; -.
DR PDBsum; 1EQG; -.
DR PDBsum; 1EQH; -.
DR PDBsum; 1FE2; -.
DR PDBsum; 1HT5; -.
DR PDBsum; 1HT8; -.
DR PDBsum; 1IGX; -.
DR PDBsum; 1IGZ; -.
DR PDBsum; 1PGE; -.
DR PDBsum; 1PGF; -.
DR PDBsum; 1PGG; -.
DR PDBsum; 1PRH; -.
DR PDBsum; 1PTH; -.
DR PDBsum; 1Q4G; -.
DR PDBsum; 1U67; -.
DR PDBsum; 2AYL; -.
DR PDBsum; 2OYE; -.
DR PDBsum; 2OYU; -.
DR PDBsum; 3KK6; -.
DR PDBsum; 3N8V; -.
DR PDBsum; 3N8W; -.
DR PDBsum; 3N8X; -.
DR PDBsum; 3N8Y; -.
DR PDBsum; 3N8Z; -.
DR PDBsum; 4O1Z; -.
DR PDBsum; 5U6X; -.
DR PDBsum; 5WBE; -.
DR PDBsum; 7JXT; -.
DR AlphaFoldDB; P05979; -.
DR SMR; P05979; -.
DR STRING; 9940.ENSOARP00000015152; -.
DR BindingDB; P05979; -.
DR ChEMBL; CHEMBL2949; -.
DR DrugCentral; P05979; -.
DR MoonProt; P05979; -.
DR PeroxiBase; 4121; OarPGHS01.
DR iPTMnet; P05979; -.
DR GeneID; 443551; -.
DR KEGG; oas:443551; -.
DR CTD; 5742; -.
DR eggNOG; KOG2408; Eukaryota.
DR OrthoDB; 324380at2759; -.
DR BRENDA; 1.14.99.1; 2668.
DR SABIO-RK; P05979; -.
DR UniPathway; UPA00662; -.
DR EvolutionaryTrace; P05979; -.
DR PRO; PR:P05979; -.
DR Proteomes; UP000002356; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISS:UniProtKB.
DR GO; GO:0051213; F:dioxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0020037; F:heme binding; IDA:CAFA.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004601; F:peroxidase activity; IEA:UniProtKB-KW.
DR GO; GO:0004666; F:prostaglandin-endoperoxide synthase activity; IMP:CAFA.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:CAFA.
DR GO; GO:0019371; P:cyclooxygenase pathway; IMP:CAFA.
DR GO; GO:0006954; P:inflammatory response; IEA:InterPro.
DR GO; GO:0001516; P:prostaglandin biosynthetic process; ISS:UniProtKB.
DR GO; GO:0008217; P:regulation of blood pressure; ISS:UniProtKB.
DR GO; GO:0006979; P:response to oxidative stress; IEA:InterPro.
DR Gene3D; 1.10.640.10; -; 1.
DR InterPro; IPR029580; COX-1.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR019791; Haem_peroxidase_animal.
DR InterPro; IPR010255; Haem_peroxidase_sf.
DR InterPro; IPR037120; Haem_peroxidase_sf_animal.
DR PANTHER; PTHR11903:SF6; PTHR11903:SF6; 1.
DR Pfam; PF03098; An_peroxidase; 1.
DR Pfam; PF00008; EGF; 1.
DR PRINTS; PR00457; ANPEROXIDASE.
DR SUPFAM; SSF48113; SSF48113; 1.
DR PROSITE; PS50026; EGF_3; 1.
