VPS34_YEAST
ID VPS34_YEAST Reviewed; 875 AA.
AC P22543; D6VYN8;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1991, sequence version 1.
DT 03-AUG-2022, entry version 202.
DE RecName: Full=Phosphatidylinositol 3-kinase VPS34;
DE Short=PI3-kinase VPS34;
DE Short=PI3K VPS34;
DE Short=PtdIns-3-kinase VPS34;
DE EC=2.7.1.137 {ECO:0000269|PubMed:7989323, ECO:0000269|PubMed:8385367};
DE AltName: Full=Carboxypeptidase Y-deficient protein 15;
DE AltName: Full=Vacuolar protein sorting-associated protein 34;
DE AltName: Full=Vacuolar protein-targeting protein 29;
GN Name=VPS34; Synonyms=END12, PEP15, VPL7, VPT29; OrderedLocusNames=YLR240W;
GN ORFNames=L9672.10;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RX PubMed=2247081; DOI=10.1128/mcb.10.12.6742-6754.1990;
RA Herman P.K., Emr S.D.;
RT "Characterization of VPS34, a gene required for vacuolar protein sorting
RT and vacuole segregation in Saccharomyces cerevisiae.";
RL Mol. Cell. Biol. 10:6742-6754(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169871;
RA Johnston M., Hillier L.W., Riles L., Albermann K., Andre B., Ansorge W.,
RA Benes V., Brueckner M., Delius H., Dubois E., Duesterhoeft A.,
RA Entian K.-D., Floeth M., Goffeau A., Hebling U., Heumann K.,
RA Heuss-Neitzel D., Hilbert H., Hilger F., Kleine K., Koetter P., Louis E.J.,
RA Messenguy F., Mewes H.-W., Miosga T., Moestl D., Mueller-Auer S.,
RA Nentwich U., Obermaier B., Piravandi E., Pohl T.M., Portetelle D.,
RA Purnelle B., Rechmann S., Rieger M., Rinke M., Rose M., Scharfe M.,
RA Scherens B., Scholler P., Schwager C., Schwarz S., Underwood A.P.,
RA Urrestarazu L.A., Vandenbol M., Verhasselt P., Vierendeels F., Voet M.,
RA Volckaert G., Voss H., Wambutt R., Wedler E., Wedler H., Zimmermann F.K.,
RA Zollner A., Hani J., Hoheisel J.D.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XII.";
RL Nature 387:87-90(1997).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [4]
RP FUNCTION.
RX PubMed=3062374; DOI=10.1128/mcb.8.11.4936-4948.1988;
RA Robinson J.S., Klionsky D.J., Banta L.M., Emr S.D.;
RT "Protein sorting in Saccharomyces cerevisiae: isolation of mutants
RT defective in the delivery and processing of multiple vacuolar hydrolases.";
RL Mol. Cell. Biol. 8:4936-4948(1988).
RN [5]
RP FUNCTION.
RX PubMed=2555343; DOI=10.1016/s0021-9258(19)47043-9;
RA Auger K.R., Carpenter C.L., Cantley L.C., Varticovski L.;
RT "Phosphatidylinositol 3-kinase and its novel product, phosphatidylinositol
RT 3-phosphate, are present in Saccharomyces cerevisiae.";
RL J. Biol. Chem. 264:20181-20184(1989).
RN [6]
RP FUNCTION, AND INTERACTION WITH VPS15.
RX PubMed=8387919; DOI=10.1002/j.1460-2075.1993.tb05867.x;
RA Stack J.H., Herman P.K., Schu P.V., Emr S.D.;
RT "A membrane-associated complex containing the Vps15 protein kinase and the
RT Vps34 PI 3-kinase is essential for protein sorting to the yeast lysosome-
RT like vacuole.";
RL EMBO J. 12:2195-2204(1993).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF ASP-731; ASN-736 AND
RP ASP-749.
RX PubMed=8385367; DOI=10.1126/science.8385367;
RA Schu P.V., Takegawa K., Fry M.J., Stack J.H., Waterfield M.D., Emr S.D.;
RT "Phosphatidylinositol 3-kinase encoded by yeast VPS34 gene essential for
RT protein sorting.";
RL Science 260:88-91(1993).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, AND AUTOPHOSPHORYLATION.
