[1]	NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT), FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE. STRAIN=cv. Columbia; TISSUE=Seedling hypocotyl; DOI=10.1105/tpc.9.8.1305; PubMed=9286108 [NCBI, ExPASy, EBI, Israel, Japan] Tang G., Miron D., Zhu-Shimoni J.X., Galili G.; "Regulation of lysine catabolism through lysine-ketoglutarate reductase and saccharopine dehydrogenase in Arabidopsis."; Plant Cell 9:1305-1316(1997).
[2]	NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM LONG), AND FUNCTION. STRAIN=cv. Columbia, and cv. Landsberg erecta; DOI=10.1023/A:1005808923191; PubMed=9426595 [NCBI, ExPASy, EBI, Israel, Japan] Epelbaum S., McDevitt R., Falco S.C.; "Lysine-ketoglutarate reductase and saccharopine dehydrogenase from Arabidopsis thaliana: nucleotide sequence and characterization."; Plant Mol. Biol. 35:735-748(1997).
[3]	NUCLEOTIDE SEQUENCE [MRNA]. DOI=10.1104/pp.005660; PubMed=12226495 [NCBI, ExPASy, EBI, Israel, Japan] Tang G., Zhu X., Gakiere B., Levanony H., Kahana A., Galili G.; "The bifunctional LKR/SDH locus of plants also encodes a highly active monofunctional lysine-ketoglutarate reductase using a polyadenylation signal located within an intron."; Plant Physiol. 130:147-154(2002).
[4]	NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. STRAIN=cv. Columbia; DOI=10.1038/47134; PubMed=10617198 [NCBI, ExPASy, EBI, Israel, Japan] Mayer K.F.X., Schueller C., Wambutt R., Murphy G., Volckaert G., Pohl T., Duesterhoeft A., Stiekema W., Entian K.-D., Terryn N., Harris B., Ansorge W., Brandt P., Grivell L.A., Rieger M., Weichselgartner M., de Simone V., Obermaier B., Mache R., Mueller M., Kreis M., Delseny M., Puigdomenech P., Watson M., Schmidtheini T., Reichert B., Portetelle D., Perez-Alonso M., Boutry M., Bancroft I., Vos P., Hoheisel J., Zimmermann W., Wedler H., Ridley P., Langham S.-A., McCullagh B., Bilham L., Robben J., van der Schueren J., Grymonprez B., Chuang Y.-J., Vandenbussche F., Braeken M., Weltjens I., Voet M., Bastiaens I., Aert R., Defoor E., Weitzenegger T., Bothe G., Ramsperger U., Hilbert H., Braun M., Holzer E., Brandt A., Peters S., van Staveren M., Dirkse W., Mooijman P., Klein Lankhorst R., Rose M., Hauf J., Koetter P., Berneiser S., Hempel S., Feldpausch M., Lamberth S., Van den Daele H., De Keyser A., Buysshaert C., Gielen J., Villarroel R., De Clercq R., van Montagu M., Rogers J., Cronin A., Quail M.A., Bray-Allen S., Clark L., Doggett J., Hall S., Kay M., Lennard N., McLay K., Mayes R., Pettett A., Rajandream M.A., Lyne M., Benes V., Rechmann S., Borkova D., Bloecker H., Scharfe M., Grimm M., Loehnert T.-H., Dose S., de Haan M., Maarse A.C., Schaefer M., Mueller-Auer S., Gabel C., Fuchs M., Fartmann B., Granderath K., Dauner D., Herzl A., Neumann S., Argiriou A., Vitale D., Liguori R., Piravandi E., Massenet O., Quigley F., Clabauld G., Muendlein A., Felber R., Schnabl S., Hiller R., Schmidt W., Lecharny A., Aubourg S., Chefdor F., Cooke R., Berger C., Monfort A., Casacuberta E., Gibbons T., Weber N., Vandenbol M., Bargues M., Terol J., Torres A., Perez-Perez A., Purnelle B., Bent E., Johnson S., Tacon D., Jesse T., Heijnen L., Schwarz S., Scholler P., Heber S., Francs P., Bielke C., Frishman D., Haase D., Lemcke K., Mewes H.-W., Stocker S., Zaccaria P., Bevan M., Wilson R.K., de la Bastide M., Habermann K., Parnell L., Dedhia N., Gnoj L., Schutz K., Huang E., Spiegel L., Sekhon M., Murray J., Sheet P., Cordes M., Abu-Threideh J., Stoneking T., Kalicki J., Graves T., Harmon G., Edwards J., Latreille P., Courtney L., Cloud J., Abbott A., Scott K., Johnson D., Minx P., Bentley D., Fulton B., Miller N., Greco T., Kemp K., Kramer J., Fulton L., Mardis E., Dante M., Pepin K., Hillier L.W., Nelson J., Spieth J., Ryan E., Andrews S., Geisel C., Layman D., Du H., Ali J., Berghoff A., Jones K., Drone K., Cotton M., Joshu C., Antonoiu B., Zidanic M., Strong C., Sun H., Lamar B., Yordan C., Ma P., Zhong J., Preston R., Vil D., Shekher M., Matero A., Shah R., Swaby I.K., O'Shaughnessy A., Rodriguez M., Hoffman J., Till S., Granat S., Shohdy N., Hasegawa A., Hameed A., Lodhi M., Johnson A., Chen E., Marra M.A., Martienssen R., McCombie W.R.; "Sequence and analysis of chromosome 4 of the plant Arabidopsis thaliana."; Nature 402:769-777(1999).
