AASS_MOUSE
ID AASS_MOUSE Reviewed; 926 AA.
AC Q99K67; Q9Z1I9;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Alpha-aminoadipic semialdehyde synthase, mitochondrial {ECO:0000305|PubMed:10567240};
DE AltName: Full=LKR/SDH {ECO:0000305|PubMed:10567240};
DE Includes:
DE RecName: Full=Lysine ketoglutarate reductase {ECO:0000305|PubMed:10567240};
DE Short=LKR {ECO:0000303|PubMed:10567240};
DE Short=LOR {ECO:0000303|PubMed:10567240};
DE EC=1.5.1.8 {ECO:0000269|PubMed:10567240};
DE Includes:
DE RecName: Full=Saccharopine dehydrogenase {ECO:0000305|PubMed:10567240};
DE Short=SDH {ECO:0000303|PubMed:10567240};
DE EC=1.5.1.9 {ECO:0000269|PubMed:10567240};
DE Flags: Precursor;
GN Name=Aass {ECO:0000312|MGI:MGI:1353573}; Synonyms=Lorsdh;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, PATHWAY, SUBUNIT,
RP TISSUE SPECIFICITY, INDUCTION, DOMAIN, AND REGION.
RC STRAIN=C57BL/6J X CBA/J; TISSUE=Liver;
RX PubMed=10567240; DOI=10.1042/bj3440555;
RA Papes F., Kemper E.L., Cord-Neto G., Langone F., Arruda P.;
RT "Lysine degradation through the saccharopine pathway in mammals:
RT involvement of both bifunctional and monofunctional lysine-degrading
RT enzymes in mouse.";
RL Biochem. J. 344:555-563(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Liver, Pancreas, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-93; LYS-138; LYS-274; LYS-286;
RP LYS-333; LYS-458; LYS-523; LYS-535; LYS-584; LYS-732 AND LYS-761, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [5]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-48; LYS-52; LYS-56; LYS-93;
RP LYS-128; LYS-138; LYS-286; LYS-458; LYS-523; LYS-535; LYS-584; LYS-707;
RP LYS-739; LYS-761; LYS-778 AND LYS-780, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23576753; DOI=10.1073/pnas.1302961110;
RA Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B.,
RA Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.;
RT "Label-free quantitative proteomics of the lysine acetylome in mitochondria
RT identifies substrates of SIRT3 in metabolic pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013).
CC -!- FUNCTION: Bifunctional enzyme that catalyzes the first two steps in
CC lysine degradation. {ECO:0000269|PubMed:10567240}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + L-saccharopine + NADP(+) = 2-oxoglutarate + H(+) + L-
CC lysine + NADPH; Xref=Rhea:RHEA:19373, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16810, ChEBI:CHEBI:32551,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:57951, ChEBI:CHEBI:58349; EC=1.5.1.8;
CC Evidence={ECO:0000269|PubMed:10567240};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:19375;
CC Evidence={ECO:0000269|PubMed:10567240};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + L-saccharopine + NAD(+) = (S)-2-amino-6-oxohexanoate +
CC H(+) + L-glutamate + NADH; Xref=Rhea:RHEA:24520, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29985, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:57951, ChEBI:CHEBI:58321; EC=1.5.1.9;
CC Evidence={ECO:0000269|PubMed:10567240};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24521;
CC Evidence={ECO:0000269|PubMed:10567240};
CC -!- PATHWAY: Amino-acid degradation; L-lysine degradation via saccharopine
CC pathway; glutaryl-CoA from L-lysine: step 1/6.
CC {ECO:0000305|PubMed:10567240}.
CC -!- PATHWAY: Amino-acid degradation; L-lysine degradation via saccharopine
CC pathway; glutaryl-CoA from L-lysine: step 2/6.
CC {ECO:0000305|PubMed:10567240}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:10567240}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:Q9UDR5}.
CC -!- TISSUE SPECIFICITY: Highly expressed in kidney and liver, very low
CC expression is seen in heart, brain, spleen, lung, skeletal muscle and
CC testis. {ECO:0000269|PubMed:10567240}.
CC -!- INDUCTION: Induced by starvation. {ECO:0000269|PubMed:10567240}.
CC -!- DOMAIN: The N-terminal and the C-terminal domains contain respectively
CC the lysine ketoglutarate reductase and saccharopine dehydrogenase
CC activity. {ECO:0000303|PubMed:10567240}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the AlaDH/PNT family.
