UniProtKB - Q9UDR5 (AASS_HUMAN)
Protein
Alpha-aminoadipic semialdehyde synthase, mitochondrial
Gene
AASS
Organism
Homo sapiens (Human)
Status
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
: L-lysine degradation via saccharopine pathway Pathwayi
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:
- Lysine ketoglutarate reductase (AASS), Alpha-aminoadipic semialdehyde synthase, mitochondrial (AASS), Lysine ketoglutarate reductase (AASS)
- Lysine ketoglutarate reductase (AASS), Alpha-aminoadipic semialdehyde synthase, mitochondrial (AASS), Lysine ketoglutarate reductase (AASS)
- no protein annotated in this organism
- Kynurenine/alpha-aminoadipate aminotransferase, mitochondrial (AADAT)
- no protein annotated in this organism
- Dihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex, mitochondrial (DLST), Dihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex, mitochondrial (DLST), Dihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex, mitochondrial (DLST), Dihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex, mitochondrial (E2k)
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 604 | SaccharopineBy similarity | 1 | |
Binding sitei | 653 | NADP; via amide nitrogenBy similarity | 1 | |
Binding sitei | 703 | SaccharopineBy similarity | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 488 – 491 | NADPBy similarity | 4 | |
Nucleotide bindingi | 603 – 605 | NADPBy similarity | 3 |
GO - Molecular functioni
- histone binding Source: FlyBase
- saccharopine dehydrogenase (NAD+, L-glutamate-forming) activity Source: UniProtKB
- saccharopine dehydrogenase (NAD+, L-lysine-forming) activity Source: FlyBase
- saccharopine dehydrogenase (NADP+, L-lysine-forming) activity Source: UniProtKB-EC
- saccharopine dehydrogenase activity Source: GO_Central
- transcription corepressor activity Source: FlyBase
GO - Biological processi
- L-lysine catabolic process to acetyl-CoA via saccharopine Source: UniProtKB-UniPathway
- lysine biosynthetic process via aminoadipic acid Source: GO_Central
- lysine catabolic process Source: Reactome
- negative regulation of histone methylation Source: FlyBase
- negative regulation of transcription by RNA polymerase II Source: FlyBase
Keywordsi
Molecular function | Multifunctional enzyme, Oxidoreductase |
Ligand | NAD, NADP |
Enzyme and pathway databases
BioCyci | MetaCyc:HS00244-MONOMER |
PathwayCommonsi | Q9UDR5 |
Reactomei | R-HSA-71064, Lysine catabolism |
SABIO-RKi | Q9UDR5 |
UniPathwayi | UPA00868;UER00835 UPA00868;UER00836 |
Names & Taxonomyi
Protein namesi | |
Gene namesi | Name:AASS |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:17366, AASS |
MIMi | 605113, gene |
neXtProti | NX_Q9UDR5 |
VEuPathDBi | HostDB:ENSG00000008311.14 |
Subcellular locationi
Mitochondrion
- Mitochondrion By similarity
Cytosol
- cytosol Source: FlyBase
Mitochondrion
- mitochondrial matrix Source: Reactome
- mitochondrion Source: HPA
Nucleus
- nucleus Source: FlyBase
Other locations
- cytoplasm Source: GO_Central
- intracellular membrane-bounded organelle Source: HPA
Keywords - Cellular componenti
MitochondrionPathology & Biotechi
Involvement in diseasei
Hyperlysinemia, 1 (HYPLYS1)1 Publication
The disease is caused by variants 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.
Related information in OMIM2,4-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.