[5]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 529-1064 (ISOFORM LONG). STRAIN=cv. Columbia; DOI=10.1126/science.1088305; PubMed=14593172 [NCBI, ExPASy, EBI, Israel, Japan] Yamada K., Lim J., Dale J.M., Chen H., Shinn P., Palm C.J., Southwick A.M., Wu H.C., Kim C.J., Nguyen M., Pham P.K., Cheuk R.F., Karlin-Newmann G., Liu S.X., Lam B., Sakano H., Wu T., Yu G., Miranda M., Quach H.L., Tripp M., Chang C.H., Lee J.M., Toriumi M.J., Chan M.M., Tang C.C., Onodera C.S., Deng J.M., Akiyama K., Ansari Y., Arakawa T., Banh J., Banno F., Bowser L., Brooks S.Y., Carninci P., Chao Q., Choy N., Enju A., Goldsmith A.D., Gurjal M., Hansen N.F., Hayashizaki Y., Johnson-Hopson C., Hsuan V.W., Iida K., Karnes M., Khan S., Koesema E., Ishida J., Jiang P.X., Jones T., Kawai J., Kamiya A., Meyers C., Nakajima M., Narusaka M., Seki M., Sakurai T., Satou M., Tamse R., Vaysberg M., Wallender E.K., Wong C., Yamamura Y., Yuan S., Shinozaki K., Davis R.W., Theologis A., Ecker J.R.; "Empirical analysis of transcriptional activity in the Arabidopsis genome."; Science 302:842-846(2003).
[6]	ALTERNATIVE INITIATION. DOI=10.1046/j.1365-313x.2000.00770.x; PubMed=10929113 [NCBI, ExPASy, EBI, Israel, Japan] Tang G., Zhu X., Tang X., Galili G.; "A novel composite locus of Arabidopsis encoding two polypeptides with metabolically related but distinct functions in lysine catabolism."; Plant J. 23:195-203(2000).
[7]	SUBCELLULAR LOCATION, AND BIOPHYSICOCHEMICAL PROPERTIES. DOI=10.1104/pp.124.3.1363; PubMed=11080311 [NCBI, ExPASy, EBI, Israel, Japan] Zhu X., Tang G., Galili G.; "Characterization of the two saccharopine dehydrogenase isozymes of lysine catabolism encoded by the single composite AtLKR/SDH locus of Arabidopsis."; Plant Physiol. 124:1363-1371(2000).
[8]	FUNCTION. DOI=10.1104/pp.126.4.1539; PubMed=11500552 [NCBI, ExPASy, EBI, Israel, Japan] Zhu X., Tang G., Granier F., Bouchez D., Galili G.; "A T-DNA insertion knockout of the bifunctional lysine-ketoglutarate reductase/saccharopine dehydrogenase gene elevates lysine levels in Arabidopsis seeds."; Plant Physiol. 126:1539-1545(2001).
[9]	ENZYME REGULATION, SUBUNIT, PHOSPHORYLATION AT THR-238 AND SER-458, AND MUTAGENESIS OF THR-238; SER-407; SER-458 AND 551-ASN--ARG-554. DOI=10.1074/jbc.M205466200; PubMed=12393892 [NCBI, ExPASy, EBI, Israel, Japan] Zhu X., Tang G., Galili G.; "The activity of the Arabidopsis bifunctional lysine-ketoglutarate reductase/saccharopine dehydrogenase enzyme of lysine catabolism is regulated by functional interaction between its two enzyme domains."; J. Biol. Chem. 277:49655-49661(2002).
[10]	INDUCTION. DOI=10.1104/pp.103.026294; PubMed=14576281 [NCBI, ExPASy, EBI, Israel, Japan] Stepansky A., Galili G.; "Synthesis of the Arabidopsis bifunctional lysine-ketoglutarate reductase/saccharopine dehydrogenase enzyme of lysine catabolism is concertedly regulated by metabolic and stress-associated signals."; Plant Physiol. 133:1407-1415(2003).
[11]	TISSUE SPECIFICITY, AND INDUCTION. DOI=10.1093/jxb/eri031; PubMed=15569707 [NCBI, ExPASy, EBI, Israel, Japan] Stepansky A., Yao Y., Tang G., Galili G.; "Regulation of lysine catabolism in Arabidopsis through concertedly regulated synthesis of the two distinct gene products of the composite AtLKR/SDH locus."; J. Exp. Bot. 56:525-536(2005).

