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Protein

Alpha-aminoadipic semialdehyde synthase, mitochondrial

Gene

AASS

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

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

Pathwayi

GO - Molecular functioni

  1. saccharopine dehydrogenase (NAD+, L-glutamate-forming) activity Source: UniProtKB
  2. saccharopine dehydrogenase (NADP+, L-lysine-forming) activity Source: Reactome

GO - Biological processi

  1. cellular nitrogen compound metabolic process Source: Reactome
  2. L-lysine catabolic process to acetyl-CoA via saccharopine Source: UniProtKB-UniPathway
  3. lysine catabolic process Source: UniProtKB
  4. protein tetramerization Source: UniProtKB
  5. small molecule metabolic process Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Ligandi

NAD, NADP

Enzyme and pathway databases

BioCyciMetaCyc:HS00244-MONOMER.
ReactomeiREACT_1298. Lysine catabolism.
SABIO-RKQ9UDR5.
UniPathwayiUPA00868; 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
ProteomesiUP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:17366. AASS.

Subcellular locationi

  1. Mitochondrion By similarity

GO - Cellular componenti

  1. intracellular membrane-bounded organelle Source: HPA
  2. mitochondrial matrix Source: Reactome
  3. mitochondrion Source: UniProtKB
Complete GO annotation...

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.

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.

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

MIMi238700. phenotype.
616034. phenotype.
Orphaneti2203. Hyperlysinemia.
3124. Saccharopinuria.
PharmGKBiPA24369.

Polymorphism and mutation databases

BioMutaiAASS.
DMDMi46396032.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transit peptidei1 – 3232MitochondrionBy similarityAdd
BLAST
Chaini33 – 926894Alpha-aminoadipic semialdehyde synthase, mitochondrialPRO_0000001052Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei48 – 481N6-acetyllysineBy similarity
Modified residuei56 – 561N6-acetyllysineBy similarity
Modified residuei93 – 931N6-acetyllysine; alternateBy similarity
Modified residuei93 – 931N6-succinyllysine; alternateBy similarity
Modified residuei128 – 1281N6-acetyllysineBy similarity
Modified residuei138 – 1381N6-acetyllysine; alternateBy similarity
Modified residuei138 – 1381N6-succinyllysine; alternateBy similarity
Modified residuei274 – 2741N6-succinyllysineBy similarity
Modified residuei286 – 2861N6-acetyllysine; alternateBy similarity
Modified residuei286 – 2861N6-succinyllysine; alternateBy similarity
Modified residuei333 – 3331N6-succinyllysineBy similarity
Modified residuei458 – 4581N6-acetyllysine; alternateBy similarity
Modified residuei458 – 4581N6-succinyllysine; alternateBy similarity
Modified residuei523 – 5231N6-acetyllysine; alternateBy similarity
Modified residuei523 – 5231N6-succinyllysine; alternateBy similarity
Modified residuei535 – 5351N6-acetyllysine; alternateBy similarity
Modified residuei535 – 5351N6-succinyllysine; alternateBy similarity
Modified residuei584 – 5841N6-acetyllysine; alternateBy similarity
Modified residuei584 – 5841N6-succinyllysine; alternateBy similarity
Modified residuei707 – 7071N6-acetyllysineBy similarity
Modified residuei732 – 7321N6-succinyllysineBy similarity
Modified residuei739 – 7391N6-acetyllysineBy similarity
Modified residuei761 – 7611N6-acetyllysine; alternateBy similarity
Modified residuei761 – 7611N6-succinyllysine; alternateBy similarity
Modified residuei780 – 7801N6-acetyllysineBy similarity

Keywords - PTMi

Acetylation

Proteomic databases

MaxQBiQ9UDR5.
PaxDbiQ9UDR5.
PeptideAtlasiQ9UDR5.
PRIDEiQ9UDR5.

PTM databases

PhosphoSiteiQ9UDR5.

Expressioni

Tissue specificityi

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

Inductioni

Induced by starvation.By similarity

Gene expression databases

BgeeiQ9UDR5.
CleanExiHS_AASS.
ExpressionAtlasiQ9UDR5. baseline and differential.
GenevestigatoriQ9UDR5.

Organism-specific databases

HPAiHPA020637.
HPA020728.
HPA020734.

Interactioni

Subunit structurei

Homodimer.By similarity

Protein-protein interaction databases

BioGridi115459. 6 interactions.
IntActiQ9UDR5. 2 interactions.
MINTiMINT-2820994.
STRINGi9606.ENSP00000377040.