Related information in OMIMOrganism-specific databases
DisGeNETi | 10157 |
MalaCardsi | AASS |
MIMi | 238700, phenotype 616034, phenotype |
OpenTargetsi | ENSG00000008311 |
Orphaneti | 2203, Hyperlysinemia 3124, Saccharopinuria |
PharmGKBi | PA24369 |
Miscellaneous databases
Pharosi | Q9UDR5, Tbio |
Chemistry databases
DrugBanki | DB00142, Glutamic acid DB04207, L-Saccharopine DB00157, NADH DB02338, NADPH |
Genetic variation databases
BioMutai | AASS |
DMDMi | 46396032 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transit peptidei | 1 – 32 | MitochondrionBy similarityAdd BLAST | 32 | |
ChainiPRO_0000001052 | 33 – 926 | Alpha-aminoadipic semialdehyde synthase, mitochondrialAdd BLAST | 894 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 48 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 56 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 93 | N6-acetyllysine; alternateBy similarity | 1 | |
Modified residuei | 93 | N6-succinyllysine; alternateBy similarity | 1 | |
Modified residuei | 128 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 138 | N6-acetyllysine; alternateBy similarity | 1 | |
Modified residuei | 138 | N6-succinyllysine; alternateBy similarity | 1 | |
Modified residuei | 274 | N6-succinyllysineBy similarity | 1 | |
Modified residuei | 286 | N6-acetyllysine; alternateBy similarity | 1 | |
Modified residuei | 286 | N6-succinyllysine; alternateBy similarity | 1 | |
Modified residuei | 333 | N6-succinyllysineBy similarity | 1 | |
Modified residuei | 458 | N6-acetyllysine; alternateBy similarity | 1 | |
Modified residuei | 458 | N6-succinyllysine; alternateBy similarity | 1 | |
Modified residuei | 523 | N6-acetyllysine; alternateBy similarity | 1 | |
Modified residuei | 523 | N6-succinyllysine; alternateBy similarity | 1 | |
Modified residuei | 535 | N6-acetyllysine; alternateBy similarity | 1 | |
Modified residuei | 535 | N6-succinyllysine; alternateBy similarity | 1 | |
Modified residuei | 584 | N6-acetyllysine; alternateBy similarity | 1 | |
Modified residuei | 584 | N6-succinyllysine; alternateBy similarity | 1 | |
Modified residuei | 707 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 732 | N6-succinyllysineBy similarity | 1 | |
Modified residuei | 739 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 761 | N6-acetyllysine; alternateBy similarity | 1 | |
Modified residuei | 761 | N6-succinyllysine; alternateBy similarity | 1 | |
Modified residuei | 780 | N6-acetyllysineBy similarity | 1 |
Keywords - PTMi
AcetylationProteomic databases
EPDi | Q9UDR5 |
jPOSTi | Q9UDR5 |
MassIVEi | Q9UDR5 |
MaxQBi | Q9UDR5 |
PaxDbi | Q9UDR5 |
PeptideAtlasi | Q9UDR5 |
PRIDEi | Q9UDR5 |
ProteomicsDBi | 84114 |
PTM databases
CarbonylDBi | Q9UDR5 |
iPTMneti | Q9UDR5 |
MetOSitei | Q9UDR5 |
PhosphoSitePlusi | Q9UDR5 |
Expressioni
Tissue specificityi
Expressed in all 16 tissues examined with highest expression in the liver.
Inductioni
Induced by starvation.By similarity
Gene expression databases
Bgeei | ENSG00000008311, Expressed in right ovary and 212 other tissues |
ExpressionAtlasi | Q9UDR5, baseline and differential |
Genevisiblei | Q9UDR5, HS |
Organism-specific databases
HPAi | ENSG00000008311, Low tissue specificity |
Interactioni
Subunit structurei
Homodimer.
By similarityGO - Molecular functioni
- histone binding Source: FlyBase
Protein-protein interaction databases
BioGRIDi | 115459, 36 interactors |
IntActi | Q9UDR5, 9 interactors |
MINTi | Q9UDR5 |
STRINGi | 9606.ENSP00000377040 |
Miscellaneous databases
RNActi | Q9UDR5, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q9UDR5 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 33 – 455 | Lysine-ketoglutarate reductaseAdd BLAST | 423 | |
Regioni | 477 – 926 | Saccharopine dehydrogenaseAdd BLAST | 450 | |
Regioni | 577 – 578 | Saccharopine bindingBy similarity | 2 | |
Regioni | 724 – 726 | Saccharopine bindingBy similarity | 3 |
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 peptidePhylogenomic databases
eggNOGi | KOG0172, Eukaryota |
GeneTreei | ENSGT00390000013249 |
HOGENOMi | CLU_005231_0_1_1 |
InParanoidi | Q9UDR5 |
OMAi | KMEGRSE |
OrthoDBi | 498994at2759 |
PhylomeDBi | Q9UDR5 |
TreeFami | TF105728 |
Family and domain databases
InterProi | View 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 |
Pfami | View protein in Pfam PF05222, AlaDh_PNT_N, 1 hit PF16653, Sacchrp_dh_C, 1 hit PF03435, Sacchrp_dh_NADP, 1 hit |
SMARTi | View protein in SMART SM01002, AlaDh_PNT_C, 1 hit SM01003, AlaDh_PNT_N, 1 hit |
SUPFAMi | SSF51735, SSF51735, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All
Q9UDR5-1 [UniParc]FASTAAdd to basket
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
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketF8WAH1 | F8WAH1_HUMAN | Lysine ketoglutarate reductase | AASS | 732 | Annotation score: | ||
F8WE53 | F8WE53_HUMAN | Alpha-aminoadipic semialdehyde synt... | AASS | 511 | Annotation score: | ||
H7C0C6 | H7C0C6_HUMAN | Alpha-aminoadipic semialdehyde synt... | AASS | 21 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 589 | S → C in CAA07619 (Ref. 2) Curated | 1 |
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 |
CCDSi | CCDS5783.1 |
RefSeqi | NP_005754.2, NM_005763.3 |
Genome annotation databases
Ensembli | ENST00000393376; ENSP00000377040; ENSG00000008311 ENST00000417368; ENSP00000403768; ENSG00000008311 |
GeneIDi | 10157 |
KEGGi | hsa:10157 |
UCSCi | uc003vka.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 |
CCDSi | CCDS5783.1 |
RefSeqi | NP_005754.2, NM_005763.3 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
5L76 | X-ray | 2.57 | A | 455-926 | [»] | |
5L78 | X-ray | 2.68 | A/B | 455-926 | [»] | |
5O1N | X-ray | 2.28 | A | 455-926 | [»] | |
5O1O | X-ray | 2.48 | A/B | 455-926 | [»] | |
5O1P | X-ray | 1.90 | A | 455-926 | [»] | |
SMRi | Q9UDR5 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 115459, 36 interactors |
IntActi | Q9UDR5, 9 interactors |
MINTi | Q9UDR5 |
STRINGi | 9606.ENSP00000377040 |
Chemistry databases
DrugBanki | DB00142, Glutamic acid DB04207, L-Saccharopine DB00157, NADH DB02338, NADPH |
PTM databases
CarbonylDBi | Q9UDR5 |
iPTMneti | Q9UDR5 |
MetOSitei | Q9UDR5 |
PhosphoSitePlusi | Q9UDR5 |
Genetic variation databases
BioMutai | AASS |
DMDMi | 46396032 |
Proteomic databases
EPDi | Q9UDR5 |
jPOSTi | Q9UDR5 |
MassIVEi | Q9UDR5 |
MaxQBi | Q9UDR5 |
PaxDbi | Q9UDR5 |
PeptideAtlasi | Q9UDR5 |
PRIDEi | Q9UDR5 |
ProteomicsDBi | 84114 |
Protocols and materials databases
Antibodypediai | 17598, 193 antibodies |
Genome annotation databases
Ensembli | ENST00000393376; ENSP00000377040; ENSG00000008311 ENST00000417368; ENSP00000403768; ENSG00000008311 |
GeneIDi | 10157 |
KEGGi | hsa:10157 |
UCSCi | uc003vka.4, human |
Organism-specific databases
CTDi | 10157 |
DisGeNETi | 10157 |
GeneCardsi | AASS |
HGNCi | HGNC:17366, AASS |
HPAi | ENSG00000008311, Low tissue specificity |
MalaCardsi | AASS |
MIMi | 238700, phenotype 605113, gene 616034, phenotype |
neXtProti | NX_Q9UDR5 |
OpenTargetsi | ENSG00000008311 |
Orphaneti | 2203, Hyperlysinemia 3124, Saccharopinuria |
PharmGKBi | PA24369 |
VEuPathDBi | HostDB:ENSG00000008311.14 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0172, Eukaryota |
GeneTreei | ENSGT00390000013249 |
HOGENOMi | CLU_005231_0_1_1 |
InParanoidi | Q9UDR5 |
OMAi | KMEGRSE |
OrthoDBi | 498994at2759 |
PhylomeDBi | Q9UDR5 |
TreeFami | TF105728 |
Enzyme and pathway databases
UniPathwayi | UPA00868;UER00835 UPA00868;UER00836 |
BioCyci | MetaCyc:HS00244-MONOMER |
PathwayCommonsi | Q9UDR5 |
Reactomei | R-HSA-71064, Lysine catabolism |
SABIO-RKi | Q9UDR5 |
Miscellaneous databases
BioGRID-ORCSi | 10157, 9 hits in 872 CRISPR screens |
ChiTaRSi | AASS, human |
GeneWikii | AASS |
GenomeRNAii | 10157 |
Pharosi | Q9UDR5, Tbio |
PROi | PR:Q9UDR5 |
RNActi | Q9UDR5, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000008311, Expressed in right ovary and 212 other tissues |
ExpressionAtlasi | Q9UDR5, baseline and differential |
Genevisiblei | Q9UDR5, HS |
Family and domain databases
InterProi | View 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 |
Pfami | View protein in Pfam PF05222, AlaDh_PNT_N, 1 hit PF16653, Sacchrp_dh_C, 1 hit PF03435, Sacchrp_dh_NADP, 1 hit |
SMARTi | View protein in SMART SM01002, AlaDh_PNT_C, 1 hit SM01003, AlaDh_PNT_N, 1 hit |
SUPFAMi | SSF51735, SSF51735, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | AASS_HUMAN | |
Accessioni | Q9UDR5Primary (citable) accession number: Q9UDR5 Secondary accession number(s): O95462 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 13, 2004 |
Last sequence update: | May 1, 2000 | |
Last modified: | February 10, 2021 | |
This is version 167 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Reference proteomeDocuments
- Human chromosome 7
Human chromosome 7: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families