EFG1_CANAL
ID EFG1_CANAL Reviewed; 550 AA.
AC Q59X67; A0A1D8PTM1; Q59XB5;
DT 31-OCT-2012, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2017, sequence version 2.
DT 03-AUG-2022, entry version 101.
DE RecName: Full=Enhanced filamentous growth protein 1;
GN Name=EFG1; OrderedLocusNames=CAALFM_CR07890WA;
GN ORFNames=CaO19.610, CaO19.8243;
OS Candida albicans (strain SC5314 / ATCC MYA-2876) (Yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Debaryomycetaceae; Candida/Lodderomyces clade; Candida.
OX NCBI_TaxID=237561;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=15123810; DOI=10.1073/pnas.0401648101;
RA Jones T., Federspiel N.A., Chibana H., Dungan J., Kalman S., Magee B.B.,
RA Newport G., Thorstenson Y.R., Agabian N., Magee P.T., Davis R.W.,
RA Scherer S.;
RT "The diploid genome sequence of Candida albicans.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:7329-7334(2004).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=17419877; DOI=10.1186/gb-2007-8-4-r52;
RA van het Hoog M., Rast T.J., Martchenko M., Grindle S., Dignard D.,
RA Hogues H., Cuomo C., Berriman M., Scherer S., Magee B.B., Whiteway M.,
RA Chibana H., Nantel A., Magee P.T.;
RT "Assembly of the Candida albicans genome into sixteen supercontigs aligned
RT on the eight chromosomes.";
RL Genome Biol. 8:RESEARCH52.1-RESEARCH52.12(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND GENOME REANNOTATION.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=24025428; DOI=10.1186/gb-2013-14-9-r97;
RA Muzzey D., Schwartz K., Weissman J.S., Sherlock G.;
RT "Assembly of a phased diploid Candida albicans genome facilitates allele-
RT specific measurements and provides a simple model for repeat and indel
RT structure.";
RL Genome Biol. 14:RESEARCH97.1-RESEARCH97.14(2013).
RN [4]
RP FUNCTION.
RX PubMed=9298905; DOI=10.1016/s0092-8674(00)80358-x;
RA Lo H.J., Kohler J.R., DiDomenico B., Loebenberg D., Cacciapuoti A.,
RA Fink G.R.;
RT "Nonfilamentous C. albicans mutants are avirulent.";
RL Cell 90:939-949(1997).
RN [5]
RP FUNCTION.
RX PubMed=9846730; DOI=10.1099/00221287-144-11-2951;
RA Rademacher F., Kehren V., Stoldt V.R., Ernst J.F.;
RT "A Candida albicans chaperonin subunit (CaCct8p) as a suppressor of
RT morphogenesis and Ras phenotypes in C. albicans and Saccharomyces
RT cerevisiae.";
RL Microbiology 144:2951-2960(1998).
RN [6]
RP FUNCTION.
RX PubMed=10377153; DOI=10.1128/iai.67.7.3649-3652.1999;
RA Riggle P.J., Andrutis K.A., Chen X., Tzipori S.R., Kumamoto C.A.;
RT "Invasive lesions containing filamentous forms produced by a Candida
RT albicans mutant that is defective in filamentous growth in culture.";
RL Infect. Immun. 67:3649-3652(1999).
RN [7]
RP FUNCTION, AND INDUCTION.
RX PubMed=10456912; DOI=10.1128/iai.67.9.4655-4660.1999;
RA Sonneborn A., Tebarth B., Ernst J.F.;
RT "Control of white-opaque phenotypic switching in Candida albicans by the
RT Efg1p morphogenetic regulator.";
RL Infect. Immun. 67:4655-4660(1999).
RN [8]
RP FUNCTION, AND MUTAGENESIS OF THR-208.
RX PubMed=10496941; DOI=10.1128/iai.67.10.5514-5517.1999;
RA Sonneborn A., Bockmuhl D.P., Ernst J.F.;
RT "Chlamydospore formation in Candida albicans requires the Efg1p
RT morphogenetic regulator.";
RL Infect. Immun. 67:5514-5517(1999).
RN [9]
RP FUNCTION.
RX PubMed=10790384; DOI=10.1093/genetics/155.1.57;
RA Braun B.R., Johnson A.D.;
RT "TUP1, CPH1 and EFG1 make independent contributions to filamentation in
RT Candida albicans.";
RL Genetics 155:57-67(2000).
RN [10]
RP FUNCTION.
RX PubMed=10816502; DOI=10.1128/iai.68.6.3485-3490.2000;
RA Phan Q.T., Belanger P.H., Filler S.G.;
RT "Role of hyphal formation in interactions of Candida albicans with
RT endothelial cells.";
RL Infect. Immun. 68:3485-3490(2000).
