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Protein

Alpha-aminoadipic semialdehyde synthase, mitochondrial

Gene

AASS

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Bifunctional enzyme that catalyzes the first two steps in lysine degradation. The N-terminal and the C-terminal contain lysine-ketoglutarate reductase and saccharopine dehydrogenase activity, respectively.

Catalytic activityi

N6-(L-1,3-dicarboxypropyl)-L-lysine + NADP+ + H2O = L-lysine + 2-oxoglutarate + NADPH.
N6-(L-1,3-dicarboxypropyl)-L-lysine + NAD+ + H2O = L-glutamate + (S)-2-amino-6-oxohexanoate + NADH.

Pathwayi: L-lysine degradation via saccharopine pathway

This protein is involved in step 1 and 2 of the subpathway that synthesizes glutaryl-CoA from L-lysine.
Proteins known to be involved in the 6 steps of the subpathway in this organism are:
  1. Alpha-aminoadipic semialdehyde synthase, mitochondrial (AASS)
  2. Alpha-aminoadipic semialdehyde synthase, mitochondrial (AASS)
  3. no protein annotated in this organism
  4. Kynurenine/alpha-aminoadipate aminotransferase, mitochondrial (AADAT)
  5. no protein annotated in this organism
  6. Dihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex, mitochondrial (DLST), Dihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex (sucB)
This subpathway is part of the pathway L-lysine degradation via saccharopine pathway, which is itself part of Amino-acid degradation.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes glutaryl-CoA from L-lysine, the pathway L-lysine degradation via saccharopine pathway and in Amino-acid degradation.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei604SaccharopineBy similarity1
Binding sitei653NADP; via amide nitrogenBy similarity1
Binding sitei703SaccharopineBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi488 – 491NADPBy similarity4
Nucleotide bindingi603 – 605NADPBy similarity3

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionMultifunctional enzyme, Oxidoreductase
LigandNAD, NADP

Enzyme and pathway databases

BioCyciMetaCyc:HS00244-MONOMER
ReactomeiR-HSA-71064 Lysine catabolism
SABIO-RKiQ9UDR5
UniPathwayi
UPA00868;UER00835

UPA00868;UER00836

Names & Taxonomyi

Protein namesi
Recommended name:
Alpha-aminoadipic semialdehyde synthase, mitochondrial
Alternative name(s):
LKR/SDH
Including the following 2 domains:
Lysine ketoglutarate reductase (EC:1.5.1.8)
Short name:
LKR
Short name:
LOR
Saccharopine dehydrogenase (EC:1.5.1.9)
Short name:
SDH
Gene namesi
Name:AASS
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000008311.14
HGNCiHGNC:17366 AASS
MIMi605113 gene
neXtProtiNX_Q9UDR5

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Involvement in diseasei

Hyperlysinemia, 1 (HYPLYS1)1 Publication
The disease is caused by mutations affecting the gene represented in this entry. In hyperlysinemia 1, both enzymatic functions of AASS are defective and patients have increased serum lysine and possibly increased saccharopine. Some individuals, however, retain significant amounts of lysine-ketoglutarate reductase and present with saccharopinuria, a metabolic condition with few, if any, clinical manifestations.1 Publication
Disease descriptionAn autosomal recessive metabolic condition with variable clinical features. Some patients present with non-specific seizures, hypotonia, or mildly delayed psychomotor development, and increased serum lysine and pipecolic acid on laboratory analysis. However, about half of the probands are reported to be asymptomatic, and hyperlysinemia is generally considered to be a benign metabolic variant.
See also OMIM:238700
2,4-dienoyl-CoA reductase deficiency (DECRD)1 Publication
The protein represented in this entry is involved in disease pathogenesis. A selective decrease in mitochondrial NADP(H) levels due to NADK2 mutations causes a deficiency of NADPH-dependent mitochondrial enzymes, such as DECR1 and AASS.1 Publication
Disease descriptionA rare, autosomal recessive, inborn error of polyunsaturated fatty acids and lysine metabolism, resulting in mitochondrial dysfunction. Affected individuals have a severe encephalopathy with neurologic and metabolic abnormalities beginning in early infancy. Laboratory studies show increased C10:2 carnitine levels and hyperlysinemia.
See also OMIM:616034

Organism-specific databases

DisGeNETi10157
MalaCardsiAASS
MIMi238700 phenotype
616034 phenotype
OpenTargetsiENSG00000008311
Orphaneti2203 Hyperlysinemia
3124 Saccharopinuria
PharmGKBiPA24369

Chemistry databases

DrugBankiDB00142 L-Glutamic Acid
DB04207 N-(5-Amino-5-Carboxypentyl)Glutamic Acid
DB00157 NADH
DB02338 Nadph Dihydro-Nicotinamide-Adenine-Dinucleotidephosphate

Polymorphism and mutation databases

BioMutaiAASS
DMDMi46396032

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 32MitochondrionBy similarityAdd BLAST32
ChainiPRO_000000105233 – 926Alpha-aminoadipic semialdehyde synthase, mitochondrialAdd BLAST894

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei48N6-acetyllysineBy similarity1
Modified residuei56N6-acetyllysineBy similarity1
Modified residuei93N6-acetyllysine; alternateBy similarity1
Modified residuei93N6-succinyllysine; alternateBy similarity1
Modified residuei128N6-acetyllysineBy similarity1
Modified residuei138N6-acetyllysine; alternateBy similarity1
Modified residuei138N6-succinyllysine; alternateBy similarity1
Modified residuei274N6-succinyllysineBy similarity1
Modified residuei286N6-acetyllysine; alternateBy similarity1
Modified residuei286N6-succinyllysine; alternateBy similarity1
Modified residuei333N6-succinyllysineBy similarity1
Modified residuei458N6-acetyllysine; alternateBy similarity1
Modified residuei458N6-succinyllysine; alternateBy similarity1
Modified residuei523N6-acetyllysine; alternateBy similarity1
Modified residuei523N6-succinyllysine; alternateBy similarity1
Modified residuei535N6-acetyllysine; alternateBy similarity1
Modified residuei535N6-succinyllysine; alternateBy similarity1
Modified residuei584N6-acetyllysine; alternateBy similarity1
Modified residuei584N6-succinyllysine; alternateBy similarity1
Modified residuei707N6-acetyllysineBy similarity1
Modified residuei732N6-succinyllysineBy similarity1
Modified residuei739N6-acetyllysineBy similarity1
Modified residuei761N6-acetyllysine; alternateBy similarity1
Modified residuei761N6-succinyllysine; alternateBy similarity1
Modified residuei780N6-acetyllysineBy similarity1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiQ9UDR5
MaxQBiQ9UDR5
PaxDbiQ9UDR5
PeptideAtlasiQ9UDR5
PRIDEiQ9UDR5
ProteomicsDBi84114

PTM databases

CarbonylDBiQ9UDR5
iPTMnetiQ9UDR5
PhosphoSitePlusiQ9UDR5

Expressioni

Tissue specificityi

Expressed in all 16 tissues examined with highest expression in the liver.

Inductioni

Induced by starvation.By similarity

Gene expression databases

BgeeiENSG00000008311 Expressed in 200 organ(s), highest expression level in right ovary
CleanExiHS_AASS
ExpressionAtlasiQ9UDR5 baseline and differential
GenevisibleiQ9UDR5 HS

Organism-specific databases

HPAiHPA020637
HPA020728
HPA020734

Interactioni

Subunit structurei

Homodimer.By similarity

Protein-protein interaction databases

BioGridi115459, 12 interactors
IntActiQ9UDR5, 6 interactors
MINTiQ9UDR5
STRINGi9606.ENSP00000377040

Structurei

Secondary structure

1926
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9UDR5
SMRiQ9UDR5
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni33 – 455Lysine-ketoglutarate reductaseAdd BLAST423
Regioni477 – 926Saccharopine dehydrogenaseAdd BLAST450
Regioni577 – 578Saccharopine bindingBy similarity2
Regioni724 – 726Saccharopine bindingBy similarity3

Sequence similaritiesi

In the N-terminal section; belongs to the AlaDH/PNT family.Curated
In the C-terminal section; belongs to the saccharopine dehydrogenase family.Curated

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG0172 Eukaryota
COG1748 LUCA
GeneTreeiENSGT00390000013249
HOGENOMiHOG000252920
HOVERGENiHBG048688
InParanoidiQ9UDR5
KOiK14157
OMAiIHDKEYV
OrthoDBiEOG091G03D7
PhylomeDBiQ9UDR5
TreeFamiTF105728

Family and domain databases

InterProiView protein in InterPro
IPR007886 AlaDH/PNT_N
IPR007698 AlaDH/PNT_NAD(H)-bd
IPR036291 NAD(P)-bd_dom_sf
IPR032095 Sacchrp_dh_C
IPR005097 Sacchrp_dh_NADP
PfamiView protein in Pfam
PF05222 AlaDh_PNT_N, 1 hit
PF16653 Sacchrp_dh_C, 1 hit
PF03435 Sacchrp_dh_NADP, 1 hit
SMARTiView protein in SMART
SM01002 AlaDh_PNT_C, 1 hit
SM01003 AlaDh_PNT_N, 1 hit
SUPFAMiSSF51735 SSF51735, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All

Q9UDR5-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MLQVHRTGLG RLGVSLSKGL HHKAVLAVRR EDVNAWERRA PLAPKHIKGI
60 70 80 90 100
TNLGYKVLIQ PSNRRAIHDK DYVKAGGILQ EDISEACLIL GVKRPPEEKL
110 120 130 140 150
MSRKTYAFFS HTIKAQEANM GLLDEILKQE IRLIDYEKMV DHRGVRVVAF
160 170 180 190 200
GQWAGVAGMI NILHGMGLRL LALGHHTPFM HIGMAHNYRN SSQAVQAVRD
210 220 230 240 250
AGYEISLGLM PKSIGPLTFV FTGTGNVSKG AQAIFNELPC EYVEPHELKE
260 270 280 290 300
VSQTGDLRKV YGTVLSRHHH LVRKTDAVYD PAEYDKHPER YISRFNTDIA
310 320 330 340 350
PYTTCLINGI YWEQNTPRLL TRQDAQSLLA PGKFSPAGVE GCPALPHKLV
360 370 380 390 400
AICDISADTG GSIEFMTECT TIEHPFCMYD ADQHIIHDSV EGSGILMCSI
410 420 430 440 450
DNLPAQLPIE ATECFGDMLY PYVEEMILSD ATQPLESQNF SPVVRDAVIT
460 470 480 490 500
SNGTLPDKYK YIQTLRESRE RAQSLSMGTR RKVLVLGSGY ISEPVLEYLS
510 520 530 540 550
RDGNIEITVG SDMKNQIEQL GKKYNINPVS MDICKQEEKL GFLVAKQDLV
560 570 580 590 600
ISLLPYVLHP LVAKACITNK VNMVTASYIT PALKELEKSV EDAGITIIGE
610 620 630 640 650
LGLDPGLDHM LAMETIDKAK EVGATIESYI SYCGGLPAPE HSNNPLRYKF
660 670 680 690 700
SWSPVGVLMN VMQSATYLLD GKVVNVAGGI SFLDAVTSMD FFPGLNLEGY
710 720 730 740 750
PNRDSTKYAE IYGISSAHTL LRGTLRYKGY MKALNGFVKL GLINREALPA
760 770 780 790 800
FRPEANPLTW KQLLCDLVGI SPSSEHDVLK EAVLKKLGGD NTQLEAAEWL
810 820 830 840 850
GLLGDEQVPQ AESILDALSK HLVMKLSYGP EEKDMIVMRD SFGIRHPSGH
860 870 880 890 900
LEHKTIDLVA YGDINGFSAM AKTVGLPTAM AAKMLLDGEI GAKGLMGPFS
910 920
KEIYGPILER IKAEGIIYTT QSTIKP
Length:926
Mass (Da):102,132
Last modified:May 1, 2000 - v1
Checksum:iCB4194014351A18D
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F8WAH1F8WAH1_HUMAN
Alpha-aminoadipic semialdehyde synt...
AASS
732Annotation score:
F8WE53F8WE53_HUMAN
Alpha-aminoadipic semialdehyde synt...
AASS
511Annotation score:
H7C0C6H7C0C6_HUMAN
Alpha-aminoadipic semialdehyde synt...
AASS
21Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti589S → C in CAA07619 (Ref. 2) Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF229180 mRNA Translation: AAF44328.1
AJ007714 mRNA Translation: CAA07619.2
AC006020 Genomic DNA Translation: AAF03526.1
CCDSiCCDS5783.1
RefSeqiNP_005754.2, NM_005763.3
UniGeneiHs.156738

Genome annotation databases

EnsembliENST00000393376; ENSP00000377040; ENSG00000008311
ENST00000417368; ENSP00000403768; ENSG00000008311
GeneIDi10157
KEGGihsa:10157
UCSCiuc003vka.4 human

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF229180 mRNA Translation: AAF44328.1
AJ007714 mRNA Translation: CAA07619.2
AC006020 Genomic DNA Translation: AAF03526.1
CCDSiCCDS5783.1
RefSeqiNP_005754.2, NM_005763.3
UniGeneiHs.156738

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5L76X-ray2.57A455-926[»]
5L78X-ray2.68A/B455-926[»]
5O1NX-ray2.28A455-926[»]
5O1OX-ray2.48A/B455-926[»]
5O1PX-ray1.90A455-926[»]
ProteinModelPortaliQ9UDR5
SMRiQ9UDR5
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115459, 12 interactors
IntActiQ9UDR5, 6 interactors
MINTiQ9UDR5
STRINGi9606.ENSP00000377040

Chemistry databases

DrugBankiDB00142 L-Glutamic Acid
DB04207 N-(5-Amino-5-Carboxypentyl)Glutamic Acid
DB00157 NADH
DB02338 Nadph Dihydro-Nicotinamide-Adenine-Dinucleotidephosphate

PTM databases

CarbonylDBiQ9UDR5
iPTMnetiQ9UDR5
PhosphoSitePlusiQ9UDR5

Polymorphism and mutation databases

BioMutaiAASS
DMDMi46396032

Proteomic databases

EPDiQ9UDR5
MaxQBiQ9UDR5
PaxDbiQ9UDR5
PeptideAtlasiQ9UDR5
PRIDEiQ9UDR5
ProteomicsDBi84114

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000393376; ENSP00000377040; ENSG00000008311
ENST00000417368; ENSP00000403768; ENSG00000008311
GeneIDi10157
KEGGihsa:10157
UCSCiuc003vka.4 human

Organism-specific databases

CTDi10157
DisGeNETi10157
EuPathDBiHostDB:ENSG00000008311.14
GeneCardsiAASS
HGNCiHGNC:17366 AASS
HPAiHPA020637
HPA020728
HPA020734
MalaCardsiAASS
MIMi238700 phenotype
605113 gene
616034 phenotype
neXtProtiNX_Q9UDR5
OpenTargetsiENSG00000008311
Orphaneti2203 Hyperlysinemia
3124 Saccharopinuria
PharmGKBiPA24369
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0172 Eukaryota
COG1748 LUCA
GeneTreeiENSGT00390000013249
HOGENOMiHOG000252920
HOVERGENiHBG048688
InParanoidiQ9UDR5
KOiK14157
OMAiIHDKEYV
OrthoDBiEOG091G03D7
PhylomeDBiQ9UDR5
TreeFamiTF105728

Enzyme and pathway databases

UniPathwayi
UPA00868;UER00835

UPA00868;UER00836

BioCyciMetaCyc:HS00244-MONOMER
ReactomeiR-HSA-71064 Lysine catabolism
SABIO-RKiQ9UDR5

Miscellaneous databases

ChiTaRSiAASS human
GeneWikiiAASS
GenomeRNAii10157
PROiPR:Q9UDR5
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000008311 Expressed in 200 organ(s), highest expression level in right ovary
CleanExiHS_AASS
ExpressionAtlasiQ9UDR5 baseline and differential
GenevisibleiQ9UDR5 HS

Family and domain databases

InterProiView protein in InterPro
IPR007886 AlaDH/PNT_N
IPR007698 AlaDH/PNT_NAD(H)-bd
IPR036291 NAD(P)-bd_dom_sf
IPR032095 Sacchrp_dh_C
IPR005097 Sacchrp_dh_NADP
PfamiView protein in Pfam
PF05222 AlaDh_PNT_N, 1 hit
PF16653 Sacchrp_dh_C, 1 hit
PF03435 Sacchrp_dh_NADP, 1 hit
SMARTiView protein in SMART
SM01002 AlaDh_PNT_C, 1 hit
SM01003 AlaDh_PNT_N, 1 hit
SUPFAMiSSF51735 SSF51735, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiAASS_HUMAN
AccessioniPrimary (citable) accession number: Q9UDR5
Secondary accession number(s): O95462
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 13, 2004
Last sequence update: May 1, 2000
Last modified: September 12, 2018
This is version 152 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
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