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P06214 (HEM2_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 115. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Delta-aminolevulinic acid dehydratase

Short name=ALADH
EC=4.2.1.24
Alternative name(s):
Porphobilinogen synthase
Gene names
Name:Alad
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length330 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalyzes an early step in the biosynthesis of tetrapyrroles. Binds two molecules of 5-aminolevulinate per subunit, each at a distinct site, and catalyzes their condensation to form porphobilinogen By similarity.

Catalytic activity

2 5-aminolevulinate = porphobilinogen + 2 H2O.

Cofactor

Binds 8 zinc ions per octamer. Requires four zinc ions per octamer for full catalytic activity. Can bind up to 2 zinc ions per subunit By similarity.

Enzyme regulation

Can alternate between a fully active homooctamer and a low-activity homohexamer. A bound magnesium ion may promote the assembly of the fully active homooctamer. The magnesium-binding site is absent in the low-activity homohexamer. Inhibited by compounds that favor the hexameric state. Inhibited by divalent lead ions. The lead ions partially displace the zinc cofactor By similarity.

Pathway

Porphyrin-containing compound metabolism; protoporphyrin-IX biosynthesis; coproporphyrinogen-III from 5-aminolevulinate: step 1/4.

Subunit structure

Homooctamer; active form. Homohexamer; low activity form By similarity.

Sequence similarities

Belongs to the ALADH family.

Ontologies

Keywords
   Biological processHeme biosynthesis
Porphyrin biosynthesis
   LigandMetal-binding
Zinc
   Molecular functionLyase
   PTMPhosphoprotein
   Technical termAllosteric enzyme
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processcellular response to lead ion

Inferred from expression pattern PubMed 16566714. Source: RGD

heme biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

protoporphyrinogen IX biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-UniPathway

response to activity

Inferred from expression pattern PubMed 12171438. Source: RGD

response to aluminum ion

Inferred from expression pattern PubMed 518129. Source: RGD

response to amino acid

Inferred from expression pattern PubMed 8295845. Source: RGD

response to arsenic-containing substance

Inferred from direct assay PubMed 17086449. Source: RGD

response to cadmium ion

Inferred from direct assay PubMed 7896311. Source: RGD

response to cobalt ion

Inferred from expression pattern PubMed 826600. Source: RGD

response to drug

Inferred from direct assay PubMed 8070841. Source: RGD

response to ethanol

Inferred from direct assay PubMed 2394940. Source: RGD

response to fatty acid

Inferred from expression pattern PubMed 20026167. Source: RGD

response to glucocorticoid

Inferred from expression pattern PubMed 12596873. Source: RGD

response to herbicide

Inferred from expression pattern PubMed 12180188. Source: RGD

response to hormone

Inferred from expression pattern PubMed 17720948PubMed 9468112. Source: RGD

response to hypoxia

Inferred from expression pattern PubMed 3697363. Source: RGD

response to inorganic substance

Inferred from expression pattern PubMed 19743388. Source: RGD

response to ionizing radiation

Inferred from expression pattern PubMed 17916974. Source: RGD

response to iron ion

Inferred from expression pattern PubMed 14598909. Source: RGD

response to lead ion

Inferred from expression pattern PubMed 16597373. Source: RGD

response to lipopolysaccharide

Inferred from expression pattern PubMed 19344711. Source: RGD

response to mercury ion

Inferred from expression pattern PubMed 17881112. Source: RGD

response to metal ion

Inferred from direct assay PubMed 15302091. Source: RGD

response to methylmercury

Inferred from expression pattern PubMed 19874286. Source: RGD

response to nutrient

Inferred from direct assay PubMed 2394940. Source: RGD

response to nutrient levels

Inferred from expression pattern PubMed 8000239. Source: RGD

response to organic cyclic compound

Inferred from expression pattern PubMed 19647414. Source: RGD

response to organic substance

Inferred from direct assay PubMed 12853123PubMed 826600. Source: RGD

response to oxidative stress

Inferred from expression pattern PubMed 17916976. Source: RGD

response to platinum ion

Inferred from expression pattern PubMed 925603. Source: RGD

response to selenium ion

Inferred from expression pattern PubMed 15721883. Source: RGD

response to toxic substance

Inferred from expression pattern PubMed 20517888. Source: RGD

response to vitamin

Inferred from expression pattern PubMed 9559098. Source: RGD

response to vitamin B1

Inferred from expression pattern PubMed 20088549. Source: RGD

response to vitamin E

Inferred from expression pattern PubMed 17572058. Source: RGD

response to zinc ion

Inferred from direct assay PubMed 3987589. Source: RGD

   Cellular_componentcytosol

Inferred from direct assay PubMed 2394940. Source: RGD

extracellular space

Inferred from direct assay PubMed 19111884. Source: RGD

   Molecular_functionlead ion binding

Inferred from sequence or structural similarity. Source: UniProtKB

porphobilinogen synthase activity

Inferred from sequence or structural similarity. Source: UniProtKB

zinc ion binding

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 330330Delta-aminolevulinic acid dehydratase
PRO_0000140530

