Aspartate-semialdehyde dehydrogenase - Escherichia coli (strain K12)

Contribute

Send feedback

Read comments (?) or add your own

P0A9Q9 (DHAS_ECOLI) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 68. History...

Clusters with 100%, 90%, 50% identity |

Documents (4) |

Third-party data

text xml rdf/xml gff fasta

Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Aspartate-semialdehyde dehydrogenase
Short name=ASA dehydrogenase
Short name=ASADH
EC=1.2.1.11

Alternative name(s):
Aspartate-beta-semialdehyde dehydrogenase

Gene names

Name:	asd
Synonyms:	hom
Ordered Locus Names:	b3433, JW3396

Organism

Escherichia coli (strain K12)

Taxonomic identifier

83333 [NCBI]

Taxonomic lineage

Bacteria › Proteobacteria › Gammaproteobacteria › Enterobacteriales › Enterobacteriaceae › Escherichia

Protein attributes

Sequence length	367 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the NADPH-dependent formation of L-aspartate-semialdehyde (L-ASA) by the reductive dephosphorylation of L-aspartyl-4-phosphate. Ref.4 Ref.7
Catalytic activity	L-aspartate 4-semialdehyde + phosphate + NADP⁺ = L-4-aspartyl phosphate + NADPH. Ref.4 Ref.7
Enzyme regulation	Is inhibited by L- and D-cystine, and by other cystine derivatives, via the formation of a covalently bound cysteine at the active site Cys-135. Ref.8
Pathway	Amino-acid biosynthesis; L-lysine biosynthesis via DAP pathway; (S)-tetrahydrodipicolinate from L-aspartate: step 2/4. HAMAP MF_02121 Amino-acid biosynthesis; L-methionine biosynthesis via de novo pathway; L-homoserine from L-aspartate: step 2/3. HAMAP MF_02121 Amino-acid biosynthesis; L-threonine biosynthesis; L-threonine from L-aspartate: step 2/5. HAMAP MF_02121
Subunit structure	Homodimer. Ref.4
Domain	Consists of two domains, an N-terminal nucleotide-binding domain and a C-terminal dimerization domain. Ref.9
Sequence similarities	Belongs to the aspartate-semialdehyde dehydrogenase family.
Biophysicochemical properties	Kinetic parameters: K_M=22 µM for L-4-aspartyl phosphate Ref.7 K_M=29 µM for NADPH K_M=110 µM for L-aspartate 4-semialdehyde K_M=144 µM for NADP⁺ K_M=10.2 mM for phosphate

Ontologies

Keywords
Biological process	Amino-acid biosynthesis Diaminopimelate biosynthesis Lysine biosynthesis Methionine biosynthesis Threonine biosynthesis
Ligand	NADP
Molecular function	Oxidoreductase
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	diaminopimelate biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW homoserine biosynthetic process Inferred from direct assay Ref.8. Source: EcoCyc isoleucine biosynthetic process Inferred from electronic annotation. Source: InterPro methionine biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW threonine biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from electronic annotation. Source: InterPro
Molecular function	N-acetyl-gamma-glutamyl-phosphate reductase activity Inferred from electronic annotation. Source: InterPro NAD binding Inferred from electronic annotation. Source: InterPro NADP binding Inferred from electronic annotation. Source: InterPro aspartate-semialdehyde dehydrogenase activity Inferred from direct assay Ref.8. Source: EcoCyc protein dimerization activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
dnaK	P0A6Y8	1	EBI-1132825,EBI-542092

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 367

367

Aspartate-semialdehyde dehydrogenase HAMAP MF_02121

PRO_0000141369

Regions

Nucleotide binding

10 – 13

NADP HAMAP MF_02121

Nucleotide binding

37 – 38

NADP HAMAP MF_02121

Nucleotide binding

165 – 169

NADP HAMAP MF_02121

Sites

Active site

135

Acyl-thioester intermediate Ref.6 Ref.10

Active site

274

Proton acceptor Ref.6 Ref.10

Binding site

NADP

Binding site

102

Phosphate By similarity

Binding site

162

Substrate

Binding site

173

NADP

Binding site

193

NADP; via carbonyl oxygen

Binding site

241

Substrate

Binding site

244

Phosphate By similarity

Binding site

267

Substrate

Binding site

350

NADP

Amino acid modifications

Modified residue

135

S-cysteinyl cysteine; in inhibited form HAMAP MF_02121

Experimental info

Mutagenesis

135

C → A: Complete loss of activity. Ref.6

Mutagenesis

135

C → S: 99.7% loss of activity. Ref.6

Sequence conflict

W → G AA sequence Ref.5

Secondary structure

367

Helix Strand Turn

Details...