RX PubMed=7989323; DOI=10.1016/s0021-9258(18)31729-0;
RA Stack J.H., Emr S.D.;
RT "Vps34p required for yeast vacuolar protein sorting is a multiple
RT specificity kinase that exhibits both protein kinase and
RT phosphatidylinositol-specific PI 3-kinase activities.";
RL J. Biol. Chem. 269:31552-31562(1994).
RN [9]
RP FUNCTION.
RX PubMed=7929582; DOI=10.1083/jcb.127.2.373;
RA Munn A.L., Riezman H.;
RT "Endocytosis is required for the growth of vacuolar H(+)-ATPase-defective
RT yeast: identification of six new END genes.";
RL J. Cell Biol. 127:373-386(1994).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH VPS15; VPS30; VPS38
RP AND ATG14.
RX PubMed=11157979; DOI=10.1083/jcb.152.3.519;
RA Kihara A., Noda T., Ishihara N., Ohsumi Y.;
RT "Two distinct Vps34 phosphatidylinositol 3-kinase complexes function in
RT autophagy and carboxypeptidase Y sorting in Saccharomyces cerevisiae.";
RL J. Cell Biol. 152:519-530(2001).
RN [11]
RP FUNCTION.
RX PubMed=11523784; DOI=10.1007/s004380100510;
RA Takahashi T., Shimoi H., Ito K.;
RT "Identification of genes required for growth under ethanol stress using
RT transposon mutagenesis in Saccharomyces cerevisiae.";
RL Mol. Genet. Genomics 265:1112-1119(2001).
RN [12]
RP FUNCTION.
RX PubMed=12244127; DOI=10.1242/jcs.00090;
RA Burda P., Padilla S.M., Sarkar S., Emr S.D.;
RT "Retromer function in endosome-to-Golgi retrograde transport is regulated
RT by the yeast Vps34 PtdIns 3-kinase.";
RL J. Cell Sci. 115:3889-3900(2002).
RN [13]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=14562095; DOI=10.1038/nature02026;
RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA Weissman J.S., O'Shea E.K.;
RT "Global analysis of protein localization in budding yeast.";
RL Nature 425:686-691(2003).
RN [14]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE
RP AUTOPHAGY-SPECIFIC VPS34 PI3-KINASE COMPLEX I, AND INTERACTION WITH ATG38.
RX PubMed=24165940; DOI=10.1083/jcb.201304123;
RA Araki Y., Ku W.C., Akioka M., May A.I., Hayashi Y., Arisaka F.,
RA Ishihama Y., Ohsumi Y.;
RT "Atg38 is required for autophagy-specific phosphatidylinositol 3-kinase
RT complex integrity.";
RL J. Cell Biol. 203:299-313(2013).
RN [16]
RP DISRUPTION PHENOTYPE.
RX PubMed=26510498; DOI=10.1091/mbc.e15-08-0581;
RA Kim A., Cunningham K.W.;
RT "A LAPF/phafin1-like protein regulates TORC1 and lysosomal membrane
RT permeabilization in response to endoplasmic reticulum membrane stress.";
RL Mol. Biol. Cell 26:4631-4645(2015).
RN [17]
RP DISRUPTION PHENOTYPE.
RX PubMed=28483912; DOI=10.1128/mcb.00075-17;
RA Tanigawa M., Maeda T.;
RT "An In Vitro TORC1 Kinase Assay That Recapitulates the Gtr-Independent
RT Glutamine-Responsive TORC1 Activation Mechanism on Yeast Vacuoles.";
RL Mol. Cell. Biol. 37:e00075-e00075(2017).
RN [18]
RP DISRUPTION PHENOTYPE.
RX PubMed=29698392; DOI=10.1371/journal.pgen.1007334;
RA Ukai H., Araki Y., Kira S., Oikawa Y., May A.I., Noda T.;
RT "Gtr/Ego-independent TORC1 activation is achieved through a glutamine-
RT sensitive interaction with Pib2 on the vacuolar membrane.";
RL PLoS Genet. 14:e1007334-e1007334(2018).
CC -!- FUNCTION: Phosphatidylinositol 3-kinase required for cytoplasm to
CC vacuole transport (Cvt) and autophagy as a part of the autophagy-
CC specific VPS34 PI3-kinase complex I. This complex is essential to
CC recruit the ATG8-phosphatidylinositol conjugate and the ATG12-ATG5
CC conjugate to the pre-autophagosomal structure. Also involved in
CC endosome-to-Golgi retrograde transport as part of the VPS34 PI3-kinase
CC complex II. This second complex is required for the endosome-to-Golgi
CC retrieval of PEP1 and KEX2, and the recruitment of VPS5 and VPS7, two
CC components of the retromer complex, to endosomal membranes (probably
CC through the synthesis of a specific pool of phosphatidylinositol 3-
CC phosphate recruiting the retromer to the endosomes). Its activation by
CC VPS15 may lead to the phosphorylation of phosphatidylinositol in the
CC sorting compartment membrane. Finally, it might also be involved in
CC ethanol tolerance and cell wall integrity.
CC {ECO:0000269|PubMed:11157979, ECO:0000269|PubMed:11523784,
CC ECO:0000269|PubMed:12244127, ECO:0000269|PubMed:2247081,
CC ECO:0000269|PubMed:2555343, ECO:0000269|PubMed:3062374,
CC ECO:0000269|PubMed:7929582, ECO:0000269|PubMed:7989323,
CC ECO:0000269|PubMed:8385367, ECO:0000269|PubMed:8387919}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) + ATP = a
CC 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3-phosphate) + ADP +
CC H(+); Xref=Rhea:RHEA:12709, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:57880, ChEBI:CHEBI:58088, ChEBI:CHEBI:456216;
CC EC=2.7.1.137; Evidence={ECO:0000269|PubMed:7989323,
CC ECO:0000269|PubMed:8385367};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12710;
CC Evidence={ECO:0000305|PubMed:7989323, ECO:0000305|PubMed:8385367};
CC -!- ACTIVITY REGULATION: Phosphatidylinositol 3-kinase activity is directly
CC dependent on VPS15 protein kinase activity.
CC -!- SUBUNIT: Component of the autophagy-specific VPS34 PI3-kinase complex I
CC composed of VPS15, VPS30, VPS34, ATG14, AND ATG38; and of the VPS34
CC PI3-kinase complex II composed of VPS15, VPS30, VPS34 and VPS38.
CC Interacts directly with ATG38. {ECO:0000269|PubMed:11157979,
CC ECO:0000269|PubMed:24165940, ECO:0000269|PubMed:8387919}.
CC -!- INTERACTION:
CC P22543; Q05789: ATG38; NbExp=5; IntAct=EBI-20405, EBI-35873;
CC P22543; P08539: GPA1; NbExp=3; IntAct=EBI-20405, EBI-7376;
CC P22543; P22219: VPS15; NbExp=3; IntAct=EBI-20405, EBI-20347;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network membrane
CC {ECO:0000269|PubMed:11157979}; Peripheral membrane protein
CC {ECO:0000269|PubMed:11157979}. Endosome membrane
CC {ECO:0000269|PubMed:11157979}; Peripheral membrane protein
CC {ECO:0000269|PubMed:11157979}.
CC -!- PTM: Autophosphorylated. Might also be phosphorylated by VPS15.
CC -!- DISRUPTION PHENOTYPE: Abnormal localization of the peripheral membrane
CC protein PIB2 to the vacuolar membrane (PubMed:29698392,
CC PubMed:26510498). Decreases activation of TORC1 in response to
CC glutamine (PubMed:28483912). {ECO:0000269|PubMed:26510498,
CC ECO:0000269|PubMed:28483912, ECO:0000269|PubMed:29698392}.
CC -!- MISCELLANEOUS: Present with 1080 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the PI3/PI4-kinase family. {ECO:0000255|PROSITE-
CC ProRule:PRU00880}.
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DR EMBL; X53531; CAA37610.1; -; Genomic_DNA.
DR EMBL; U20865; AAB67396.1; -; Genomic_DNA.
DR EMBL; U19027; AAB67422.2; -; Genomic_DNA.
DR EMBL; BK006945; DAA09554.1; -; Genomic_DNA.
DR PIR; A36369; A36369.
DR RefSeq; NP_013341.1; NM_001182127.1.
DR PDB; 5DFZ; X-ray; 4.40 A; C=1-875.
DR PDB; 5KC2; EM; 28.00 A; C=1-875.
DR PDBsum; 5DFZ; -.
DR PDBsum; 5KC2; -.
DR AlphaFoldDB; P22543; -.
DR SMR; P22543; -.
DR BioGRID; 31507; 118.
DR ComplexPortal; CPX-1677; Phosphatidylinositol 3-kinase complex II.
DR ComplexPortal; CPX-1881; Phosphatidylinositol 3-kinase complex, class III, type I.
DR DIP; DIP-97N; -.
DR IntAct; P22543; 6.
DR MINT; P22543; -.
DR STRING; 4932.YLR240W; -.
DR iPTMnet; P22543; -.
DR MaxQB; P22543; -.
DR PaxDb; P22543; -.
DR PRIDE; P22543; -.
DR ABCD; P22543; 1 sequenced antibody.
DR EnsemblFungi; YLR240W_mRNA; YLR240W; YLR240W.
DR GeneID; 850941; -.
DR KEGG; sce:YLR240W; -.
DR SGD; S000004230; VPS34.
DR VEuPathDB; FungiDB:YLR240W; -.
DR eggNOG; KOG0906; Eukaryota.
DR GeneTree; ENSGT00940000156943; -.
DR HOGENOM; CLU_004869_0_0_1; -.
DR InParanoid; P22543; -.
DR OMA; GRQKCKI; -.
DR BioCyc; YEAST:YLR240W-MON; -.
DR BRENDA; 2.7.1.137; 984.
DR Reactome; R-SCE-1632852; Macroautophagy.
DR Reactome; R-SCE-1660514; Synthesis of PIPs at the Golgi membrane.
DR Reactome; R-SCE-1660516; Synthesis of PIPs at the early endosome membrane.
DR Reactome; R-SCE-1660517; Synthesis of PIPs at the late endosome membrane.
DR Reactome; R-SCE-5668599; RHO GTPases Activate NADPH Oxidases.
DR PRO; PR:P22543; -.
DR Proteomes; UP000002311; Chromosome XII.
DR RNAct; P22543; protein.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; HDA:SGD.
DR GO; GO:0005768; C:endosome; IDA:SGD.
DR GO; GO:0010008; C:endosome membrane; IC:ComplexPortal.
DR GO; GO:0000329; C:fungal-type vacuole membrane; IDA:SGD.
DR GO; GO:0000139; C:Golgi membrane; IC:ComplexPortal.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0071561; C:nucleus-vacuole junction; IDA:SGD.
DR GO; GO:0005777; C:peroxisome; IDA:SGD.
DR GO; GO:0000407; C:phagophore assembly site; IDA:SGD.
DR GO; GO:0034045; C:phagophore assembly site membrane; IC:ComplexPortal.
DR GO; GO:0034271; C:phosphatidylinositol 3-kinase complex, class III, type I; IDA:SGD.
DR GO; GO:0034272; C:phosphatidylinositol 3-kinase complex, class III, type II; IDA:SGD.
DR GO; GO:0016303; F:1-phosphatidylinositol-3-kinase activity; IDA:SGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0052742; F:phosphatidylinositol kinase activity; IBA:GO_Central.
DR GO; GO:0004672; F:protein kinase activity; IDA:SGD.
DR GO; GO:0000045; P:autophagosome assembly; IBA:GO_Central.
DR GO; GO:0006914; P:autophagy; IDA:ComplexPortal.
DR GO; GO:0030242; P:autophagy of peroxisome; IMP:SGD.
DR GO; GO:0006897; P:endocytosis; IBA:GO_Central.
DR GO; GO:0045324; P:late endosome to vacuole transport; IC:ComplexPortal.
DR GO; GO:0016236; P:macroautophagy; IMP:SGD.
DR GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; IDA:SGD.
DR GO; GO:0036092; P:phosphatidylinositol-3-phosphate biosynthetic process; IBA:GO_Central.
DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; IBA:GO_Central.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0016239; P:positive regulation of macroautophagy; IMP:SGD.
DR GO; GO:0032968; P:positive regulation of transcription elongation from RNA polymerase II promoter; IMP:SGD.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:2001159; P:regulation of protein localization by the Cvt pathway; IMP:SGD.
DR Gene3D; 1.10.1070.11; -; 1.
DR Gene3D; 1.25.40.70; -; 1.
DR Gene3D; 2.60.40.150; -; 1.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000403; PI3/4_kinase_cat_dom.
DR InterPro; IPR036940; PI3/4_kinase_cat_sf.
DR InterPro; IPR018936; PI3/4_kinase_CS.
DR InterPro; IPR002420; PI3K-type_C2_dom.
DR InterPro; IPR001263; PI3K_accessory_dom.
DR InterPro; IPR042236; PI3K_accessory_sf.
DR InterPro; IPR008290; PI3K_Vps34.
DR InterPro; IPR015433; PI_Kinase.