DR PROSITE; PS50292; PEROXIDASE_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Dioxygenase; Direct protein sequencing; Disulfide bond;
KW EGF-like domain; Endoplasmic reticulum; Fatty acid biosynthesis;
KW Fatty acid metabolism; Glycoprotein; Heme; Iron; Lipid biosynthesis;
KW Lipid metabolism; Membrane; Metal-binding; Microsome; Oxidoreductase;
KW Peroxidase; Prostaglandin biosynthesis; Prostaglandin metabolism;
KW Reference proteome; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..24
FT CHAIN 25..600
FT /note="Prostaglandin G/H synthase 1"
FT /id="PRO_0000023871"
FT TRANSMEM 74..82
FT /note="Helical"
FT TRANSMEM 86..92
FT /note="Helical"
FT TRANSMEM 97..105
FT /note="Helical"
FT TRANSMEM 108..122
FT /note="Helical"
FT DOMAIN 32..70
FT /note="EGF-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT ACT_SITE 207
FT /note="Proton acceptor"
FT ACT_SITE 385
FT /note="For cyclooxygenase activity"
FT /evidence="ECO:0000269|PubMed:2122967"
FT BINDING 388
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT SITE 104
FT /note="Not glycosylated"
FT /evidence="ECO:0000269|PubMed:8349699"
FT SITE 530
FT /note="Aspirin-acetylated serine"
FT CARBOHYD 68
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:8349699"
FT CARBOHYD 144
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:8349699"
FT CARBOHYD 410
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:8349699"
FT DISULFID 36..47
FT DISULFID 37..159
FT DISULFID 41..57
FT DISULFID 59..69
FT DISULFID 569..575
FT VARIANT 97
FT /note="R -> H"
FT VARIANT 164
FT /note="D -> G"
FT /evidence="ECO:0000269|PubMed:2831188,
FT ECO:0000269|PubMed:3125548"
FT VARIANT 456
FT /note="R -> Q"
FT VARIANT 520
FT /note="E -> K"
FT VARIANT 520
FT /note="E -> Q"
FT VARIANT 525
FT /note="M -> I"
FT MUTAGEN 385
FT /note="Y->F: Abolishes cyclooxygenase activity."
FT /evidence="ECO:0000269|PubMed:2122967"
FT CONFLICT 1..5
FT /note="MSRQS -> MVQG (in Ref. 3; AAA31511)"
FT /evidence="ECO:0000305"
FT CONFLICT 193
FT /note="S -> G (in Ref. 1; AAA31576 and 3; AAA31511)"
FT /evidence="ECO:0000305"
FT CONFLICT 540
FT /note="C -> E (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT HELIX 35..38
FT /evidence="ECO:0007829|PDB:1Q4G"
FT STRAND 46..50
FT /evidence="ECO:0007829|PDB:1Q4G"
FT TURN 51..53
FT /evidence="ECO:0007829|PDB:1Q4G"
FT STRAND 54..58
FT /evidence="ECO:0007829|PDB:1Q4G"
FT STRAND 62..65
FT /evidence="ECO:0007829|PDB:1Q4G"
FT TURN 66..69
FT /evidence="ECO:0007829|PDB:1Q4G"
FT HELIX 74..82
FT /evidence="ECO:0007829|PDB:1Q4G"
FT HELIX 86..93
FT /evidence="ECO:0007829|PDB:1Q4G"
FT HELIX 97..103
FT /evidence="ECO:0007829|PDB:1Q4G"
FT HELIX 108..121
FT /evidence="ECO:0007829|PDB:1Q4G"
FT STRAND 130..133
FT /evidence="ECO:0007829|PDB:1Q4G"
FT STRAND 134..136
FT /evidence="ECO:0007829|PDB:1EQG"
FT HELIX 139..143
FT /evidence="ECO:0007829|PDB:1Q4G"
FT STRAND 149..152
FT /evidence="ECO:0007829|PDB:1Q4G"
FT STRAND 159..161
FT /evidence="ECO:0007829|PDB:1EQG"
FT STRAND 164..167
FT /evidence="ECO:0007829|PDB:1Q4G"
FT HELIX 174..181