Structurei

3D structure databases

ProteinModelPortaliQ9UDR5.
SMRiQ9UDR5. Positions 30-424, 481-924.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni33 – 455423Lysine-ketoglutarate reductaseAdd
BLAST
Regioni477 – 926450Saccharopine dehydrogenaseAdd
BLAST

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

eggNOGiCOG1748.
GeneTreeiENSGT00390000013249.
HOGENOMiHOG000252920.
HOVERGENiHBG048688.
InParanoidiQ9UDR5.
KOiK14157.
OMAiEIYGISS.
OrthoDBiEOG7F7W7Z.
PhylomeDBiQ9UDR5.
TreeFamiTF105728.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
InterProiIPR007886. AlaDH/PNT_N.
IPR007698. AlaDH/PNT_NAD(H)-bd.
IPR016040. NAD(P)-bd_dom.
IPR005097. Saccharopine_DH/HSpermid_syn.
[Graphical view]
PfamiPF01262. AlaDh_PNT_C. 1 hit.
PF05222. AlaDh_PNT_N. 1 hit.
PF03435. Saccharop_dh. 1 hit.
[Graphical view]
SMARTiSM01002. AlaDh_PNT_C. 1 hit.
SM01003. AlaDh_PNT_N. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

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

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti589 – 5891S → C in CAA07619 (Ref. 2) Curated

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.3. human.

Polymorphism and mutation databases

BioMutaiAASS.

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

ProteinModelPortaliQ9UDR5.
SMRiQ9UDR5. Positions 30-424, 481-924.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115459. 6 interactions.
IntActiQ9UDR5. 2 interactions.
MINTiMINT-2820994.
STRINGi9606.ENSP00000377040.

PTM databases

PhosphoSiteiQ9UDR5.

Polymorphism and mutation databases

BioMutaiAASS.
DMDMi46396032.

Proteomic databases

MaxQBiQ9UDR5.
PaxDbiQ9UDR5.
PeptideAtlasiQ9UDR5.
PRIDEiQ9UDR5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000393376; ENSP00000377040; ENSG00000008311.
ENST00000417368; ENSP00000403768; ENSG00000008311.
GeneIDi10157.
KEGGihsa:10157.
UCSCiuc003vka.3. human.

Organism-specific databases

CTDi10157.
GeneCardsiGC07M121713.
HGNCiHGNC:17366. AASS.
HPAiHPA020637.
HPA020728.
HPA020734.
MIMi238700. phenotype.
605113. gene.
616034. phenotype.
neXtProtiNX_Q9UDR5.
Orphaneti2203. Hyperlysinemia.
3124. Saccharopinuria.
PharmGKBiPA24369.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG1748.
GeneTreeiENSGT00390000013249.
HOGENOMiHOG000252920.
HOVERGENiHBG048688.
InParanoidiQ9UDR5.
KOiK14157.
OMAiEIYGISS.
OrthoDBiEOG7F7W7Z.
PhylomeDBiQ9UDR5.
TreeFamiTF105728.

Enzyme and pathway databases

UniPathwayiUPA00868; UER00835.
UPA00868; UER00836.
BioCyciMetaCyc:HS00244-MONOMER.
ReactomeiREACT_1298. Lysine catabolism.
SABIO-RKQ9UDR5.

Miscellaneous databases

ChiTaRSiAASS. human.
GeneWikiiAASS.
GenomeRNAii10157.
NextBioi38452.
PROiQ9UDR5.
SOURCEiSearch...

Gene expression databases

BgeeiQ9UDR5.
CleanExiHS_AASS.
ExpressionAtlasiQ9UDR5. baseline and differential.
GenevestigatoriQ9UDR5.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
InterProiIPR007886. AlaDH/PNT_N.
IPR007698. AlaDH/PNT_NAD(H)-bd.
IPR016040. NAD(P)-bd_dom.
IPR005097. Saccharopine_DH/HSpermid_syn.
[Graphical view]
PfamiPF01262. AlaDh_PNT_C. 1 hit.
PF05222. AlaDh_PNT_N. 1 hit.
PF03435. Saccharop_dh. 1 hit.
[Graphical view]
SMARTiSM01002. AlaDh_PNT_C. 1 hit.
SM01003. AlaDh_PNT_N. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Identification of the alpha-aminoadipic semialdehyde synthase gene, which is defective in familial hyperlysinemia."
    Sacksteder K.A., Biery B.J., Morrell J.C., Goodman B.K., Geisbrecht B.V., Cox R.P., Gould S.J., Geraghty M.T.
    Am. J. Hum. Genet. 66:1736-1743(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION, INVOLVEMENT IN HYPLYS1.
  2. "Cloning and expression analysis of the LKR/SDH gene in human tissues."
    Papes F., Kemper E.L., Cord-Neto G., Langone F., Arruda P.
    Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Liver.
  3. "The DNA sequence of human chromosome 7."
    Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L.
    , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
    Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  5. "Mitochondrial NADP(H) deficiency due to a mutation in NADK2 causes dienoyl-CoA reductase deficiency with hyperlysinemia."
    Houten S.M., Denis S., Te Brinke H., Jongejan A., van Kampen A.H., Bradley E.J., Baas F., Hennekam R.C., Millington D.S., Young S.P., Frazier D.M., Gucsavas-Calikoglu M., Wanders R.J.
    Hum. Mol. Genet. 23:5009-5016(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN DECRD.
  6. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.

Entry informationi

Entry nameiAASS_HUMAN
AccessioniPrimary (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: April 29, 2015
This is version 122 of the entry and version 1 of the sequence. [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

Complete proteome, Multifunctional enzyme, Reference proteome

Documents

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

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.