Sequences

Sequence

Length

Mass (Da)

Tools

P0A9Q9 [UniParc].

Last modified July 21, 1986. Version 1.
Checksum: F53D4C36EA7CC201
Show »

FASTA

367

40,018

        10         20         30         40         50         60 
MKNVGFIGWR GMVGSVLMQR MVEERDFDAI RPVFFSTSQL GQAAPSFGGT TGTLQDAFDL 

        70         80         90        100        110        120 
EALKALDIIV TCQGGDYTNE IYPKLRESGW QGYWIDAASS LRMKDDAIII LDPVNQDVIT 

       130        140        150        160        170        180 
DGLNNGIRTF VGGNCTVSLM LMSLGGLFAN DLVDWVSVAT YQAASGGGAR HMRELLTQMG 

       190        200        210        220        230        240 
HLYGHVADEL ATPSSAILDI ERKVTTLTRS GELPVDNFGV PLAGSLIPWI DKQLDNGQSR 

       250        260        270        280        290        300 
EEWKGQAETN KILNTSSVIP VDGLCVRVGA LRCHSQAFTI KLKKDVSIPT VEELLAAHNP 

       310        320        330        340        350        360 
WAKVVPNDRE ITMRELTPAA VTGTLTTPVG RLRKLNMGPE FLSAFTVGDQ LLWGAAEPLR 


RMLRQLA

« Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Nucleotide sequence of the asd gene of Escherichia coli: absence of a typical attenuation signal." Haziza C., Stragier P., Patte J.-C. EMBO J. 1:379-384(1982) [PubMed: 6143662] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"The complete genome sequence of Escherichia coli K-12." Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V., Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F., Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B., Shao Y. Science 277:1453-1474(1997) [PubMed: 9278503] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: K12 / MG1655 / ATCC 47076.
[3]	"Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110." Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S., Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T. Mol. Syst. Biol. 2:E1-E5(2006) [PubMed: 16738553] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[4]	"Aspartate-beta-semialdehyde dehydrogenase from Escherichia coli. Purification and general properties." Biellmann J.F., Eid P., Hirth C., Jornvall H. Eur. J. Biochem. 104:53-58(1980) [PubMed: 6102909] [Abstract] Cited for: PROTEIN SEQUENCE OF 1-5, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT. Strain: K12.
[5]	"Comparing the predicted and observed properties of proteins encoded in the genome of Escherichia coli K-12." Link A.J., Robison K., Church G.M. Electrophoresis 18:1259-1313(1997) [PubMed: 9298646] [Abstract] Cited for: PROTEIN SEQUENCE OF 1-12. Strain: K12 / EMG2.
[6]	"Identification of an essential cysteine in the reaction catalyzed by aspartate-beta-semialdehyde dehydrogenase from Escherichia coli." Karsten W.E., Viola R.E. Biochim. Biophys. Acta 1121:234-238(1992) [PubMed: 1350921] [Abstract] Cited for: ACTIVE SITE, MUTAGENESIS OF CYS-135.
[7]	"An integrated study of threonine-pathway enzyme kinetics in Escherichia coli." Chassagnole C., Rais B., Quentin E., Fell D.A., Mazat J.P. Biochem. J. 356:415-423(2001) [PubMed: 11368768] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, KINETIC PARAMETERS.
[8]	"L-cystine inhibits aspartate-beta-semialdehyde dehydrogenase by covalently binding to the essential 135Cys of the enzyme." Alvarez E., Ramon F., Magan C., Diez E. Biochim. Biophys. Acta 1696:23-29(2004) [PubMed: 14726201] [Abstract] Cited for: ENZYME REGULATION, INHIBITION BY CYSTEINE BINDING AT CYS-135.
[9]	"Structure of aspartate-beta-semialdehyde dehydrogenase from Escherichia coli, a key enzyme in the aspartate family of amino acid biosynthesis." Hadfield A., Kryger G., Ouyang J., Petsko G.A., Ringe D., Viola R. J. Mol. Biol. 289:991-1002(1999) [PubMed: 10369777] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS), DOMAIN.
[10]	"Active site analysis of the potential antimicrobial target aspartate semialdehyde dehydrogenase." Hadfield A., Shammas C., Kryger G., Ringe D., Petsko G.A., Ouyang J., Viola R.E. Biochemistry 40:14475-14483(2001) [PubMed: 11724560] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) IN COMPLEX WITH CYSTEINE AND NADP, ACTIVE SITE, CATALYTIC MECHANISM.
[11]	"High-resolution structures reveal details of domain closure and 'half-of-sites-reactivity' in Escherichia coli aspartate beta-semialdehyde dehydrogenase." Nichols C.E., Dhaliwal B., Lockyer M., Hawkins A.R., Stammers D.K. J. Mol. Biol. 341:797-806(2004) [PubMed: 15288787] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF MUTANT GLN-2.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

V00262 Genomic DNA. Translation: CAA23511.1.
U18997 Genomic DNA. Translation: AAA58231.1.
U00096 Genomic DNA. Translation: AAC76458.1.
AP009048 Genomic DNA. Translation: BAE77859.1.

PIR

DEECDA. A00364.

RefSeq

NP_417891.1. NC_000913.2.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BRM	X-ray	2.50	A/B/C	1-367	[»]
1GL3	X-ray	2.60	A/B	1-367	[»]
1T4B	X-ray	1.60	A/B	1-367	[»]
1T4D	X-ray	1.95	A/B/C	1-367	[»]

ProteinModelPortal

P0A9Q9.

SMR

P0A9Q9. Positions 1-367.

ModBase

Search...

Protein-protein interaction databases

IntAct

P0A9Q9. 1 interaction.

PTM databases

PhosSite

P0A9Q9.

2D gel databases

SWISS-2DPAGE

P0A9Q9.

2DBase-Ecoli

P0A9Q9.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblBacteria

EBESCT00000001309; EBESCP00000001309; EBESCG00000001084.
EBESCT00000015935; EBESCP00000015226; EBESCG00000014995.

GeneID

947939.

GenomeReviews

Gene locus JW3396 in contig AP009048_GR.
Gene locus b3433 in contig U00096_GR.

KEGG

ecj:JW3396.
eco:b3433.

PATRIC

32122306. VBIEscCol129921_3530.

Organism-specific databases

EchoBASE

EB0086.

EcoGene

EG10088. asd.

Phylogenomic databases

eggNOG

COG0136.

GeneTree

EBGT00050000010426.

HOGENOM

HBG289760.

OMA

IDGLCVR.

PhylomeDB

P0A9Q9.

ProtClustDB

PRK06598.

Enzyme and pathway databases

BioCyc

EcoCyc:ASP-SEMIALDEHYDE-DEHYDROGENASE-MONOMER.
MetaCyc:ASP-SEMIALDEHYDE-DEHYDROGENASE-MONOMER.

Gene expression databases

Genevestigator

P0A9Q9.

Family and domain databases

HAMAP

MF_02121. ASADH.
[Tree]

InterPro

IPR000319. Asp-semialdehyde_DH_CS.
IPR011534. Asp_ADH_gamma-type.
IPR012080. Asp_semialdehyde_DH.
IPR016040. NAD(P)-bd_dom.
IPR000534. Semialdehyde_DH_NAD-bd.
IPR012280. Semialdhyde_DH_dimer_dom.
[Graphical view]

Gene3D

G3DSA:3.40.50.720. NAD(P)-bd. 1 hit.

K00133.

Pfam

PF01118. Semialdhyde_dh. 1 hit.
PF02774. Semialdhyde_dhC. 1 hit.
[Graphical view]

PIRSF

PIRSF000148. ASA_dh. 1 hit.

SMART

SM00859. Semialdhyde_dh. 1 hit.
[Graphical view]

TIGRFAMs

TIGR01745. Asd_gamma. 1 hit.

PROSITE

PS01103. ASD. 1 hit.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

DHAS_ECOLI

Accession

Primary (citable) accession number: P0A9Q9
Secondary accession number(s): P00353, Q2M797

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	January 25, 2012
This is version 68 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program

Relevant documents

Escherichia coli

Escherichia coli (strain K12): entries and cross-references to EcoGene

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

Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Experimental info

Secondary structure

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

2D gel databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Entry information

Relevant documents