FT /evidence="ECO:0007829|PDB:1Q4G"
FT HELIX 196..206
FT /evidence="ECO:0007829|PDB:1Q4G"
FT TURN 207..209
FT /evidence="ECO:0007829|PDB:1Q4G"
FT TURN 214..216
FT /evidence="ECO:0007829|PDB:1Q4G"
FT STRAND 220..222
FT /evidence="ECO:0007829|PDB:1Q4G"
FT STRAND 227..229
FT /evidence="ECO:0007829|PDB:1Q4G"
FT HELIX 231..234
FT /evidence="ECO:0007829|PDB:1Q4G"
FT HELIX 238..244
FT /evidence="ECO:0007829|PDB:1Q4G"
FT STRAND 255..257
FT /evidence="ECO:0007829|PDB:1Q4G"
FT STRAND 260..262
FT /evidence="ECO:0007829|PDB:1Q4G"
FT TURN 266..268
FT /evidence="ECO:0007829|PDB:1Q4G"
FT HELIX 281..283
FT /evidence="ECO:0007829|PDB:1Q4G"
FT STRAND 288..291
FT /evidence="ECO:0007829|PDB:3KK6"
FT HELIX 292..294
FT /evidence="ECO:0007829|PDB:1Q4G"
FT HELIX 296..319
FT /evidence="ECO:0007829|PDB:1Q4G"
FT HELIX 325..346
FT /evidence="ECO:0007829|PDB:1Q4G"
FT HELIX 348..353
FT /evidence="ECO:0007829|PDB:1Q4G"
FT HELIX 363..366
FT /evidence="ECO:0007829|PDB:1Q4G"
FT STRAND 367..369
FT /evidence="ECO:0007829|PDB:5WBE"
FT HELIX 379..384
FT /evidence="ECO:0007829|PDB:1Q4G"
FT HELIX 388..390
FT /evidence="ECO:0007829|PDB:1Q4G"
FT STRAND 393..397
FT /evidence="ECO:0007829|PDB:1Q4G"
FT STRAND 400..402
FT /evidence="ECO:0007829|PDB:1Q4G"
FT HELIX 404..407
FT /evidence="ECO:0007829|PDB:1Q4G"
FT HELIX 413..417
FT /evidence="ECO:0007829|PDB:1Q4G"
FT HELIX 419..428
FT /evidence="ECO:0007829|PDB:1Q4G"
FT STRAND 434..438
FT /evidence="ECO:0007829|PDB:1Q4G"
FT TURN 442..444
FT /evidence="ECO:0007829|PDB:1Q4G"
FT HELIX 445..457
FT /evidence="ECO:0007829|PDB:1Q4G"
FT HELIX 463..469
FT /evidence="ECO:0007829|PDB:1Q4G"
FT HELIX 478..482
FT /evidence="ECO:0007829|PDB:1Q4G"
FT STRAND 483..485
FT /evidence="ECO:0007829|PDB:1Q4G"
FT HELIX 486..495
FT /evidence="ECO:0007829|PDB:1Q4G"
FT HELIX 498..500
FT /evidence="ECO:0007829|PDB:1Q4G"
FT HELIX 503..509
FT /evidence="ECO:0007829|PDB:1Q4G"
FT STRAND 517..519
FT /evidence="ECO:0007829|PDB:2OYU"
FT HELIX 520..535
FT /evidence="ECO:0007829|PDB:1Q4G"
FT HELIX 538..540
FT /evidence="ECO:0007829|PDB:1Q4G"
FT TURN 542..544
FT /evidence="ECO:0007829|PDB:1Q4G"
FT HELIX 547..550
FT /evidence="ECO:0007829|PDB:1Q4G"
FT HELIX 553..560
FT /evidence="ECO:0007829|PDB:1Q4G"
FT HELIX 564..569
FT /evidence="ECO:0007829|PDB:1Q4G"
FT STRAND 572..574
FT /evidence="ECO:0007829|PDB:1Q4G"
SQ SEQUENCE 600 AA; 68861 MW; 809887C7BB5A715C CRC64;
MSRQSISLRF PLLLLLLSPS PVFSADPGAP APVNPCCYYP CQHQGICVRF GLDRYQCDCT
RTGYSGPNCT IPEIWTWLRT TLRPSPSFIH FLLTHGRWLW DFVNATFIRD TLMRLVLTVR
SNLIPSPPTY NIAHDYISWE SFSNVSYYTR ILPSVPRDCP TPMDTKGKKQ LPDAEFLSRR
FLLRRKFIPD PQSTNLMFAF FAQHFTHQFF KTSGKMGPGF TKALGHGVDL GHIYGDNLER
QYQLRLFKDG KLKYQMLNGE VYPPSVEEAP VLMHYPRGIP PQSQMAVGQE VFGLLPGLML
YATIWLREHN RVCDLLKAEH PTWGDEQLFQ TARLILIGET IKIVIEEYVQ QLSGYFLQLK
FDPELLFGAQ FQYRNRIAME FNQLYHWHPL MPDSFRVGPQ DYSYEQFLFN TSMLVDYGVE
ALVDAFSRQP AGRIGGGRNI DHHILHVAVD VIKESRVLRL QPFNEYRKRF GMKPYTSFQE
LTGEKEMAAE LEELYGDIDA LEFYPGLLLE KCHPNSIFGE SMIEMGAPFS LKGLLGNPIC
SPEYWKASTF GGEVGFNLVK TATLKKLVCL NTKTCPYVSF HVPDPRQEDR PGVERPPTEL
