AASS

Protein identityUniProt · HPA

UniProt accession

Q9UDR5

Gene

AASS

Ensembl

ENSG00000008311

Chromosome

7

Canonical length

926 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Nucleoplasm,Vesicles,Mitochondria

Quaternary structure

Homotetramer

OverviewNCBI Gene

This gene encodes a bifunctional enzyme that catalyzes the first two steps in the mammalian lysine degradation pathway. The N-terminal and the C-terminal portions of this enzyme contain lysine-ketoglutarate reductase and saccharopine dehydrogenase activity, respectively, resulting in the conversion of lysine to alpha-aminoadipic semialdehyde. Mutations in this gene are associated with familial hyperlysinemia. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

926 residues, UniProt reviewed canonical sequence.

>Q9UDR5|AASS
     1  MLQVHRTGLG RLGVSLSKGL HHKAVLAVRR EDVNAWERRA PLAPKHIKGI TNLGYKVLIQ
    61  PSNRRAIHDK DYVKAGGILQ EDISEACLIL GVKRPPEEKL MSRKTYAFFS HTIKAQEANM
   121  GLLDEILKQE IRLIDYEKMV DHRGVRVVAF GQWAGVAGMI NILHGMGLRL LALGHHTPFM
   181  HIGMAHNYRN SSQAVQAVRD AGYEISLGLM PKSIGPLTFV FTGTGNVSKG AQAIFNELPC
   241  EYVEPHELKE VSQTGDLRKV YGTVLSRHHH LVRKTDAVYD PAEYDKHPER YISRFNTDIA
   301  PYTTCLINGI YWEQNTPRLL TRQDAQSLLA PGKFSPAGVE GCPALPHKLV AICDISADTG
   361  GSIEFMTECT TIEHPFCMYD ADQHIIHDSV EGSGILMCSI DNLPAQLPIE ATECFGDMLY
   421  PYVEEMILSD ATQPLESQNF SPVVRDAVIT SNGTLPDKYK YIQTLRESRE RAQSLSMGTR
   481  RKVLVLGSGY ISEPVLEYLS RDGNIEITVG SDMKNQIEQL GKKYNINPVS MDICKQEEKL
   541  GFLVAKQDLV ISLLPYVLHP LVAKACITNK VNMVTASYIT PALKELEKSV EDAGITIIGE
   601  LGLDPGLDHM LAMETIDKAK EVGATIESYI SYCGGLPAPE HSNNPLRYKF SWSPVGVLMN
   661  VMQSATYLLD GKVVNVAGGI SFLDAVTSMD FFPGLNLEGY PNRDSTKYAE IYGISSAHTL
   721  LRGTLRYKGY MKALNGFVKL GLINREALPA FRPEANPLTW KQLLCDLVGI SPSSEHDVLK
   781  EAVLKKLGGD NTQLEAAEWL GLLGDEQVPQ AESILDALSK HLVMKLSYGP EEKDMIVMRD
   841  SFGIRHPSGH LEHKTIDLVA YGDINGFSAM AKTVGLPTAM AAKMLLDGEI GAKGLMGPFS
   901  KEIYGPILER IKAEGIIYTT QSTIKP

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against AASS can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.24

Highest tissue expression

47 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about AASS.

Disease | AllUniProt

Conditions AASS is implicated in, by any mechanism.

• Hyperlysinemia, 1 (HYPLYS1) MIM:238700
• 2,4-dienoyl-CoA reductase deficiency (DECRD) MIM:616034

Disease | GeneticClinVar

23 pathogenic / likely-pathogenic of 315 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Hyperlysinemia
• HYPERLYSINEMIA, TYPE I

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.81

gnomAD pLI

0

gnomAD missense Z

0.88

DepMap mean gene effect

0.02

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• L-lysine catabolic process to acetyl-CoA via saccharopine
• lysine biosynthetic process via aminoadipic acid
• lysine catabolic process
• negative regulation of transcription by RNA polymerase II

Molecular functions

• histone binding
• transcription corepressor activity
• saccharopine dehydrogenase (NAD+, L-glutamate-forming) activity
• saccharopine dehydrogenase (NAD+, L-lysine-forming) activity
• saccharopine dehydrogenase (NADP+, L-lysine-forming) activity
• saccharopine dehydrogenase activity

Cellular components

• cytoplasm
• cytosol
• mitochondrial matrix
• mitochondrion
• nucleus

Protein domainsUniProt · Pfam · InterPro

• Saccharopine dehydrogenase, NADP binding domain
• Alanine dehydrogenase/pyridine nucleotide transhydrogenase, NAD(H)-binding domain
• Alanine dehydrogenase/pyridine nucleotide transhydrogenase, N-terminal
• NAD(P)-binding domain superfamily
• Saccharopine dehydrogenase NADP binding domain
• Alanine dehydrogenase/PNT, N-terminal domain
• Saccharopine dehydrogenase-like, C-terminal
• Alpha-aminoadipic semialdehyde synthase
• Saccharopine dehydrogenase C-terminal domain

KeywordsUniProt

• Acetylation
• Mitochondrion
• Multifunctional enzyme
• NAD
• NADP
• Oxidoreductase
• Transit peptide