Names & Taxonomy
- Uniprot ID:
- P13716
- Entry Name:
- HEM2_HUMAN
- Status:
- reviewed
- Protein Names:
- Delta-aminolevulinic acid dehydratase (ALADH) (EC 4.2.1.24) (Porphobilinogen synthase)
- Gene Names:
- ALAD
- Gene Names Primary:
- ALAD
- Organism:
- Homo sapiens (Human)
Structure
- Length:
- 330
- Sequence:
- MQPQSVLHSGYFHPLLRAWQTATTTLNASNLIYPIFVTDVPDDIQPITSLPGVARYGVKRLEEMLRPLVEEGLRCVLIFGVPSRVPKDERGSAADSEESPAIEAIHLLRKTFPNLLVACDVCLCPYTSHGHCGLLSENGAFRAEESRQRLAEVALAYAKAGCQVVAPSDMMDGRVEAIKEALMAHGLGNRVSVMSYSAKFASCFYGPFRDAAKSSPAFGDRRCYQLPPGARGLALRAVDRDVREGADMLMVKPGMPYLDIVREVKDKHPDLPLAVYHVSGEFAMLWHGAQAGAFDLKAAVLEAMTAFRRAGADIIITYYTPQLLQWLKEE
- Proteomes:
- UP000005640
Function
- 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.
- Pathway:
- Porphyrin-containing compound metabolism; protoporphyrin-IX biosynthesis; coproporphyrinogen-III from 5-aminolevulinate: step 1/4.
- Catalytic Activity:
- 2 5-aminolevulinate = porphobilinogen + 2 H(2)O.
- Cofactor:
- COFACTOR: Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
- Kinetics:
- BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=0.09 mM for 5-aminolevulinate at pH 7
- Enzyme Regulation:
- 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.
- Active Site:
- ACT_SITE 199 199 Schiff-base intermediate with substrate.
- Cross Reference Drug Bank:
- DB00855
- Gene Ontology Go:
- cytosol
extracellular exosome
extracellular space
nucleus
catalytic activity
identical protein binding
lead ion binding
porphobilinogen synthase activity
zinc ion binding
cellular response to interleukin-4
cellular response to lead ion
heme biosynthetic process
porphyrin-containing compound metabolic process
protein homooligomerization
protoporphyrinogen IX biosynthetic process
response to activity
response to aluminum ion
response to amino acid
response to arsenic-containing substance
response to cadmium ion
response to cobalt ion
response to drug
response to ethanol
response to fatty acid
response to glucocorticoid
response to herbicide
response to hypoxia
response to ionizing radiation
response to iron ion
response to lipopolysaccharide
response to mercury ion
response to methylmercury
response to oxidative stress
response to platinum ion
response to selenium ion
response to vitamin B1
response to vitamin E
response to zinc ion
small molecule metabolic process - Gene Ontology Biological Process:
- cellular response to interleukin-4
cellular response to lead ion
heme biosynthetic process
porphyrin-containing compound metabolic process
protein homooligomerization
protoporphyrinogen IX biosynthetic process
response to activity
response to aluminum ion
response to amino acid
response to arsenic-containing substance
response to cadmium ion
response to cobalt ion
response to drug
response to ethanol
response to fatty acid
response to glucocorticoid
response to herbicide
response to hypoxia
response to ionizing radiation
response to iron ion
response to lipopolysaccharide
response to mercury ion
response to methylmercury
response to oxidative stress
response to platinum ion
response to selenium ion
response to vitamin B1
response to vitamin E
response to zinc ion
small molecule metabolic process - Gene Ontology Molecular Function:
- catalytic activity
identical protein binding
lead ion binding
porphobilinogen synthase activity
zinc ion binding - Gene Ontology Cellular Component:
- cytosol
extracellular exosome
extracellular space
nucleus - Keywords:
- 3D-structure
Allosteric enzyme
Alternative splicing
Complete proteome
Direct protein sequencing
Disease mutation
Heme biosynthesis
Lyase
Metal-binding
Phosphoprotein
Polymorphism
Porphyrin biosynthesis
Reference proteome
Zinc