ID AASS_RAT Reviewed; 926 AA.
AC A2VCW9;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 20-MAR-2007, sequence version 1.
DT 08-NOV-2023, entry version 96.
DE RecName: Full=Alpha-aminoadipic semialdehyde synthase, mitochondrial {ECO:0000250|UniProtKB:Q9UDR5};
DE AltName: Full=LKR/SDH {ECO:0000250|UniProtKB:Q9UDR5};
DE Includes:
DE RecName: Full=Lysine ketoglutarate reductase {ECO:0000250|UniProtKB:Q9UDR5};
DE Short=LKR {ECO:0000250|UniProtKB:Q9UDR5};
DE Short=LOR;
DE EC=1.5.1.8 {ECO:0000250|UniProtKB:Q9UDR5};
DE Includes:
DE RecName: Full=Saccharopine dehydrogenase {ECO:0000250|UniProtKB:Q9UDR5};
DE Short=SDH {ECO:0000250|UniProtKB:Q9UDR5};
DE EC=1.5.1.9 {ECO:0000250|UniProtKB:Q9UDR5};
DE Flags: Precursor;
GN Name=Aass {ECO:0000312|RGD:1310811};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1] {ECO:0000312|EMBL:AAI28772.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney {ECO:0000312|EMBL:AAI28772.1};
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).
CC -!- FUNCTION: Bifunctional enzyme that catalyzes the first two steps in
CC lysine degradation. {ECO:0000250|UniProtKB:Q9UDR5}.
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:0000250|UniProtKB:Q9UDR5};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:19375;
CC Evidence={ECO:0000250|UniProtKB:Q9UDR5};
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:0000250|UniProtKB:Q9UDR5};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24521;
CC Evidence={ECO:0000250|UniProtKB:Q9UDR5};
CC -!- PATHWAY: Amino-acid degradation; L-lysine degradation via saccharopine
CC pathway; glutaryl-CoA from L-lysine: step 1/6.
CC {ECO:0000250|UniProtKB:Q9UDR5}.
CC -!- PATHWAY: Amino-acid degradation; L-lysine degradation via saccharopine
CC pathway; glutaryl-CoA from L-lysine: step 2/6.
CC {ECO:0000250|UniProtKB:Q9UDR5}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:Q99K67}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:Q9UDR5}.
CC -!- DOMAIN: The N-terminal and the C-terminal domains contain respectively
CC the lysine ketoglutarate reductase and saccharopine dehydrogenase
CC activity. {ECO:0000250|UniProtKB:Q9UDR5}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the AlaDH/PNT family.
CC {ECO:0000255}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the saccharopine
CC dehydrogenase family. {ECO:0000255}.
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DR EMBL; BC128771; AAI28772.1; -; mRNA.
DR RefSeq; NP_001094433.1; NM_001100963.1.
DR AlphaFoldDB; A2VCW9; -.
DR SMR; A2VCW9; -.
DR STRING; 10116.ENSRNOP00000057271; -.
DR iPTMnet; A2VCW9; -.
DR PhosphoSitePlus; A2VCW9; -.
DR PaxDb; 10116-ENSRNOP00000057271; -.
DR PeptideAtlas; A2VCW9; -.
DR GeneID; 296925; -.
DR KEGG; rno:296925; -.
DR UCSC; RGD:1310811; rat.
DR AGR; RGD:1310811; -.
DR CTD; 10157; -.
DR RGD; 1310811; Aass.
DR eggNOG; KOG0172; Eukaryota.
DR InParanoid; A2VCW9; -.
DR OrthoDB; 2184985at2759; -.
DR PhylomeDB; A2VCW9; -.
DR Reactome; R-RNO-71064; Lysine catabolism.
DR UniPathway; UPA00868; UER00835.
DR UniPathway; UPA00868; UER00836.
DR PRO; PR:A2VCW9; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0047131; F:saccharopine dehydrogenase (NAD+, L-glutamate-forming) activity; ISS:UniProtKB.
DR GO; GO:0047130; F:saccharopine dehydrogenase (NADP+, L-lysine-forming) activity; ISS:UniProtKB.
DR GO; GO:0004753; F:saccharopine dehydrogenase activity; IBA:GO_Central.
DR GO; GO:0019477; P:L-lysine catabolic process; ISO:RGD.
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; ISS:UniProtKB.
DR CDD; cd12189; LKR_SDH_like; 1.
DR Gene3D; 1.10.1870.10; Domain 3, Saccharopine reductase; 1.
DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 3.
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 PANTHER; PTHR11133:SF25; ALPHA-AMINOADIPIC SEMIALDEHYDE SYNTHASE, MITOCHONDRIAL; 1.
DR PANTHER; PTHR11133; SACCHAROPINE DEHYDROGENASE; 1.
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; SSF52283; Formate/glycerate dehydrogenase catalytic domain-like; 1.
DR SUPFAM; SSF55347; Glyceraldehyde-3-phosphate dehydrogenase-like, C-terminal domain; 1.
DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1.
PE 2: Evidence at transcript 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_0000315868"
FT REGION 28..455
FT /note="Lysine-ketoglutarate reductase"
FT /evidence="ECO:0000250|UniProtKB:Q99K67"
FT REGION 477..926
FT /note="Saccharopine dehydrogenase"
FT /evidence="ECO:0000250|UniProtKB:Q99K67"
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:0000250|UniProtKB:Q99K67"
FT MOD_RES 52
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99K67"
FT MOD_RES 56
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99K67"
FT MOD_RES 93
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99K67"
FT MOD_RES 93
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99K67"
FT MOD_RES 128
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99K67"
FT MOD_RES 138
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99K67"
FT MOD_RES 138
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99K67"
FT MOD_RES 274
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99K67"
FT MOD_RES 286
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99K67"
FT MOD_RES 286
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99K67"
FT MOD_RES 333
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99K67"
FT MOD_RES 458
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99K67"
FT MOD_RES 458
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99K67"
FT MOD_RES 523
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99K67"
FT MOD_RES 523
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99K67"
FT MOD_RES 535
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99K67"
FT MOD_RES 535
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99K67"
FT MOD_RES 584
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99K67"
FT MOD_RES 584
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99K67"
FT MOD_RES 707
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99K67"
FT MOD_RES 732
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99K67"
FT MOD_RES 739
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99K67"
FT MOD_RES 761
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99K67"
FT MOD_RES 761
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99K67"
FT MOD_RES 778
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99K67"
FT MOD_RES 780
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99K67"
SQ SEQUENCE 926 AA; 102908 MW; 4350DDB240B4075F CRC64;
MLRAQRLRLA RLRACVSRGL HHKPVMALRR EDVNAWERRA PLAPKHIKGI TKLGYKVLIQ
PSNRRAIHDK EYVRAGGILQ EDITEACLIL GVKRPPEEKL MSKKTYAFFS HTIKAQEANM
SLLDEVLKQE IRLIDYEKMV DHRGSRIVAF GHWAGVAGMI NILHGMGLRL LALGHHTPFM
HLGMAHNYRN SSQAVQAVRD AGYEISLGLM PKSIGPLTFV FTGTGNVSKG AQEVFNELPC
EYVEPHELKE VSKTGDLRKV YGTVLSRHHH LVRKTDGVYD PVEYEKYPER YISRFNADIA
PYTTCLINGI YWEQNTPRLL TRQDAQSLLV PVKSSVVPVE GCPELPHKLV AICDISADTG
GSIDFMTECT TIERPFCMYD ADQHIIHDSV EGSGILMCSI DNLPAQLPIE ATEYFGDMLY
PYVEEMLLSD ASQPLESQNF SPVVRDAVIT SNGLLTDKYK YIQKLRESRE RIQFLSMSTK
KKVLVLGSGY VSGPVLEYLS RGNNIEITLG SDMTNQMQQL SKKYDINTVN VTVGKQEDKL
QSLVESQDLV ISLLPYVLHP VVAKACIDSK VNMVTASYIT PAMKELEKSV DDAGITVIGE
LGLDPGLDHM LAMETIDKAK DLGATIESYV SYCGGLPAPE HSDNPLRYKF SWSPVGVLMN
IMQPASYLLN GKVVNVTGGV SFLNSVTPMD YFPGLNLEGY PNRDSTKYAE IYGISSAHTL
LRGTLRYKGY SKALNGFVKL GLINRETYPA LRPEANPLTW KQLLCDLVGI SRSSSCEKLK
EVVFTKLGGD STQLEAAEWL GLLGDEQVPQ AESIVDAFSK HLVSKLSYGP EEKDMIVMRD
SFGIRHPSGH LENKTIDLVV YGDFNGFSAM AKTVGLPTAM AAKMLLDGEI ETKGLMGPFS
KEIYGPILER IKAEGIVFNT QSTIKL
//