Sites

Active site1991Schiff-base intermediate with substrate By similarity
Active site2521Schiff-base intermediate with substrate By similarity
Metal binding1221Zinc 1; catalytic By similarity
Metal binding1241Zinc 1; catalytic By similarity
Metal binding1311Zinc 2 By similarity
Metal binding1321Zinc 1; catalytic By similarity
Metal binding2231Zinc 2 By similarity
Binding site2091Substrate 1 By similarity
Binding site2211Substrate 1 By similarity
Binding site2791Substrate 2 By similarity
Binding site3181Substrate 2 By similarity

Amino acid modifications

Modified residue1991N6-succinyllysine By similarity
Modified residue2151Phosphoserine By similarity
Modified residue2521N6-succinyllysine By similarity

Sequences

Sequence LengthMass (Da)Tools
P06214 [UniParc].

Last modified January 1, 1988. Version 1.
Checksum: 617F6E85B647AB25

FASTA33036,032
        10         20         30         40         50         60 
MHHQSVLHSG YFHPLLRAWQ TTPSTVSATN LIYPIFVTDV PDDVQPIASL PGVARYGVNQ 

        70         80         90        100        110        120 
LEEMLRPLVE AGLRCVLIFG VPSRVPKDEQ GSAADSEDSP TIEAVRLLRK TFPTLLVACD 

       130        140        150        160        170        180 
VCLCPYTSHG HCGLLSENGA FLAEESRQRL AEVALAYAKA GCQVVAPSDM MDGRVEAIKA 

       190        200        210        220        230        240 
ALLKHGLGNR VSVMSYSAKF ASCFYGPFRD AAQSSPAFGD RRCYQLPPGA RGLALRAVAR 

       250        260        270        280        290        300 
DIQEGADILM VKPGLPYLDM VQEVKDKHPE LPLAVYQVSG EFAMLWHGAK AGAFDLRTAV 

       310        320        330 
LESMTAFRRA GADIIITYFA PQLLKWLKEE 

« Hide

References

« Hide 'large scale' references
[1]"Nucleotide sequence of rat liver delta-aminolevulinic acid dehydratase cDNA."
Bishop T.R., Frelin L.P., Boyer S.H.
Nucleic Acids Res. 14:10115-10115(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Liver.
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Prostate.
[3]"Isolation of a rat liver delta-aminolevulinate dehydrase (ALAD) cDNA clone: evidence for unequal ALAD gene dosage among inbred mouse strains."
Bishop T.R., Cohen P.J., Boyer S.H., Noyes A.N., Frelin L.P.
Proc. Natl. Acad. Sci. U.S.A. 83:5568-5572(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-45.
[4]Lubec G., Afjehi-Sadat L.
Submitted (NOV-2006) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 56-84 AND 200-209, IDENTIFICATION BY MASS SPECTROMETRY.
Strain: Sprague-Dawley.
Tissue: Spinal cord.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X04959 mRNA. Translation: CAA28621.1.
BC061806 mRNA. Translation: AAH61806.1.
PIRA24724.
RefSeqNP_037031.1. NM_012899.2.
XP_006238296.1. XM_006238234.1.
XP_006238297.1. XM_006238235.1.
UniGeneRn.3941.

3D structure databases

ProteinModelPortalP06214.
SMRP06214. Positions 5-328.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid247413. 1 interaction.
MINTMINT-4567662.
STRING10116.ENSRNOP00000020625.

PTM databases

PhosphoSiteP06214.

Proteomic databases

PaxDbP06214.
PRIDEP06214.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000020625; ENSRNOP00000020625; ENSRNOG00000015206.
GeneID25374.
KEGGrno:25374.
UCSCRGD:2083. rat.

Organism-specific databases

CTD210.
RGD2083. Alad.

Phylogenomic databases

eggNOGCOG0113.
GeneTreeENSGT00390000006998.
HOGENOMHOG000020323.
HOVERGENHBG001222.
InParanoidP06214.
KOK01698.
OMAIITYFTP.
OrthoDBEOG751NFP.
PhylomeDBP06214.
TreeFamTF300665.

Enzyme and pathway databases

UniPathwayUPA00251; UER00318.

Gene expression databases

GenevestigatorP06214.

Family and domain databases

Gene3D3.20.20.70. 1 hit.
InterProIPR013785. Aldolase_TIM.
IPR001731. Porphobilinogen_synth.
[Graphical view]
PANTHERPTHR11458. PTHR11458. 1 hit.
PfamPF00490. ALAD. 1 hit.
[Graphical view]
PIRSFPIRSF001415. Porphbilin_synth. 1 hit.
PRINTSPR00144. DALDHYDRTASE.
SMARTSM01004. ALAD. 1 hit.
[Graphical view]
PROSITEPS00169. D_ALA_DEHYDRATASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio606397.
PROP06214.

Entry information

Entry nameHEM2_RAT
AccessionPrimary (citable) accession number: P06214
Entry history
Integrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: January 1, 1988
Last modified: April 16, 2014
This is version 115 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways