Reviewed, UniProtKB/Swiss-Prot Q9UDR5 (AASS_HUMAN)

Names and origin

Protein names

Recommended name:
    Alpha-aminoadipic semialdehyde synthase, mitochondrial
Alternative name(s):
    LKR/SDH
Including the following 2 domains:
    1- Recommended name:
            Lysine ketoglutarate reductase
                Short name=LKR
                Short name=LOR
              EC=1.5.1.8
    2- Recommended name:
            Saccharopine dehydrogenase
                Short name=SDH
              EC=1.5.1.9

Gene names

Name:

AASS

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	926 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	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 activity	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 + 2-aminoadipate 6-semialdehyde + NADH.
Pathway	Amino-acid degradation; L-lysine degradation via saccharopine pathway; glutaryl-CoA from L-lysine: step 1/6. Amino-acid degradation; L-lysine degradation via saccharopine pathway; glutaryl-CoA from L-lysine: step 2/6.
Subunit structure	Homodimer By similarity.
Subcellular location	Mitochondrion By similarity.
Tissue specificity	Expressed in all 16 tissues examined with highest expression in the liver.
Induction	Induced by starvation By similarity.
Involvement in disease	Defects in AASS are the cause of hyperlysinemia [MIM:238700]. Hyperlysinemia is an autosomal recessive condition characterized by hyperlysinemia lysinuria and variable saccharopinuria.
Sequence similarities	In the N-terminal section; belongs to the AlaDH/PNT family. In the C-terminal section; belongs to the saccharopine dehydrogenase family.

Ontologies

Keywords
Cellular component	Mitochondrion
Domain	Transit peptide
Ligand	NAD NADP
Molecular function	Oxidoreductase
Technical term	Multifunctional enzyme
Gene Ontology (GO)
Biological process	oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW protein tetramerization Traceable author statement. Source: UniProtKB
Cellular component	mitochondrion Traceable author statement. Source: UniProtKB
Molecular function	binding Inferred from electronic annotation. Source: InterPro electron carrier activity Inferred from electronic annotation. Source: InterPro saccharopine dehydrogenase (NAD+, L-glutamate-forming) activity Ref.1 Non-traceable author statement. Source: UniProtKB saccharopine dehydrogenase (NADP+, L-lysine-forming) activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 32	32	Mitochondrion By similarity
	Chain	33 – 926	894	Alpha-aminoadipic semialdehyde synthase, mitochondrial		PRO_0000001052
Regions
	Region	33 – 455	423	Lysine-ketoglutarate reductase
	Region	477 – 926	450	Saccharopine dehydrogenase
Experimental info
	Sequence conflict	589	1	S → C in CAA07619. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q9UDR5-1 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: CB4194014351A18D	FASTA	926	102,132
	10 20 30 40 50 60 MLQVHRTGLG RLGVSLSKGL HHKAVLAVRR EDVNAWERRA PLAPKHIKGI TNLGYKVLIQ 70 80 90 100 110 120 PSNRRAIHDK DYVKAGGILQ EDISEACLIL GVKRPPEEKL MSRKTYAFFS HTIKAQEANM 130 140 150 160 170 180 GLLDEILKQE IRLIDYEKMV DHRGVRVVAF GQWAGVAGMI NILHGMGLRL LALGHHTPFM 190 200 210 220 230 240 HIGMAHNYRN SSQAVQAVRD AGYEISLGLM PKSIGPLTFV FTGTGNVSKG AQAIFNELPC 250 260 270 280 290 300 EYVEPHELKE VSQTGDLRKV YGTVLSRHHH LVRKTDAVYD PAEYDKHPER YISRFNTDIA 310 320 330 340 350 360 PYTTCLINGI YWEQNTPRLL TRQDAQSLLA PGKFSPAGVE GCPALPHKLV AICDISADTG 370 380 390 400 410 420 GSIEFMTECT TIEHPFCMYD ADQHIIHDSV EGSGILMCSI DNLPAQLPIE ATECFGDMLY 430 440 450 460 470 480 PYVEEMILSD ATQPLESQNF SPVVRDAVIT SNGTLPDKYK YIQTLRESRE RAQSLSMGTR 490 500 510 520 530 540 RKVLVLGSGY ISEPVLEYLS RDGNIEITVG SDMKNQIEQL GKKYNINPVS MDICKQEEKL 550 560 570 580 590 600 GFLVAKQDLV ISLLPYVLHP LVAKACITNK VNMVTASYIT PALKELEKSV EDAGITIIGE 610 620 630 640 650 660 LGLDPGLDHM LAMETIDKAK EVGATIESYI SYCGGLPAPE HSNNPLRYKF SWSPVGVLMN 670 680 690 700 710 720 VMQSATYLLD GKVVNVAGGI SFLDAVTSMD FFPGLNLEGY PNRDSTKYAE IYGISSAHTL 730 740 750 760 770 780 LRGTLRYKGY MKALNGFVKL GLINREALPA FRPEANPLTW KQLLCDLVGI SPSSEHDVLK 790 800 810 820 830 840 EAVLKKLGGD NTQLEAAEWL GLLGDEQVPQ AESILDALSK HLVMKLSYGP EEKDMIVMRD 850 860 870 880 890 900 SFGIRHPSGH LEHKTIDLVA YGDINGFSAM AKTVGLPTAM AAKMLLDGEI GAKGLMGPFS 910 920 KEIYGPILER IKAEGIIYTT QSTIKP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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: 10775527] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION.
[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: 12853948] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF229180 mRNA. Translation: AAF44328.1. AJ007714 mRNA. Translation: CAA07619.2. AC006020 Genomic DNA. Translation: AAF03526.1.
IPI	IPI00033217.
RefSeq	NP_005754.2.
UniGene	Hs.156738
3D structure databases
ModBase	Search...
Proteomic databases
PeptideAtlas	Q9UDR5.
PRIDE	Q9UDR5.
Genome annotation databases
Ensembl	ENSG00000008311. Homo sapiens. [Contig view]
GeneID	10157.
KEGG	hsa:10157.
Organism-specific databases
GeneCards	GC07M121503.
HGNC	HGNC:17366. AASS.
MIM	238700. phenotype. 605113. gene.
Orphanet	2203. Hyperlysinemia. 3124. Saccharopinuria.
PharmGKB	PA24369.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q9UDR5.
HOVERGEN	Q9UDR5.
OMA	Q9UDR5. DNPLRYK.
Enzyme and pathway databases
BioCyc	MetaCyc:MON-12249.
BRENDA	1.5.1.8. 247. 1.5.1.9. 247.
Reactome	REACT_13. Metabolism of amino acids.
Gene expression databases
ArrayExpress	Q9UDR5.
Bgee	Q9UDR5.
CleanEx	HS_AASS.
GermOnline	ENSG00000008311. Homo sapiens.
Family and domain databases
InterPro	IPR007698. Ala_DH/PNT_C. IPR008142. Ala_DH/PNT_CS1. IPR008143. Ala_DH/PNT_CS2. IPR007886. Ala_DH/PNT_N. IPR005097. Saccharopine_DH. [Graphical view]
Pfam	PF01262. AlaDh_PNT_C. 1 hit. PF05222. AlaDh_PNT_N. 1 hit. PF03435. Saccharop_dh. 1 hit. [Graphical view]
PROSITE	PS00836. ALADH_PNT_1. False negative. PS00837. ALADH_PNT_2. False negative. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB00142. L-Glutamic Acid. DB00157. NADH.
NextBio	38452.
SOURCE	Search...

Entry information

Entry name

AASS_HUMAN

Accession

Primary (citable) accession number: Q9UDR5
Secondary accession number(s): O95462

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 13, 2004
Last sequence update:	May 1, 2000
Last modified:	June 16, 2009
This is version 63 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)