Comments

FUNCTION: Bifunctional enzyme that catalyzes the first two steps in lysine degradation. The N-terminal and the C-terminal contain lysine-oxoglutarate reductase and saccharopine dehydrogenase activity, respectively. Negatively regulates free Lys accumulation in seeds.
CATALYTIC ACTIVITY: N⁶-(L-1,3-dicarboxypropyl)-L-lysine + NADP⁺ + H₂O = L-lysine + 2-oxoglutarate + NADPH.
CATALYTIC ACTIVITY: N⁶-(L-1,3-dicarboxypropyl)-L-lysine + NAD⁺ + H₂O = L-glutamate + 2-aminoadipate 6-semialdehyde + NADH.
ENZYME REGULATION: The LKR activity is stimulated by NaCl.

BIOPHYSICOCHEMICAL PROPERTIES:

Kinetic parameters:	K_M=5.180 mM for lysine (isoform Long at pH 7.5 and 30 degrees Celsius);
	K_M=0.272 mM for alpha-ketoglutarate (isoform Long at pH 7.5 and 30 degrees Celsius);
	K_M=0.044 mM for NADPH (isoform Long at pH 7.5 and 30 degrees Celsius);
	K_M=0.063 mM for saccharopine (isoform Long at pH 7 and 30 degrees Celsius);
	K_M=0.035 mM for saccharopine (isoform Long at pH 9 and 30 degrees Celsius);
	K_M=0.130 mM for saccharopine (isoform Short at pH 7 and 30 degrees Celsius);
	K_M=0.050 mM for saccharopine (isoform Short at pH 9 and 30 degrees Celsius);
	K_M=0.374 mM for NAD (isoform Long at pH 7 and 30 degrees Celsius);
	K_M=0.698 mM for NAD (isoform Long at pH 9 and 30 degrees Celsius);
	K_M=0.333 mM for NAD (isoform Short at pH 7 and 30 degrees Celsius);
	K_M=0.759 mM for NAD (isoform Short at pH 9 and 30 degrees Celsius);
pH dependence:	Optimum pH is 7.5 for LKR activity of isoform Long, and 9 for SDH activity of both isoforms Long and Short;

PATHWAY: Amino-acid degradation; L-lysine degradation via saccharopine pathway; glutaryl-CoA from L-lysine: step 1/6 .
PATHWAY: Amino-acid degradation; L-lysine degradation via saccharopine pathway; glutaryl-CoA from L-lysine: step 2/6 .
SUBUNIT: Homodimer.
SUBCELLULAR LOCATION: Cytoplasm.

ALTERNATIVE PRODUCTS: 2 named isoforms [FASTA] produced by alternative initiation.

Name	Long
Isoform ID	Q9SMZ4-1
Note: Contains both LKR and SDH activities.
This is the isoform sequence displayed in this entry.

Name	Short
Isoform ID	Q9SMZ4-2
Note: Contains only SDH activity.
Features which should be applied to build the isoform sequence: VSP_018641.

TISSUE SPECIFICITY: Ubiquitous, with higher levels in flowers. Isoform Long is mostly present in young leaves, cotyledons, root tips and mature root parts. Whereas isoform Short is mostly expressed in cotyledons and at low levels in all root parts.
DEVELOPMENTAL STAGE: In flowers, confined to ovules and vascular tissue of anther filament. In developing and mature seeds, expressed in embryo and the outer layers of the endosperm.
INDUCTION: Lysine, Sugar starvation, ABA and MeJA induce isoform Long, but not isoform Short (at protein level). Nitrogen starvation repress isoform Long, but not isoform Short (at protein level). Isoform Long and isoform Short are both slightly induced by NaCl and drought stress, but repressed by sugars.
PTM: Phosphorylation of Ser-458 seems important for the LKR activity.
SIMILARITY: In the N-terminal section; belongs to the AlaDH/PNT family.
SIMILARITY: In the C-terminal section; belongs to the saccharopine dehydrogenase family.
SEQUENCE CAUTION:
- Sequence=AAK97099.1; Type=Miscellaneous discrepancy; Note=Chimeric cDNA. Its C-terminal part is derived from gene At1G61240, which encoded for a protein of unknown function. Was originally thought to be an alternative splicing form of At4g33150

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

U90522; AAB53975.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
U90523; AAD00700.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
U95758; AAB96825.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
U95759; AAB96826.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF295389; AAK97099.1; ALT_SEQ; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AL035525; CAB36789.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AL161583; CAB80032.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AY039906; AAK64010.1; ALT_INIT; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AY094007; AAM16268.1; ALT_INIT; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

PIR

T05195; T05195.

3D structure databases

HSSP

Q9P4R4; 1FF9. [HSSP ENTRY / PDB]

ModBase

Q9SMZ4.

Organism-specific databases

TAIR

At4g33150; -.

Gene expression databases

ArrayExpress

Q9SMZ4; -.

GermOnline

AT4G33150; Arabidopsis thaliana.

Family and domain databases

InterPro

IPR007698; Ala_DHase/PNT_C.
IPR008142; Ala_DHase/PNT_CS1.
IPR008143; Ala_DHase/PNT_CS2.
IPR007886; Ala_DHase/PNT_N.
IPR007545; Saccharop_dh_N.
IPR005097; Saccharopine_DHase.
Graphical view of domain structure.

Pfam

PF01262; AlaDh_PNT_C; 1.
PF05222; AlaDh_PNT_N; 1.
PF03435; Saccharop_dh; 1.
PF04455; Saccharop_dh_N; 1.
Pfam graphical view of domain structure.

PROSITE

PS00836; ALADH_PNT_1; FALSE_NEG.
PS00837; ALADH_PNT_2; FALSE_NEG.

BLOCKS

Q9SMZ4.

Genome annotation databases

GenomeReviews

CT486007_GR; AT4G33150.

Other

ProtoNet

Q9SMZ4.

UniRef

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

Alternative initiation; Complete proteome; Cytoplasm; Multifunctional enzyme; NAD; NADP; Oxidoreductase; Phosphoprotein.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`CHAIN`	`1 1064`	`1064`	`Alpha-aminoadipic semialdehyde synthase.`	`PRO_0000226070`
`REGION`	`24 445`	`422`	`Lysine-ketoglutarate reductase.`
`REGION`	`583 1064`	`482`	`Saccharopine dehydrogenase.`
`MOD_RES`	`238 238`		`Phosphothreonine.`
`MOD_RES`	`458 458`		`Phosphoserine.`
`VAR_SEQ`	`1 582`		`Missing (in isoform Short).`	`VSP_018641`
`MUTAGEN`	`238 238`		`T->A,D: No effect on LKR and SDH activity.`
`MUTAGEN`	`407 407`		`S->A: No effect on LKR and SDH activity.`
`MUTAGEN`	`407 407`		`S->D: No LKR activity, but no effect on SDH activity.`
`MUTAGEN`	`458 458`		`S->A: Reduced LKR activity, but no effect on SDH activity.`
`MUTAGEN`	`458 458`		`S->D: No effect on LKR and SDH activity.`
`MUTAGEN`	`551 554`		`NEDY->IEGR: Loss of LKR activity stimulation by NaCl.`
`CONFLICT`	`167 169`		`KLI -> YLS (in Ref. 1, 2 and 3).`
`CONFLICT`	`324 324`		`R -> S (in Ref. 1 and 3).`
`CONFLICT`	`621 621`		`F -> V (in Ref. 5; AAK64010/AAM16268).`
`CONFLICT`	`715 715`		`K -> N (in Ref. 1; AAB53975/AAD00700).`
`CONFLICT`	`735 735`		`H -> P (in Ref. 1; AAB53975/AAD00700).`
`CONFLICT`	`739 739`		`M -> K (in Ref. 1; AAB53975/AAD00700).`
`CONFLICT`	`746 748`		`HIK -> PIT (in Ref. 1; AAB53975/AAD00700).`
`CONFLICT`	`765 765`		`P -> R (in Ref. 1; AAB53975/AAD00700).`
`CONFLICT`	`827 827`		`F -> L (in Ref. 2; AAB96825/AAB96826).`
`CONFLICT`	`1040 1040`		`L -> F (in Ref. 2; AAB96825).`