RN [11]
RP FUNCTION.
RX PubMed=10692363; DOI=10.1128/jb.182.6.1580-1591.2000;
RA Srikantha T., Tsai L.K., Daniels K., Soll D.R.;
RT "EFG1 null mutants of Candida albicans switch but cannot express the
RT complete phenotype of white-phase budding cells.";
RL J. Bacteriol. 182:1580-1591(2000).
RN [12]
RP FUNCTION, MUTAGENESIS OF THR-208, AND PHOSPHORYLATION AT THR-208.
RX PubMed=11290709; DOI=10.1093/genetics/157.4.1523;
RA Bockmuhl D.P., Ernst J.F.;
RT "A potential phosphorylation site for an A-type kinase in the Efg1
RT regulator protein contributes to hyphal morphogenesis of Candida
RT albicans.";
RL Genetics 157:1523-1530(2001).
RN [13]
RP FUNCTION, AND DNA-BINDING.
RX PubMed=11395474; DOI=10.1128/jb.183.13.4090-4093.2001;
RA Leng P., Lee P.R., Wu H., Brown A.J.;
RT "Efg1, a morphogenetic regulator in Candida albicans, is a sequence-
RT specific DNA binding protein.";
RL J. Bacteriol. 183:4090-4093(2001).
RN [14]
RP FUNCTION.
RX PubMed=11595734; DOI=10.1074/jbc.m104484200;
RA Lane S., Birse C., Zhou S., Matson R., Liu H.;
RT "DNA array studies demonstrate convergent regulation of virulence factors
RT by Cph1, Cph2, and Efg1 in Candida albicans.";
RL J. Biol. Chem. 276:48988-48996(2001).
RN [15]
RP FUNCTION.
RX PubMed=12204378; DOI=10.1111/j.1574-6968.2002.tb11330.x;
RA Ramage G., VandeWalle K., Lopez-Ribot J.L., Wickes B.L.;
RT "The filamentation pathway controlled by the Efg1 regulator protein is
RT required for normal biofilm formation and development in Candida
RT albicans.";
RL FEMS Microbiol. Lett. 214:95-100(2002).
RN [16]
RP FUNCTION, AND INTERACTION WITH CZF1.
RX PubMed=11973327; DOI=10.1093/genetics/160.4.1749;
RA Giusani A.D., Vinces M., Kumamoto C.A.;
RT "Invasive filamentous growth of Candida albicans is promoted by Czf1p-
RT dependent relief of Efg1p-mediated repression.";
RL Genetics 160:1749-1753(2002).
RN [17]
RP FUNCTION.
RX PubMed=11796627; DOI=10.1128/iai.70.2.921-927.2002;
RA Staib P., Kretschmar M., Nichterlein T., Hof H., Morschhauser J.;
RT "Transcriptional regulators Cph1p and Efg1p mediate activation of the
RT Candida albicans virulence gene SAP5 during infection.";
RL Infect. Immun. 70:921-927(2002).
RN [18]
RP FUNCTION.
RX PubMed=12065511; DOI=10.1128/iai.70.7.3689-3700.2002;
RA Felk A., Kretschmar M., Albrecht A., Schaller M., Beinhauer S.,
RA Nichterlein T., Sanglard D., Korting H.C., Schafer W., Hube B.;
RT "Candida albicans hyphal formation and the expression of the Efg1-regulated
RT proteinases Sap4 to Sap6 are required for the invasion of parenchymal
RT organs.";
RL Infect. Immun. 70:3689-3700(2002).
RN [19]
RP FUNCTION.
RX PubMed=11832513; DOI=10.1099/00221287-148-2-497;
RA Dieterich C., Schandar M., Noll M., Johannes F.J., Brunner H., Graeve T.,
RA Rupp S.;
RT "In vitro reconstructed human epithelia reveal contributions of Candida
RT albicans EFG1 and CPH1 to adhesion and invasion.";
RL Microbiology 148:497-506(2002).
RN [20]
RP INDUCTION.
RX PubMed=12798685; DOI=10.1016/s0022-2836(03)00505-9;
RA Tebarth B., Doedt T., Krishnamurthy S., Weide M., Monterola F.,
RA Dominguez A., Ernst J.F.;
RT "Adaptation of the Efg1p morphogenetic pathway in Candida albicans by
RT negative autoregulation and PKA-dependent repression of the EFG1 gene.";
RL J. Mol. Biol. 329:949-962(2003).
RN [21]
RP FUNCTION.
RX PubMed=12492856; DOI=10.1046/j.1365-2958.2003.03300.x;
RA Sohn K., Urban C., Brunner H., Rupp S.;
RT "EFG1 is a major regulator of cell wall dynamics in Candida albicans as
RT revealed by DNA microarrays.";
RL Mol. Microbiol. 47:89-102(2003).
RN [22]
RP INDUCTION.
RX PubMed=12675809; DOI=10.1046/j.1365-2958.2003.t01-1-03448.x;
RA Lachke S.A., Srikantha T., Soll D.R.;
RT "The regulation of EFG1 in white-opaque switching in Candida albicans
RT involves overlapping promoters.";
RL Mol. Microbiol. 48:523-536(2003).
RN [23]
RP FUNCTION.
RX PubMed=15728931; DOI=10.1128/aac.49.3.1213-1215.2005;
RA Lo H.J., Wang J.S., Lin C.Y., Chen C.G., Hsiao T.Y., Hsu C.T., Su C.L.,
RA Fann M.J., Ching Y.T., Yang Y.L.;
RT "Efg1 involved in drug resistance by regulating the expression of ERG3 in
RT Candida albicans.";
RL Antimicrob. Agents Chemother. 49:1213-1215(2005).
RN [24]
RP FUNCTION.
RX PubMed=16487333; DOI=10.1111/j.1574-6968.2006.00109.x;
RA Saville S.P., Thomas D.P., Lopez Ribot J.L.;
RT "A role for Efg1p in Candida albicans interactions with extracellular
RT matrices.";
RL FEMS Microbiol. Lett. 256:151-158(2006).
RN [25]
RP FUNCTION, AND INTERACTION WITH FLO8.
RX PubMed=16267276; DOI=10.1091/mbc.e05-06-0502;
RA Cao F., Lane S., Raniga P.P., Lu Y., Zhou Z., Ramon K., Chen J., Liu H.;
RT "The Flo8 transcription factor is essential for hyphal development and
RT virulence in Candida albicans.";
RL Mol. Biol. Cell 17:295-307(2006).
RN [26]
RP FUNCTION.
RX PubMed=17880264; DOI=10.1371/journal.pbio.0050256;
RA Zordan R.E., Miller M.G., Galgoczy D.J., Tuch B.B., Johnson A.D.;
RT "Interlocking transcriptional feedback loops control white-opaque switching
RT in Candida albicans.";
RL PLoS Biol. 5:E256-E256(2007).
RN [27]
RP FUNCTION, DOMAIN, AND INTERACTION WITH CZF1 AND FLO8.
RX PubMed=18375615; DOI=10.1128/ec.00033-08;
RA Noffz C.S., Liedschulte V., Lengeler K., Ernst J.F.;
RT "Functional mapping of the Candida albicans Efg1 regulator.";
RL Eukaryot. Cell 7:881-893(2008).
RN [28]
RP FUNCTION.
RX PubMed=19346360; DOI=10.1128/aem.00098-09;
RA Stichternoth C., Ernst J.F.;
RT "Hypoxic adaptation by Efg1 regulates biofilm formation by Candida
RT albicans.";
RL Appl. Environ. Microbiol. 75:3663-3672(2009).
RN [29]
RP PHOSPHORYLATION AT THR-181, AND FUNCTION.
RX PubMed=19528234; DOI=10.1128/mcb.01502-08;
RA Wang A., Raniga P.P., Lane S., Lu Y., Liu H.;
RT "Hyphal chain formation in Candida albicans: Cdc28-Hgc1 phosphorylation of
RT Efg1 represses cell separation genes.";
RL Mol. Cell. Biol. 29:4406-4416(2009).
RN [30]
RP FUNCTION.
RX PubMed=19197361; DOI=10.1371/journal.ppat.1000294;
RA Bastidas R.J., Heitman J., Cardenas M.E.;
RT "The protein kinase Tor1 regulates adhesin gene expression in Candida
RT albicans.";
RL PLoS Pathog. 5:E1000294-E1000294(2009).
RN [31]
RP FUNCTION.
RX PubMed=20491944; DOI=10.1111/j.1567-1364.2010.00639.x;
RA Prasad T., Hameed S., Manoharlal R., Biswas S., Mukhopadhyay C.K.,
RA Goswami S.K., Prasad R.;
RT "Morphogenic regulator EFG1 affects the drug susceptibilities of pathogenic
RT Candida albicans.";
RL FEMS Yeast Res. 10:587-596(2010).
RN [32]
RP FUNCTION.
RX PubMed=20735781; DOI=10.1111/j.1365-2958.2010.07331.x;
RA Lohse M.B., Johnson A.D.;
RT "Temporal anatomy of an epigenetic switch in cell programming: the white-
RT opaque transition of C. albicans.";
RL Mol. Microbiol. 78:331-343(2010).
RN [33]
RP FUNCTION, DNA-BINDING, AND INDUCTION.
RX PubMed=21923768; DOI=10.1111/j.1365-2958.2011.07837.x;
RA Lassak T., Schneider E., Bussmann M., Kurtz D., Manak J.R., Srikantha T.,
RA Soll D.R., Ernst J.F.;
RT "Target specificity of the Candida albicans Efg1 regulator.";
RL Mol. Microbiol. 82:602-618(2011).
RN [34]
RP FUNCTION, AND INTERACTION WITH CZF1.
RX PubMed=22761849; DOI=10.1371/journal.pone.0039624;
RA Petrovska I., Kumamoto C.A.;
RT "Functional importance of the DNA binding activity of Candida albicans
RT Czf1p.";
RL PLoS ONE 7:E39624-E39624(2012).
CC -!- FUNCTION: Transcriptional regulator of the switch between 2 heritable
CC states, the white and opaque states. These 2 cell types differ in many
CC characteristics, including cell structure, mating competence, and
CC virulence. Each state is heritable for many generations, and switching
CC between states occurs stochastically, at low frequency. Antagonizes the
CC action of WOR1, WOR2 and CZF1, and promotes the white state. In white
CC cells, EFG1 represses WOR1 indirectly through WOR2 to maintain white
CC cell identity. Binds target gene promoters at the EFG1 recognition
CC sequence (EGRbox) TATGCATA. Acts as a major regulator of cell wall
CC dynamics and plays a role in interactions with extracellular matrices.
CC Required for TOR1-dependent cellular aggregation and adhesin
CC expression. Required for both normoxic and hypoxic biofilm formation.
CC Hypoxic biofilm formation is a major cause of perseverance and
CC antifungal resistance during infections. Contributes to virulence by
CC regulating hyphal formation and the factors that enable C.albicans to
CC invade and injure endothelial cells. Required for the formation of
CC thick-walled big resting spores called chlamydospores, which survive in
CC unfavorable conditions. Mediates the expression of virulence factors
CC SAP4, SAP5and SAP6 during infection. Involved in drug resistance by
CC regulating the expression of ERG3. {ECO:0000269|PubMed:10377153,
CC ECO:0000269|PubMed:10456912, ECO:0000269|PubMed:10496941,
CC ECO:0000269|PubMed:10692363, ECO:0000269|PubMed:10790384,
CC ECO:0000269|PubMed:10816502, ECO:0000269|PubMed:11290709,
CC ECO:0000269|PubMed:11395474, ECO:0000269|PubMed:11595734,
CC ECO:0000269|PubMed:11796627, ECO:0000269|PubMed:11832513,
CC ECO:0000269|PubMed:11973327, ECO:0000269|PubMed:12065511,
CC ECO:0000269|PubMed:12204378, ECO:0000269|PubMed:12492856,
CC ECO:0000269|PubMed:15728931, ECO:0000269|PubMed:16267276,
CC ECO:0000269|PubMed:16487333, ECO:0000269|PubMed:17880264,
CC ECO:0000269|PubMed:18375615, ECO:0000269|PubMed:19197361,
CC ECO:0000269|PubMed:19346360, ECO:0000269|PubMed:19528234,
CC ECO:0000269|PubMed:20491944, ECO:0000269|PubMed:20735781,
CC ECO:0000269|PubMed:21923768, ECO:0000269|PubMed:22761849,
CC ECO:0000269|PubMed:9298905, ECO:0000269|PubMed:9846730}.
CC -!- SUBUNIT: Interacts with CZF1 and FLO8. {ECO:0000269|PubMed:11973327,
CC ECO:0000269|PubMed:16267276, ECO:0000269|PubMed:18375615,
CC ECO:0000269|PubMed:22761849}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00630}.
CC -!- INDUCTION: Expression is specific for the white growth phase. Down-
CC regulation under hyphal induction depends on the presence of EFG1
CC itself which plays a role of autoinhibitor and the protein kinase A
CC isoforms TPK1 and TPK2. {ECO:0000269|PubMed:10456912,
CC ECO:0000269|PubMed:12675809, ECO:0000269|PubMed:12798685,
CC ECO:0000269|PubMed:21923768}.
CC -!- PTM: Thr-208 is a phosphorylation target to promote hyphal induction by
CC a subset of environmental cues. Phosphorylation at Thr-181 by the
CC CDc28/HGC1 complex represses cell separation genes and leads to hyphal
CC chain formation. {ECO:0000269|PubMed:11290709,
CC ECO:0000269|PubMed:19528234}.
CC -!- SIMILARITY: Belongs to the EFG1/PHD1/stuA family. {ECO:0000305}.
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DR EMBL; CP017630; AOW31479.1; -; Genomic_DNA.
DR RefSeq; XP_714237.2; XM_709144.2.
DR AlphaFoldDB; Q59X67; -.
DR SMR; Q59X67; -.
DR BioGRID; 1227239; 12.
DR STRING; 237561.Q59X67; -.
DR iPTMnet; Q59X67; -.
DR PRIDE; Q59X67; -.
DR GeneID; 3644145; -.
DR KEGG; cal:CAALFM_CR07890WA; -.
DR CGD; CAL0000201973; EFG1.
DR VEuPathDB; FungiDB:CR_07890W_A; -.
DR eggNOG; ENOG502QW2C; Eukaryota.
DR HOGENOM; CLU_032570_0_0_1; -.
DR InParanoid; Q59X67; -.
DR OrthoDB; 1357480at2759; -.
DR PHI-base; PHI:3505; -.
DR PHI-base; PHI:6671; -.
DR PHI-base; PHI:6801; -.
DR PHI-base; PHI:6805; -.
DR PRO; PR:Q59X67; -.
DR Proteomes; UP000000559; Chromosome R.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IBA:GO_Central.
DR GO; GO:0043565; F:sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR Gene3D; 3.10.260.10; -; 1.
DR InterPro; IPR029790; EFG1/Phd1/StuA.
DR InterPro; IPR036887; HTH_APSES_sf.
DR InterPro; IPR018004; KilA_N/APSES_HTH.
DR InterPro; IPR003163; Tscrpt_reg_HTH_APSES-type.
DR PANTHER; PTHR47792; PTHR47792; 1.
DR Pfam; PF04383; KilA-N; 1.
DR SMART; SM01252; KilA-N; 1.
DR SUPFAM; SSF54616; SSF54616; 1.
DR PROSITE; PS51299; HTH_APSES; 1.
PE 1: Evidence at protein level;
KW Cell adhesion; DNA-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Transcription; Transcription regulation; Virulence.
FT CHAIN 1..550
FT /note="Enhanced filamentous growth protein 1"
FT /id="PRO_0000420156"
FT DOMAIN 206..312
FT /note="HTH APSES-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00630"
FT DNA_BIND 240..261
FT /note="H-T-H motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00630"
FT REGION 17..48
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 72..95
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 123..182
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 329..435
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 476..550
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 123..161
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 346..435
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 476..544
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 181
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:19528234"
FT MOD_RES 208
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:11290709"
FT MUTAGEN 208
FT /note="T->A: Impairs chlamydospore formation and hypha
FT formation."
FT /evidence="ECO:0000269|PubMed:10496941,
FT ECO:0000269|PubMed:11290709"
FT MUTAGEN 208
FT /note="T->E: Impairs chlamydospore formation but causes
FT hyperfilamentation."
FT /evidence="ECO:0000269|PubMed:10496941,
FT ECO:0000269|PubMed:11290709"
SQ SEQUENCE 550 AA; 59612 MW; 777B4535B22EA81F CRC64;
MSTYSIPYYN QMNGNYNNGM PQQTTAANQQ AFPQQQQPTT TGNASQQQQQ AAATAAAAAV
QQPYNYMFYQ QQGQPGQQTG QTAGQQQQQQ QQQQQYDYNT YNRYQYPAAT SQGNYYQQTI
PNQLSQPQPQ HYNGSNRNYT SAPSGAPIPS NSTSGPSQQP PLPGQQAVPI PPHVSTMQQP
TPVQDTLNAS STSTVGQFQP PGIRPRVTTT MWEDEKTLCY QVDANNVSVV RRADNNMING
TKLLNVAQMT RGRRDGILKS EKVRHVVKIG SMHLKGVWIP FERALAMAQR EQIVDMLYPL
FVRDIKRVIQ TGVTPNAAAA TAAAAATATS ASAPPPPPPP VAAATTTAAT AISKSSSGNG
NSISATSGGS NVSGASGAGS TTSPVNTKAA TTAGTPQGNY YQTYNQQQYP QQYGQYNAPG
KNQNTPASQP GSTTNDQYLQ QQQQMYGYQS NYYQGGAANS SYYPNYYQQQ QPNYASSYPY
QQQQQKQQQQ QPNQQQQSDQ QQTSTPSGGA GTRSVHQSPQ VQSLTQGSVH PSPQQHQANQ
SASTVAKEEK
