LYS2_YEAST
ID LYS2_YEAST Reviewed; 1392 AA.
AC P07702; D6VQB4;
DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-1992, sequence version 2.
DT 03-AUG-2022, entry version 205.
DE RecName: Full=L-2-aminoadipate reductase;
DE EC=1.2.1.31 {ECO:0000269|PubMed:10320345};
DE EC=1.2.1.95 {ECO:0000269|PubMed:10320345};
DE AltName: Full=Alpha-aminoadipate reductase {ECO:0000303|PubMed:10320345};
DE Short=Alpha-AR;
DE AltName: Full=L-aminoadipate-semialdehyde dehydrogenase;
GN Name=LYS2; OrderedLocusNames=YBR115C; ORFNames=YBR0910;
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].
RX PubMed=2013406; DOI=10.1016/0378-1119(91)90117-t;
RA Morris M.E., Jinks-Robertson S.;
RT "Nucleotide sequence of the LYS2 gene of Saccharomyces cerevisiae: homology
RT to Bacillus brevis tyrocidine synthetase 1.";
RL Gene 98:141-145(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=7900426; DOI=10.1002/yea.320101014;
RA Mannhaupt G., Stucka R., Ehnle S., Vetter I., Feldmann H.;
RT "Analysis of a 70 kb region on the right arm of yeast chromosome II.";
RL Yeast 10:1363-1381(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=7813418; DOI=10.1002/j.1460-2075.1994.tb06923.x;
RA Feldmann H., Aigle M., Aljinovic G., Andre B., Baclet M.C., Barthe C.,
RA Baur A., Becam A.-M., Biteau N., Boles E., Brandt T., Brendel M.,
RA Brueckner M., Bussereau F., Christiansen C., Contreras R., Crouzet M.,
RA Cziepluch C., Demolis N., Delaveau T., Doignon F., Domdey H.,
RA Duesterhus S., Dubois E., Dujon B., El Bakkoury M., Entian K.-D.,
RA Feuermann M., Fiers W., Fobo G.M., Fritz C., Gassenhuber J., Glansdorff N.,
RA Goffeau A., Grivell L.A., de Haan M., Hein C., Herbert C.J.,
RA Hollenberg C.P., Holmstroem K., Jacq C., Jacquet M., Jauniaux J.-C.,
RA Jonniaux J.-L., Kallesoee T., Kiesau P., Kirchrath L., Koetter P.,
RA Korol S., Liebl S., Logghe M., Lohan A.J.E., Louis E.J., Li Z.Y.,
RA Maat M.J., Mallet L., Mannhaupt G., Messenguy F., Miosga T., Molemans F.,
RA Mueller S., Nasr F., Obermaier B., Perea J., Pierard A., Piravandi E.,
RA Pohl F.M., Pohl T.M., Potier S., Proft M., Purnelle B., Ramezani Rad M.,
RA Rieger M., Rose M., Schaaff-Gerstenschlaeger I., Scherens B.,
RA Schwarzlose C., Skala J., Slonimski P.P., Smits P.H.M., Souciet J.-L.,
RA Steensma H.Y., Stucka R., Urrestarazu L.A., van der Aart Q.J.M.,
RA Van Dyck L., Vassarotti A., Vetter I., Vierendeels F., Vissers S.,
RA Wagner G., de Wergifosse P., Wolfe K.H., Zagulski M., Zimmermann F.K.,
RA Mewes H.-W., Kleine K.;
RT "Complete DNA sequence of yeast chromosome II.";
RL EMBO J. 13:5795-5809(1994).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-150 AND 1209-1392.
RX PubMed=3542721; DOI=10.1016/0378-1119(86)90408-7;
RA Fleig U.N., Pridmore R.D., Philippsen P.;
RT "Construction of LYS2 cartridges for use in genetic manipulations of
RT Saccharomyces cerevisiae.";
RL Gene 46:237-245(1986).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1083-1392.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=1626431; DOI=10.1002/yea.320080507;
RA Mannhaupt G., Stucka R., Ehnle S., Vetter I., Feldmann H.;
RT "Molecular analysis of yeast chromosome II between CMD1 and LYS2: the
RT excision repair gene RAD16 located in this region belongs to a novel group
RT of double-finger proteins.";
RL Yeast 8:397-408(1992).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-130.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=7916691; DOI=10.1111/j.1432-1033.1993.tb18268.x;
RA Schaaff-Gerstenschlaeger I., Mannhaupt G., Vetter I., Zimmermann F.K.,
RA Feldmann H.;
RT "TKL2, a second transketolase gene of Saccharomyces cerevisiae. Cloning,
RT sequence and deletion analysis of the gene.";
RL Eur. J. Biochem. 217:487-492(1993).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, PHOSPHOPANTETHEINYLATION AT SER-880,
RP IDENTIFICATION BY MASS SPECTROMETRY, SUBSTRATE SPECIFICITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND REACTION MECHANISM.
RX PubMed=10320345; DOI=10.1021/bi9829940;
RA Ehmann D.E., Gehring A.M., Walsh C.T.;
RT "Lysine biosynthesis in Saccharomyces cerevisiae: mechanism of alpha-
RT aminoadipate reductase (Lys2) involves posttranslational
RT phosphopantetheinylation by Lys5.";
RL Biochemistry 38:6171-6177(1999).
RN [9]
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 [10]
RP UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-541 AND LYS-1276, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22106047; DOI=10.1002/pmic.201100166;
RA Starita L.M., Lo R.S., Eng J.K., von Haller P.D., Fields S.;
RT "Sites of ubiquitin attachment in Saccharomyces cerevisiae.";
RL Proteomics 12:236-240(2012).
CC -!- FUNCTION: Catalyzes the activation of alpha-aminoadipate by ATP-
CC dependent adenylation and the reduction of activated alpha-aminoadipate
CC by NADPH. The activated alpha-aminoadipate is bound to the
CC phosphopantheinyl group of the enzyme itself before it is reduced to
CC (S)-2-amino-6-oxohexanoate. {ECO:0000269|PubMed:10320345}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-2-amino-6-oxohexanoate + H2O + NADP(+) = 2 H(+) + L-2-
CC aminoadipate + NADPH; Xref=Rhea:RHEA:12304, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58321,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:58672; EC=1.2.1.31;
CC Evidence={ECO:0000269|PubMed:10320345};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-2-amino-6-oxohexanoate + H2O + NAD(+) = 2 H(+) + L-2-
CC aminoadipate + NADH; Xref=Rhea:RHEA:12308, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:58321, ChEBI:CHEBI:58672; EC=1.2.1.31;
CC Evidence={ECO:0000269|PubMed:10320345};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-2-amino-6-oxohexanoate + AMP + diphosphate + NADP(+) = ATP
CC + H(+) + L-2-aminoadipate + NADPH; Xref=Rhea:RHEA:46936,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58321, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:58672, ChEBI:CHEBI:456215; EC=1.2.1.95;
CC Evidence={ECO:0000269|PubMed:10320345};
CC -!- COFACTOR:
CC Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC Evidence={ECO:0000269|PubMed:10320345};
CC Note=Binds 1 phosphopantetheine covalently.
CC {ECO:0000269|PubMed:10320345};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=620 uM for NADPH {ECO:0000269|PubMed:10320345};
CC Note=kcat is 670 min(-1). {ECO:0000269|PubMed:10320345};
CC -!- PATHWAY: Amino-acid biosynthesis; L-lysine biosynthesis via AAA
CC pathway; L-lysine from L-alpha-aminoadipate (fungal route): step 1/3.
CC -!- MISCELLANEOUS: Present with 7430 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC {ECO:0000305}.
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DR EMBL; M36287; AAA34747.1; -; Genomic_DNA.
DR EMBL; X66247; CAA46975.1; -; Genomic_DNA.
DR EMBL; X78993; CAA55617.1; -; Genomic_DNA.
DR EMBL; Z35984; CAA85072.1; -; Genomic_DNA.
DR EMBL; X73532; CAA51938.1; -; Genomic_DNA.
DR EMBL; BK006936; DAA07234.1; -; Genomic_DNA.
DR PIR; JU0448; YGBYAD.
DR RefSeq; NP_009673.1; NM_001178463.1.
DR AlphaFoldDB; P07702; -.
DR SMR; P07702; -.
DR BioGRID; 32818; 27.
DR DIP; DIP-6811N; -.
DR IntAct; P07702; 4.
DR MINT; P07702; -.
DR STRING; 4932.YBR115C; -.
DR CarbonylDB; P07702; -.
DR iPTMnet; P07702; -.
DR MaxQB; P07702; -.
DR PaxDb; P07702; -.
DR PRIDE; P07702; -.
DR EnsemblFungi; YBR115C_mRNA; YBR115C; YBR115C.
DR GeneID; 852412; -.
DR KEGG; sce:YBR115C; -.
DR SGD; S000000319; LYS2.
DR VEuPathDB; FungiDB:YBR115C; -.
DR eggNOG; KOG1178; Eukaryota.
DR HOGENOM; CLU_000022_19_0_1; -.
DR InParanoid; P07702; -.
DR OMA; ENDKFTM; -.
DR BioCyc; MetaCyc:YBR115C-MON; -.
DR BioCyc; YEAST:YBR115C-MON; -.
DR BRENDA; 1.2.1.95; 984.
DR SABIO-RK; P07702; -.
DR UniPathway; UPA00033; UER00032.
DR PRO; PR:P07702; -.
DR Proteomes; UP000002311; Chromosome II.
DR RNAct; P07702; protein.
DR GO; GO:0005737; C:cytoplasm; NAS:SGD.
DR GO; GO:0004043; F:L-aminoadipate-semialdehyde dehydrogenase activity; IDA:SGD.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0019878; P:lysine biosynthetic process via aminoadipic acid; IDA:SGD.
DR CDD; cd05235; SDR_e1; 1.
DR Gene3D; 1.10.1200.10; -; 1.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 3.40.50.12780; -; 1.
DR InterPro; IPR010071; AA_adenyl_domain.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR045851; AMP-bd_C_sf.
DR InterPro; IPR020845; AMP-binding_CS.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
DR InterPro; IPR042099; ANL_N_sf.
DR InterPro; IPR013120; Far_NAD-bd.
DR InterPro; IPR014397; Lys2.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR010080; Thioester_reductase-like_dom.
DR Pfam; PF00501; AMP-binding; 1.
DR Pfam; PF07993; NAD_binding_4; 1.
DR Pfam; PF00550; PP-binding; 1.
DR SMART; SM00823; PKS_PP; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR TIGRFAMs; TIGR01733; AA-adenyl-dom; 1.
DR TIGRFAMs; TIGR03443; alpha_am_amid; 1.
DR TIGRFAMs; TIGR01746; Thioester-redct; 1.
DR PROSITE; PS00455; AMP_BINDING; 1.
DR PROSITE; PS50075; CARRIER; 1.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 1: Evidence at protein level;
KW Amino-acid biosynthesis; Isopeptide bond; Lysine biosynthesis; NADP;
KW Oxidoreductase; Phosphopantetheine; Phosphoprotein; Reference proteome;
KW Ubl conjugation.
FT CHAIN 1..1392
FT /note="L-2-aminoadipate reductase"
FT /id="PRO_0000193153"
FT DOMAIN 843..920
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 880
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000269|PubMed:10320345"
FT CROSSLNK 541
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0007744|PubMed:22106047"
FT CROSSLNK 1276
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0007744|PubMed:22106047"
SQ SEQUENCE 1392 AA; 155346 MW; F0083A80BC6F7FB5 CRC64;
MTNEKVWIEK LDNPTLSVLP HDFLRPQQEP YTKQATYSLQ LPQLDVPHDS FSNKYAVALS
VWAALIYRVT GDDDIVLYIA NNKILRFNIQ PTWSFNELYS TINNELNKLN SIEANFSFDE
LAEKIQSCQD LERTPQLFRL AFLENQDFKL DEFKHHLVDF ALNLDTSNNA HVLNLIYNSL
LYSNERVTIV ADQFTQYLTA ALSDPSNCIT KISLITASSK DSLPDPTKNL GWCDFVGCIH
DIFQDNAEAF PERTCVVETP TLNSDKSRSF TYRDINRTSN IVAHYLIKTG IKRGDVVMIY
SSRGVDLMVC VMGVLKAGAT FSVIDPAYPP ARQTIYLGVA KPRGLIVIRA AGQLDQLVED
YINDELEIVS RINSIAIQEN GTIEGGKLDN GEDVLAPYDH YKDTRTGVVV GPDSNPTLSF
TSGSEGIPKG VLGRHFSLAY YFNWMSKRFN LTENDKFTML SGIAHDPIQR DMFTPLFLGA
QLYVPTQDDI GTPGRLAEWM SKYGCTVTHL TPAMGQLLTA QATTPFPKLH HAFFVGDILT
KRDCLRLQTL AENCRIVNMY GTTETQRAVS YFEVKSKNDD PNFLKKLKDV MPAGKGMLNV
QLLVVNRNDR TQICGIGEIG EIYVRAGGLA EGYRGLPELN KEKFVNNWFV EKDHWNYLDK
DNGEPWRQFW LGPRDRLYRT GDLGRYLPNG DCECCGRADD QVKIRGFRIE LGEIDTHISQ
HPLVRENITL VRKNADNEPT LITFMVPRFD KPDDLSKFQS DVPKEVETDP IVKGLIGYHL
LSKDIRTFLK KRLASYAMPS LIVVMDKLPL NPNGKVDKPK LQFPTPKQLN LVAENTVSET
DDSQFTNVER EVRDLWLSIL PTKPASVSPD DSFFDLGGHS ILATKMIFTL KKKLQVDLPL
GTIFKYPTIK AFAAEIDRIK SSGGSSQGEV VENVTANYAE DAKKLVETLP SSYPSREYFV
EPNSAEGKTT INVFVTGVTG FLGSYILADL LGRSPKNYSF KVFAHVRAKD EEAAFARLQK
AGITYGTWNE KFASNIKVVL GDLSKSQFGL SDEKWMDLAN TVDIIIHNGA LVHWVYPYAK
LRDPNVISTI NVMSLAAVGK PKFFDFVSST STLDTEYYFN LSDKLVSEGK PGILESDDLM
NSASGLTGGY GQSKWAAEYI IRRAGERGLR GCIVRPGYVT GASANGSSNT DDFLLRFLKG
SVQLGKIPDI ENSVNMVPVD HVARVVVATS LNPPKENELA VAQVTGHPRI LFKDYLYTLH
DYGYDVEIES YSKWKKSLEA SVIDRNEENA LYPLLHMVLD NLPESTKAPE LDDRNAVASL
KKDTAWTGVD WSNGIGVTPE EVGIYIAFLN KVGFLPPPTH NDKLPLPSIE LTQAQISLVA
SGAGARGSSA AA