Sequence information

Length: 1064 AA [This is the length of the unprocessed precursor]

Molecular weight: 117149 Da [This is the MW of the unprocessed precursor]

CRC64: 6CA4EBDB22898C7E [This is a checksum on the sequence]

        10         20         30         40         50         60 
MNSNGHEEEK KLGNGVVGIL AETVNKWERR TPLTPSHCAR LLHGGKDRTG ISRIVVQPSA 

        70         80         90        100        110        120 
KRIHHDALYE DVGCEISDDL SDCGLILGIK QPELEMILPE RAYAFFSHTH KAQKENMPLL 

       130        140        150        160        170        180 
DKILSERVTL CDYELIVGDH GKRLLAFGKY AGRAGLVDFL HGLGQRKLIL GYSTPFLSLG 

       190        200        210        220        230        240 
ASYMYSSLAA AKAAVISVGE EIASQGLPLG ICPLVFVFTG TGNVSLGAQE IFKLLPHTFV 

       250        260        270        280        290        300 
EPSKLPELFV KDKGISQNGI STKRVYQVYG CIITSQDMVE HKDPSKSFDK ADYYAHPEHY 

       310        320        330        340        350        360 
NPVFHEKISP YTSVLVNCMY WEKRFPCLLS TKQLQDLTKK GLPLVGICDI TCDIGGSIEF 

       370        380        390        400        410        420 
VNRATLIDSP FFRFNPSNNS YYDDMDGDGV LCMAVDILPT EFAKEASQHF GDILSGFVGS 

       430        440        450        460        470        480 
LASMTEISDL PAHLKRACIS YRGELTSLYE YIPRMRKSNP EEAQDNIIAN GVSSQRTFNI 

       490        500        510        520        530        540 
LVSLSGHLFD KFLINEALDM IEAAGGSFHL AKCELGQSAD AESYSELEVG ADDKRVLDQI 

       550        560        570        580        590        600 
IDSLTRLANP NEDYISPHRE ANKISLKIGK VQQENEIKEK PEMTKKSGVL ILGAGRVCRP 

       610        620        630        640        650        660 
AADFLASVRT ISSQQWYKTY FGADSEEKTD VHVIVASLYL KDAKETVEGI SDVEAVRLDV 

       670        680        690        700        710        720 
SDSESLLKYV SQVDVVLSLL PASCHAVVAK TCIELKKHLV TASYVDDETS MLHEKAKSAG 

       730        740        750        760        770        780 
ITILGEMGLD PGIDHMMAMK MINDAHIKKG KVKSFTSYCG GLPSPAAANN PLAYKFSWNP 

       790        800        810        820        830        840 
AGAIRAGQNP AKYKSNGDII HVDGKNLYDS AARFRVPNLP AFALECFPNR DSLVYGEHYG 

       850        860        870        880        890        900 
IESEATTIFR GTLRYEGFSM IMATLSKLGF FDSEANQVLS TGKRITFGAL LSNILNKDAD 

       910        920        930        940        950        960 
NESEPLAGEE EISKRIIKLG HSKETAAKAA KTIVFLGFNE EREVPSLCKS VFDATCYLME 

       970        980        990       1000       1010       1020 
EKLAYSGNEQ DMVLLHHEVE VEFLESKRIE KHTATLLEFG DIKNGQTTTA MAKTVGIPAA 

      1030       1040       1050       1060 
IGALLLIEDK IKTRGVLRPL EAEVYLPALD ILQAYGIKLM EKAE

Q9SMZ4 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools