PLCG1_BOVIN
ID PLCG1_BOVIN Reviewed; 1291 AA.
AC P08487;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1988, sequence version 1.
DT 03-AUG-2022, entry version 207.
DE RecName: Full=1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1;
DE EC=3.1.4.11 {ECO:0000250|UniProtKB:P10686};
DE AltName: Full=PLC-148;
DE AltName: Full=Phosphoinositide phospholipase C-gamma-1;
DE AltName: Full=Phospholipase C-II;
DE Short=PLC-II;
DE AltName: Full=Phospholipase C-gamma-1;
DE Short=PLC-gamma-1;
GN Name=PLCG1;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=2831461; DOI=10.1038/332269a0;
RA Stahl M.L., Ferenz C.R., Kelleher K.L., Kriz R.W., Knopf J.L.;
RT "Sequence similarity of phospholipase C with the non-catalytic region of
RT src.";
RL Nature 332:269-272(1988).
RN [2]
RP PHOSPHORYLATION AT TYR-771; TYR-783 AND TYR-1254.
RX PubMed=1689310; DOI=10.1016/s0021-9258(19)39684-x;
RA Kim J.W., Sim S.S., Kim U.H., Nishibe S., Whal M.I., Carpenter G.,
RA Rhee S.G.;
RT "Tyrosine residues in bovine phospholipase C-gamma phosphorylated by the
RT epidermal growth factor receptor in vitro.";
RL J. Biol. Chem. 265:3940-3943(1990).
RN [3]
RP PHOSPHORYLATION AT TYR-771; TYR-783 AND TYR-1254.
RX PubMed=1689311; DOI=10.1016/s0021-9258(19)39685-1;
RA Whal M.I., Nishibe S., Kim J.W., Kim H.K., Rhee S.G., Carpenter G.;
RT "Identification of two epidermal growth factor-sensitive tyrosine
RT phosphorylation sites of phospholipase C-gamma in intact HSC-1 cells.";
RL J. Biol. Chem. 265:3944-3948(1990).
RN [4]
RP INTERACTION WITH PDGFRA.
RX PubMed=2173144; DOI=10.1126/science.2173144;
RA Anderson D., Koch C.A., Grey L., Ellis C., Moran M.F., Pawson T.;
RT "Binding of SH2 domains of phospholipase C gamma 1, GAP, and Src to
RT activated growth factor receptors.";
RL Science 250:979-982(1990).
RN [5]
RP PHOSPHORYLATION AT TYR-783 AND TYR-1254.
RX PubMed=1708307; DOI=10.1016/0092-8674(91)90461-7;
RA Kim H.K., Kim J.W., Zilberstein A., Margolis B., Kim J.G., Schlessinger J.,
RA Rhee S.G.;
RT "PDGF stimulation of inositol phospholipid hydrolysis requires PLC-gamma 1
RT phosphorylation on tyrosine residues 783 and 1254.";
RL Cell 65:435-441(1991).
RN [6]
RP INTERACTION WITH RET.
RX PubMed=8631863; DOI=10.1074/jbc.271.18.10607;
RA Pandey A., Liu X., Dixon J.E., Di Fiore P.P., Dixit V.M.;
RT "Direct association between the Ret receptor tyrosine kinase and the Src
RT homology 2-containing adapter protein Grb7.";
RL J. Biol. Chem. 271:10607-10610(1996).
RN [7]
RP STRUCTURE BY NMR OF 663-759.
RX PubMed=8181064; DOI=10.1016/0092-8674(94)90160-0;
RA Pascal S.M., Singer A.U., Gish G., Yamazaki T., Shoelson S.E., Pawson T.,
RA Kay L.E., Forman-Kay J.D.;
RT "Nuclear magnetic resonance structure of an SH2 domain of phospholipase C-
RT gamma 1 complexed with a high affinity binding peptide.";
RL Cell 77:461-472(1994).
CC -!- FUNCTION: Mediates the production of the second messenger molecules
CC diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). Plays an
CC important role in the regulation of intracellular signaling cascades.
CC Becomes activated in response to ligand-mediated activation of
CC receptor-type tyrosine kinases, such as PDGFRA, PDGFRB, EGFR, FGFR1,
CC FGFR2, FGFR3 and FGFR4 (By similarity). Plays a role in actin
CC reorganization and cell migration (By similarity).