CC {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the saccharopine
CC dehydrogenase family. {ECO:0000305}.
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DR EMBL; AJ224761; CAA12114.1; -; mRNA.
DR EMBL; BC005420; AAH05420.1; -; mRNA.
DR CCDS; CCDS19937.1; -.
DR RefSeq; NP_038958.2; NM_013930.4.
DR AlphaFoldDB; Q99K67; -.
DR SMR; Q99K67; -.
DR BioGRID; 206032; 1.
DR STRING; 10090.ENSMUSP00000031707; -.
DR iPTMnet; Q99K67; -.
DR PhosphoSitePlus; Q99K67; -.
DR SwissPalm; Q99K67; -.
DR REPRODUCTION-2DPAGE; Q99K67; -.
DR jPOST; Q99K67; -.
DR MaxQB; Q99K67; -.
DR PaxDb; Q99K67; -.
DR PRIDE; Q99K67; -.
DR ProteomicsDB; 285627; -.
DR Antibodypedia; 17598; 203 antibodies from 25 providers.
DR DNASU; 30956; -.
DR Ensembl; ENSMUST00000031707; ENSMUSP00000031707; ENSMUSG00000029695.
DR GeneID; 30956; -.
DR KEGG; mmu:30956; -.
DR UCSC; uc009bbc.2; mouse.
DR CTD; 10157; -.
DR MGI; MGI:1353573; Aass.
DR VEuPathDB; HostDB:ENSMUSG00000029695; -.
DR eggNOG; KOG0172; Eukaryota.
DR GeneTree; ENSGT00390000013249; -.
DR HOGENOM; CLU_005231_0_1_1; -.
DR InParanoid; Q99K67; -.
DR OMA; KMEGRSE; -.
DR OrthoDB; 498994at2759; -.
DR PhylomeDB; Q99K67; -.
DR TreeFam; TF105728; -.
DR Reactome; R-MMU-71064; Lysine catabolism.
DR UniPathway; UPA00868; UER00835.
DR UniPathway; UPA00868; UER00836.
DR BioGRID-ORCS; 30956; 5 hits in 71 CRISPR screens.
DR PRO; PR:Q99K67; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q99K67; protein.
DR Bgee; ENSMUSG00000029695; Expressed in submandibular gland and 164 other tissues.
DR ExpressionAtlas; Q99K67; baseline and differential.
DR Genevisible; Q99K67; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; ISO:MGI.
DR GO; GO:0047131; F:saccharopine dehydrogenase (NAD+, L-glutamate-forming) activity; IDA:UniProtKB.
DR GO; GO:0047130; F:saccharopine dehydrogenase (NADP+, L-lysine-forming) activity; IDA:UniProtKB.
DR GO; GO:0004753; F:saccharopine dehydrogenase activity; IBA:GO_Central.
DR GO; GO:0006091; P:generation of precursor metabolites and energy; TAS:UniProtKB.
DR GO; GO:0019477; P:L-lysine catabolic process; IDA:MGI.
DR GO; GO:0033512; P:L-lysine catabolic process to acetyl-CoA via saccharopine; IEA:UniProtKB-UniPathway.
DR GO; GO:0019878; P:lysine biosynthetic process via aminoadipic acid; IBA:GO_Central.
DR GO; GO:0006554; P:lysine catabolic process; ISO:MGI.
DR InterPro; IPR007886; AlaDH/PNT_N.
DR InterPro; IPR007698; AlaDH/PNT_NAD(H)-bd.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR032095; Sacchrp_dh-like_C.
DR InterPro; IPR005097; Sacchrp_dh_NADP.
DR Pfam; PF05222; AlaDh_PNT_N; 1.
DR Pfam; PF16653; Sacchrp_dh_C; 1.
DR Pfam; PF03435; Sacchrp_dh_NADP; 1.
DR SMART; SM01002; AlaDh_PNT_C; 1.
DR SMART; SM01003; AlaDh_PNT_N; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 1: Evidence at protein level;
KW Acetylation; Mitochondrion; Multifunctional enzyme; NAD; NADP;
KW Oxidoreductase; Reference proteome; Transit peptide.
FT TRANSIT 1..27
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 28..926
FT /note="Alpha-aminoadipic semialdehyde synthase,
FT mitochondrial"
FT /id="PRO_0000001053"
FT REGION 28..455
FT /note="Lysine-ketoglutarate reductase"
FT /evidence="ECO:0000303|PubMed:10567240"
FT REGION 477..926
FT /note="Saccharopine dehydrogenase"
FT /evidence="ECO:0000303|PubMed:10567240"
FT BINDING 488
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q9UDR5"
FT BINDING 512
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q9UDR5"
FT BINDING 516
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q9UDR5"
FT BINDING 554
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q9UDR5"
FT BINDING 576
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q9UDR5"
FT BINDING 577..578
FT /ligand="L-saccharopine"
FT /ligand_id="ChEBI:CHEBI:57951"
FT /evidence="ECO:0000250|UniProtKB:Q9P4R4"
FT BINDING 577
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q9UDR5"
FT BINDING 603
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q9UDR5"
FT BINDING 604
FT /ligand="L-saccharopine"
FT /ligand_id="ChEBI:CHEBI:57951"
FT /evidence="ECO:0000250|UniProtKB:Q9P4R4"
FT BINDING 604
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q9UDR5"
FT BINDING 605
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q9UDR5"
FT BINDING 703
FT /ligand="L-saccharopine"
FT /ligand_id="ChEBI:CHEBI:57951"
FT /evidence="ECO:0000250|UniProtKB:Q9P4R4"
FT BINDING 724..726
FT /ligand="L-saccharopine"
FT /ligand_id="ChEBI:CHEBI:57951"
FT /evidence="ECO:0000250|UniProtKB:Q9P4R4"
FT MOD_RES 48
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 52
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 56
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 93
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 93
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 128
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 138
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 138
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 274
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 286
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 286
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 333
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 458
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 458
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 523
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 523
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 535
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 535
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 584
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 584
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 707
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 732
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 739
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 761
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 761
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 778
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 780
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT CONFLICT 198
FT /note="V -> I (in Ref. 1; CAA12114)"
FT /evidence="ECO:0000305"
FT CONFLICT 851
FT /note="L -> A (in Ref. 1; CAA12114)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 926 AA; 102975 MW; 5B4369C51F7D1D53 CRC64;
MLRAQRPRLA RLRACLSRGL HHKPVMALRR EDVNAWERRA PLAPKHIKGI TKLGYKVLIQ
PSNRRAIHDK EYVRAGGILQ EDITEACLIL GVKRPPEEKL MSKKTYAFFS HTIKAQEANM
NLLDEVLKQE IRLIDYEKMV DHRGSRIVAF GQWAGVAGMI NILHGMGLRL LALGHHTPFM
HLGMAHNYRN SSQAVQAVRD AGYEISLGLM PKSIGPLTFV FTGTGNVSKG AQEVFNELPC
EYVEPHELRE VSKTGDLRKV YGTVLSRHHH LVRKTDGVYD PVEYEKYPER YTSRFNTDIA
PYTTCLINGI YWEQNTPRLL TRQDAQSLLV PVKSSVVPVE GCPELPHKLV AICDISADTG
GSIDFMTECT TIERPFCMYD ADQQIIHDSV EGSGILMCSI DNLPAQLPIE ATEYFGDMLY
PYVEEMLLSD ASQPLESQNF SPVVRDAVIT SNGLLTDKYK YIQKLRESRE RIQFLSMSTK
KKVLVLGSGY VSGPVLEYLS RDNNIEITLG SDMTNQMQQL SKKYNINPVS LTVGKQEAKL
QSLVESQDLV ISLLPYVLHP VVAKACIESR VNMVTASYIT PAMKELEKSV DDAGITVIGE
LGLDPGLDHM LAMETIDTAK ELGATVESYV SYCGGLPAPE HSDNPLRYKF SWSPVGVLMN
IMQPASYLLN GKVVNVTGGV SFLNSVTPMD YFPGLNLEGY PNRDSIKYAE IYGISSAHTL
LRGTLRYKGY SKALNGFVKL GLINREAYPA LRPEANPLTW KQLLCDLVGI SRSSPCEKLK
EVVFTKLGGD NTQLEAAEWL GLLGDEQVPQ AESIVDAFSK HLVSKLSYGP EEKDMIVMRD
SFGIRHPSGH LENKTIDLVV YGDFNGFSAM AKTVGLPTAM AAKMLLDGEI EAKGLMGPFT
KEIYGPILER IKAEGIVFNT QSTIKL