DR PANTHER; PTHR10048; PTHR10048; 1.
DR Pfam; PF00454; PI3_PI4_kinase; 1.
DR Pfam; PF00792; PI3K_C2; 1.
DR Pfam; PF00613; PI3Ka; 1.
DR PIRSF; PIRSF000587; PI3K_Vps34; 1.
DR SMART; SM00142; PI3K_C2; 1.
DR SMART; SM00145; PI3Ka; 1.
DR SMART; SM00146; PI3Kc; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR SUPFAM; SSF49562; SSF49562; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51547; C2_PI3K; 1.
DR PROSITE; PS00915; PI3_4_KINASE_1; 1.
DR PROSITE; PS00916; PI3_4_KINASE_2; 1.
DR PROSITE; PS50290; PI3_4_KINASE_3; 1.
DR PROSITE; PS51545; PIK_HELICAL; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Autophagy; Endosome; Golgi apparatus; Kinase;
KW Membrane; Nucleotide-binding; Phosphoprotein; Protein transport;
KW Reference proteome; Transferase; Transport.
FT CHAIN 1..875
FT /note="Phosphatidylinositol 3-kinase VPS34"
FT /id="PRO_0000088818"
FT DOMAIN 14..188
FT /note="C2 PI3K-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00880"
FT DOMAIN 293..526
FT /note="PIK helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00878"
FT DOMAIN 593..859
FT /note="PI3K/PI4K catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 599..605
FT /note="G-loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 728..736
FT /note="Catalytic loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 747..768
FT /note="Activation loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT MUTAGEN 731
FT /note="D->A: Loss of kinase activity and no vacuolar
FT carboxypeptidase Y (PCR1) sorting to the vacuole."
FT /evidence="ECO:0000269|PubMed:8385367"
FT MUTAGEN 736
FT /note="N->K: Loss of kinase activity and no vacuolar
FT carboxypeptidase Y (PCR1) sorting to the vacuole."
FT /evidence="ECO:0000269|PubMed:8385367"
FT MUTAGEN 749
FT /note="D->E: Loss of kinase activity and no vacuolar
FT carboxypeptidase Y (PCR1) sorting to the vacuole."
FT /evidence="ECO:0000269|PubMed:8385367"
SQ SEQUENCE 875 AA; 100921 MW; 806E3404EF260287 CRC64;
MSLNNITFCV SQDLDVPLKV KIKSLEGHKP LLKPSQKILN PELMLIGSNV FPSSDLIVSL
QVFDKERNRN LTLPIYTPYI PFRNSRTWDY WLTLPIRIKQ LTFSSHLRII LWEYNGSKQI
PFFNLETSIF NLKDCTLKRG FESLKFRYDV IDHCEVVTDN KDQENLNKYF QGEFTRLPWL
DEITISKLRK QRENRTWPQG TFVLNLEFPM LELPVVFIER EIMNTQMNIP TLKNNPGLST
DLREPNRNDP QIKISLGDKY HSTLKFYDPD QPNNDPIEEK YRRLERASKN ANLDKQVKPD
IKKRDYLNKI INYPPGTKLT AHEKGSIWKY RYYLMNNKKA LTKLLQSTNL REESERVEVL
ELMDSWAEID IDDALELLGS TFKNLSVRSY AVNRLKKASD KELELYLLQL VEAVCFENLS
TFSDKSNSEF TIVDAVSSQK LSGDSMLLST SHANQKLLKS ISSESETSGT ESLPIVISPL
AEFLIRRALV NPRLGSFFYW YLKSESEDKP YLDQILSSFW SRLDKKSRNI LNDQVRLINV
LRECCETIKR LKDTTAKKME LLVHLLETKV RPLVKVRPIA LPLDPDVLIC DVCPETSKVF
KSSLSPLKIT FKTTLNQPYH LMFKVGDDLR QDQLVVQIIS LMNELLKNEN VDLKLTPYKI
LATGPQEGAI EFIPNDTLAS ILSKYHGILG YLKLHYPDEN ATLGVQGWVL DNFVKSCAGY
CVITYILGVG DRHLDNLLVT PDGHFFHADF GYILGQDPKP FPPLMKLPPQ IIEAFGGAES
SNYDKFRSYC FVAYSILRRN AGLILNLFEL MKTSNIPDIR IDPNGAILRV RERFNLNMSE
EDATVHFQNL INDSVNALLP IVIDHLHNLA QYWRT