CC {ECO:0000250|UniProtKB:P10686, ECO:0000250|UniProtKB:P19174,
CC ECO:0000250|UniProtKB:Q62077}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-
CC bisphosphate) + H2O = 1D-myo-inositol 1,4,5-trisphosphate + a 1,2-
CC diacyl-sn-glycerol + H(+); Xref=Rhea:RHEA:33179, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17815, ChEBI:CHEBI:58456,
CC ChEBI:CHEBI:203600; EC=3.1.4.11;
CC Evidence={ECO:0000250|UniProtKB:P10686};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33180;
CC Evidence={ECO:0000250|UniProtKB:P10686};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) + H2O =
CC 1D-myo-inositol 1-phosphate + a 1,2-diacyl-sn-glycerol + H(+);
CC Xref=Rhea:RHEA:43484, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17815, ChEBI:CHEBI:57880, ChEBI:CHEBI:58433;
CC Evidence={ECO:0000250|UniProtKB:P10686};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43485;
CC Evidence={ECO:0000250|UniProtKB:P10686};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000250|UniProtKB:P10686};
CC -!- ACTIVITY REGULATION: Activated by phosphorylation on tyrosine residues.
CC {ECO:0000250|UniProtKB:P19174}.
CC -!- SUBUNIT: Interacts with AGAP2 via its SH3 domain. Interacts (via SH2
CC domain) with RET. Interacts with FLT1 (tyrosine-phosphorylated) (By
CC similarity). Interacts (via SH2 domain) with FGFR1, FGFR2, FGFR3 and
CC FGFR4 (phosphorylated). Interacts with LAT (phosphorylated) upon TCR
CC activation. Interacts (via SH3 domain) with the Pro-rich domain of
CC TNK1. Associates with BLNK, VAV1, GRB2 and NCK1 in a B-cell antigen
CC receptor-dependent fashion. Interacts with CBLB in activated T-cells;
CC which inhibits phosphorylation. Interacts with SHB. Interacts (via SH3
CC domain) with the Arg/Gly-rich-flanked Pro-rich domains of
CC KHDRBS1/SAM68. This interaction is selectively regulated by arginine
CC methylation of KHDRBS1/SAM68. Interacts with INPP5D/SHIP1, THEMIS and
CC CLNK (By similarity). Interacts with AXL, FLT4 and KIT. Interacts with
CC RALGPS1. Interacts (via the SH2 domains) with VIL1 (phosphorylated at
CC C-terminus tyrosine phosphorylation sites). Interacts (via SH2 domain)
CC with PDGFRA and PDGFRB (tyrosine phosphorylated). Interacts with
CC PIP5K1C (By similarity). Interacts with NTRK1 and NTRK2 (phosphorylated
CC upon ligand-binding). Interacts with SYK; activates PLCG1. Interacts
CC with GRB2, LAT and THEMIS upon TCR activation in thymocytes (By
CC similarity). Interacts with TESPA1; the association is increased with
CC prolonged stimulation of the TCR and may facilitate the assembly of the
CC LAT signalosome (By similarity). {ECO:0000250|UniProtKB:P19174,
CC ECO:0000250|UniProtKB:Q62077}.
CC -!- INTERACTION:
CC P08487; P22681: CBL; Xeno; NbExp=3; IntAct=EBI-8013886, EBI-518228;
CC P08487; Q03526: Itk; Xeno; NbExp=4; IntAct=EBI-8013886, EBI-647969;
CC P08487; O43561-2: LAT; Xeno; NbExp=4; IntAct=EBI-8013886, EBI-8070286;
CC P08487; Q13094: LCP2; Xeno; NbExp=5; IntAct=EBI-8013886, EBI-346946;
CC P08487; P09619: PDGFRB; Xeno; NbExp=3; IntAct=EBI-8013886, EBI-641237;
CC P08487; P48025: Syk; Xeno; NbExp=4; IntAct=EBI-8013886, EBI-300116;
CC P08487; P15498: VAV1; Xeno; NbExp=4; IntAct=EBI-8013886, EBI-625518;
CC -!- SUBCELLULAR LOCATION: Cell projection, lamellipodium
CC {ECO:0000250|UniProtKB:P19174}. Cell projection, ruffle
CC {ECO:0000250|UniProtKB:P19174}. Note=Rapidly redistributed to ruffles
CC and lamellipodia structures in response to epidermal growth factor
CC (EGF) treatment. {ECO:0000250|UniProtKB:P19174}.
CC -!- DOMAIN: The SH3 domain mediates interaction with CLNK (By similarity).
CC The SH3 domain also mediates interaction with RALGPS1 (By similarity).
CC {ECO:0000250|UniProtKB:P19174, ECO:0000250|UniProtKB:Q62077}.
CC -!- PTM: Ubiquitinated by CBLB in activated T-cells.
CC {ECO:0000250|UniProtKB:Q62077}.
CC -!- PTM: Tyrosine phosphorylated in response to signaling via activated
CC FLT3, KIT and PDGFRA (By similarity). Tyrosine phosphorylated by
CC activated FGFR1, FGFR2, FGFR3 and FGFR4. Tyrosine phosphorylated by
CC activated FLT1 and KDR. Tyrosine phosphorylated by activated PDGFRB.
CC The receptor-mediated activation of PLCG1 involves its phosphorylation
CC by tyrosine kinases, in response to ligation of a variety of growth
CC factor receptors and immune system receptors. For instance, SYK
CC phosphorylates and activates PLCG1 in response to ligation of the B-
CC cell receptor. May be dephosphorylated by PTPRJ. Phosphorylated by ITK
CC and TXK on Tyr-783 upon TCR activation in T-cells (By similarity).
CC {ECO:0000250|UniProtKB:P19174, ECO:0000250|UniProtKB:Q62077}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; Y00301; CAA68406.1; -; mRNA.
DR PIR; S00666; S00666.
DR RefSeq; NP_776850.1; NM_174425.3.
DR PDB; 2FCI; NMR; -; A=663-759.
DR PDB; 2PLD; NMR; -; A=663-759.
DR PDB; 2PLE; NMR; -; A=663-759.
DR PDB; 5TNW; X-ray; 1.40 A; A/B=663-759.
DR PDB; 5TO4; X-ray; 1.70 A; A=663-759.
DR PDB; 5TQ1; X-ray; 1.49 A; A=663-759.
DR PDB; 5TQS; X-ray; 1.88 A; A/B/C/D=663-759.
DR PDBsum; 2FCI; -.
DR PDBsum; 2PLD; -.
DR PDBsum; 2PLE; -.
DR PDBsum; 5TNW; -.
DR PDBsum; 5TO4; -.
DR PDBsum; 5TQ1; -.
DR PDBsum; 5TQS; -.
DR AlphaFoldDB; P08487; -.
DR SMR; P08487; -.
DR BioGRID; 159276; 1.
DR DIP; DIP-42760N; -.
DR IntAct; P08487; 9.
DR MINT; P08487; -.
DR STRING; 9913.ENSBTAP00000023383; -.
DR BindingDB; P08487; -.
DR ChEMBL; CHEMBL5566; -.
DR iPTMnet; P08487; -.
DR PaxDb; P08487; -.
DR PRIDE; P08487; -.
DR GeneID; 281987; -.
DR KEGG; bta:281987; -.
DR CTD; 5335; -.
DR eggNOG; KOG1264; Eukaryota.
DR InParanoid; P08487; -.
DR OrthoDB; 368239at2759; -.
DR EvolutionaryTrace; P08487; -.
DR PRO; PR:P08487; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0008180; C:COP9 signalosome; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:ARUK-UCL.
DR GO; GO:0030027; C:lamellipodium; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0001726; C:ruffle; ISS:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0050429; F:calcium-dependent phospholipase C activity; ISS:UniProtKB.
DR GO; GO:0004435; F:phosphatidylinositol phospholipase C activity; ISS:UniProtKB.
DR GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; ISS:UniProtKB.
DR GO; GO:0035924; P:cellular response to vascular endothelial growth factor stimulus; IDA:BHF-UCL.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0001701; P:in utero embryonic development; ISS:AgBase.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0046488; P:phosphatidylinositol metabolic process; ISS:UniProtKB.
DR GO; GO:0009395; P:phospholipid catabolic process; IEA:InterPro.
DR GO; GO:0010634; P:positive regulation of epithelial cell migration; ISS:UniProtKB.
DR CDD; cd09932; SH2_C-SH2_PLC_gamma_like; 1.
DR CDD; cd10341; SH2_N-SH2_PLC_gamma_like; 1.
DR CDD; cd11970; SH3_PLCgamma1; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 2.60.40.150; -; 1.
DR Gene3D; 3.20.20.190; -; 2.
DR Gene3D; 3.30.505.10; -; 2.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR001192; PI-PLC_fam.
DR InterPro; IPR016279; PLC-gamma.
DR InterPro; IPR028380; PLC-gamma1.
DR InterPro; IPR035023; PLC-gamma_C-SH2.
DR InterPro; IPR035024; PLC-gamma_N-SH2.
DR InterPro; IPR017946; PLC-like_Pdiesterase_TIM-brl.
DR InterPro; IPR035724; PLCgamma1_SH3.
DR InterPro; IPR000909; PLipase_C_PInositol-sp_X_dom.
DR InterPro; IPR001711; PLipase_C_Pinositol-sp_Y.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR PANTHER; PTHR10336; PTHR10336; 1.
DR PANTHER; PTHR10336:SF173; PTHR10336:SF173; 1.
DR Pfam; PF00168; C2; 1.
DR Pfam; PF00388; PI-PLC-X; 1.
DR Pfam; PF00387; PI-PLC-Y; 1.
DR Pfam; PF00017; SH2; 2.
DR Pfam; PF00018; SH3_1; 1.
DR PIRSF; PIRSF000952; PLC-gamma; 1.
DR PRINTS; PR00390; PHPHLIPASEC.
DR PRINTS; PR00401; SH2DOMAIN.
DR PRINTS; PR00452; SH3DOMAIN.
DR SMART; SM00239; C2; 1.
DR SMART; SM00233; PH; 3.
DR SMART; SM00148; PLCXc; 1.
DR SMART; SM00149; PLCYc; 1.
DR SMART; SM00252; SH2; 2.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF47473; SSF47473; 1.
DR SUPFAM; SSF49562; SSF49562; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR SUPFAM; SSF51695; SSF51695; 1.
DR SUPFAM; SSF55550; SSF55550; 2.
DR PROSITE; PS50004; C2; 1.
DR PROSITE; PS00018; EF_HAND_1; 1.
DR PROSITE; PS50222; EF_HAND_2; 1.
DR PROSITE; PS50003; PH_DOMAIN; 2.
DR PROSITE; PS50007; PIPLC_X_DOMAIN; 1.
DR PROSITE; PS50008; PIPLC_Y_DOMAIN; 1.
DR PROSITE; PS50001; SH2; 2.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Calcium; Cell projection;
KW Direct protein sequencing; Hydrolase; Lipid degradation; Lipid metabolism;
KW Metal-binding; Phosphoprotein; Reference proteome; Repeat; SH2 domain;
KW SH3 domain; Transducer; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P19174"
FT CHAIN 2..1291
FT /note="1-phosphatidylinositol 4,5-bisphosphate
FT phosphodiesterase gamma-1"
FT /id="PRO_0000088497"
FT DOMAIN 27..142
FT /note="PH 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 152..187
FT /note="EF-hand"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 320..464
FT /note="PI-PLC X-box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00270"
FT DOMAIN 489..523
FT /note="PH 2; first part"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 550..657
FT /note="SH2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 668..756
FT /note="SH2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 791..851
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 895..931
FT /note="PH 2; second part"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 953..1070
FT /note="PI-PLC Y-box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00271"
FT DOMAIN 1071..1194
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 522..544
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1271..1291
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 335
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00270"
FT ACT_SITE 380
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00270"
FT BINDING 165
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 167
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 169
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 171
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 176
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:P19174"
FT MOD_RES 506
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q62077"
FT MOD_RES 771
FT /note="Phosphotyrosine; by SYK"
FT /evidence="ECO:0000269|PubMed:1689310,
FT ECO:0000269|PubMed:1689311"
FT MOD_RES 775
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P19174"
FT MOD_RES 783
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:1689310,
FT ECO:0000269|PubMed:1689311, ECO:0000269|PubMed:1708307"
FT MOD_RES 783
FT /note="Phosphotyrosine; by ITK, SYK and TXK"
FT /evidence="ECO:0000250"
FT MOD_RES 977
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q62077"
FT MOD_RES 1222
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P19174"
FT MOD_RES 1228
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P19174"
FT MOD_RES 1249
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P19174"
FT MOD_RES 1254
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:1689310,
FT ECO:0000269|PubMed:1689311, ECO:0000269|PubMed:1708307"
FT MOD_RES 1264
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P19174"
FT HELIX 663..665
FT /evidence="ECO:0007829|PDB:5TNW"
FT STRAND 669..672
FT /evidence="ECO:0007829|PDB:5TNW"
FT HELIX 675..681
FT /evidence="ECO:0007829|PDB:5TNW"
FT STRAND 685..688
FT /evidence="ECO:0007829|PDB:2FCI"
FT STRAND 690..695
FT /evidence="ECO:0007829|PDB:5TNW"
FT STRAND 697..700
FT /evidence="ECO:0007829|PDB:2PLE"
FT STRAND 701..708
FT /evidence="ECO:0007829|PDB:5TNW"
FT STRAND 711..720
FT /evidence="ECO:0007829|PDB:5TNW"
FT STRAND 723..726
FT /evidence="ECO:0007829|PDB:5TNW"
FT STRAND 729..733
FT /evidence="ECO:0007829|PDB:5TNW"
FT HELIX 734..743
FT /evidence="ECO:0007829|PDB:5TNW"
FT STRAND 746..749
FT /evidence="ECO:0007829|PDB:2PLD"
SQ SEQUENCE 1291 AA; 148313 MW; 9F31C7DAA3F8EA77 CRC64;
MAGAASPCAN GCGPSAPSDA EVVHLCRSLE VGTVMTLFYS KKSQRPERKT FQVKLETRQI
TWSRGADKIE GAIDIREIKE IRPGKTSRDF DRYQEDPAFR PDQSHCFVIL YGMEFRLKTL
SLQATSEDEV NMWIRGLTWL MEDTLQAATP LQIERWLRKQ FYSVDRNRED RISAKDLKNM
LSQVNYRVPN MRFLRERLTD LEQRTSDITY GQFAQLYRSL MYSAQKTMDL PFLEASALRA
GERPELCRVS LPEFQQFLLE YQGELWAVDR LQVQEFMLSF LRDPLREIEE PYFFLDEFVT
FLFSKENSIW NSQLDEVCPD TMNNPLSHYW ISSSHNTYLT GDQFSSESSL EAYARCLRMG
CRCIELDCWD GPDGMPVIYH GHTLTTKIKF SDVLHTIKEH AFVASEYPVI LSIEDHCSIA
QQRNMAQYFK KVLGDTLLTK PVDIAADGLP SPNQLKRKIL IKHKKLAEGS AYEEVPTSVM
YSENDISNSI KNGILYLEDP VNHEWYPHYF VLTSSKIYYS EETSSDQGNE DEEEPKEASG
STELHSNEKW FHGKLGAGRD GRHIAERLLT EYCIETGAPD GSFLVRESET FVGDYTLSFW
RNGKVQHCRI HSRQDAGTPK FFLTDNLVFD SLYDLITHYQ QVPLRCNEFE MRLSEPVPQT
NAHESKEWYH ASLTRAQAEH MLMRVPRDGA FLVRKRNEPN SYAISFRAEG KIKHCRVQQE
GQTVMLGNSE FDSLVDLISY YEKHPLYRKM KLRYPINEEA LEKIGTAEPD YGALYEGRNP
GFYVEANPMP TFKCAVKALF DYKAQREDEL TFTKSAIIQN VEKQEGGWWR GDYGGKKQLW
FPSNYVEEMV SPAALEPERE HLDENSPLGD LLRGVLDVPA CQIAVRPEGK NNRLFVFSIS
MASVAHWSLD VAADSQEELQ DWVKKIREVA QTADARLTEG KMMERRKKIA LELSELVVYC
RPVPFDEEKI GTERACYRDM SSFPETKAEK YVNKAKGKKF LQYNRLQLSR IYPKGQRLDS
SNYDPLPMWI CGSQLVALNF QTPDKPMQMN QALFLAGGHC GYVLQPSVMR DEAFDPFDKS
SLRGLEPCAI CIEVLGARHL PKNGRGIVCP FVEIEVAGAE YDSIKQKTEF VVDNGLNPVW
PAKPFHFQIS NPEFAFLRFV VYEEDMFSDQ NFLAQATFPV KGLKTGYRAV PLKNNYSEGL
ELASLLVKID VFPAKQENGD LSPFGGASLR ERSCDASGPL FHGRAREGSF EARYQQPFED
FRISQEHLAD HFDGRDRRTP RRTRVNGDNR L
