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Identification
HMDB Protein ID HMDBP01060
Secondary Accession Numbers
  • 6349
Name Delta-aminolevulinic acid dehydratase
Synonyms
  1. ALADH
  2. Porphobilinogen synthase
Gene Name ALAD
Protein Type Unknown
Biological Properties
General Function Involved in porphobilinogen synthase activity
Specific 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.
Pathways
  • Acute Intermittent Porphyria
  • Congenital Erythropoietic Porphyria (CEP) or Gunther Disease
  • Hereditary Coproporphyria (HCP)
  • Porphyria Variegata (PV)
  • Porphyrin and chlorophyll metabolism
  • Porphyrin Metabolism
  • protoporphyrin-IX biosynthesis
Reactions
5-Aminolevulinic acid → Porphobilinogen + Water details
GO Classification
Biological Process
small molecule metabolic process
heme biosynthetic process
protoporphyrinogen IX biosynthetic process
protein homooligomerization
Cellular Component
cytosol
Function
ion binding
cation binding
metal ion binding
binding
catalytic activity
lyase activity
carbon-oxygen lyase activity
hydro-lyase activity
porphobilinogen synthase activity
Molecular Function
zinc ion binding
lead ion binding
porphobilinogen synthase activity
Process
metabolic process
biosynthetic process
cellular biosynthetic process
heterocycle biosynthetic process
tetrapyrrole biosynthetic process
Cellular Location Not Available
Gene Properties
Chromosome Location 9
Locus 9q33.1
SNPs ALAD
Gene Sequence
>993 bp
ATGCAGCCCCAGTCCGTTCTGCACAGCGGCTACTTCCACCCACTACTTCGGGCCTGGCAG
ACAGCCACCACCACCCTCAATGCCTCCAACCTCATCTACCCCATCTTTGTCACGGATGTT
CCTGATGACATACAGCCTATCACCAGCCTCCCAGGAGTGGCCAGGTATGGTGTGAAGCGG
CTGGAAGAGATGCTGAGGCCCTTGGTGGAAGAGGGCCTACGCTGTGTCTTGATCTTTGGC
GTCCCCAGCAGAGTTCCCAAGGACGAGCGGGGTTCCGCAGCTGACTCCGAGGAGTCCCCA
GCTATTGAGGCAATCCATCTGTTGAGGAAGACCTTCCCCAACCTCCTGGTGGCCTGTGAT
GTCTGCCTGTGTCCCTACACCTCCCATGGTCACTGCGGGCTCCTGAGTGAAAACGGAGCA
TTCCGGGCTGAGGAGAGCCGCCAGCGGCTGGCTGAGGTGGCATTGGCGTATGCCAAGGCA
GGATGTCAGGTGGTAGCCCCGTCGGACATGATGGATGGACGCGTGGAAGCCATCAAAGAG
GCCCTGATGGCACATGGACTTGGCAACAGGGTATCGGTGATGAGCTACAGTGCCAAATTT
GCTTCCTGTTTCTATGGCCCTTTCCGGGATGCAGCTAAGTCAAGCCCAGCTTTTGGGGAC
CGCCGCTGCTACCAGCTGCCCCCTGGAGCACGAGGCCTGGCTCTCCGAGCTGTGGACCGG
GATGTACGGGAAGGAGCTGACATGCTCATGGTGAAGCCGGGAATGCCCTACCTGGACATC
GTGCGGGAGGTAAAGGACAAGCACCCTGACCTCCCTCTCGCCGTGTACCACGTCTCTGGA
GAGTTTGCCATGCTGTGGCATGGAGCCCAGGCCGGGGCATTTGATCTCAAGGCTGCCGTA
CTGGAGGCCATGACTGCCTTCCGCAGAGCAGGTGCTGACATCATCATCACCTACTACACA
CCGCAGCTGCTGCAGTGGCTGAAGGAGGAATGA
Protein Properties
Number of Residues 330
Molecular Weight 36294.485
Theoretical pI 6.786
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Delta-aminolevulinic acid dehydratase
MQPQSVLHSGYFHPLLRAWQTATTTLNASNLIYPIFVTDVPDDIQPITSLPGVARYGVKR
LEEMLRPLVEEGLRCVLIFGVPSRVPKDERGSAADSEESPAIEAIHLLRKTFPNLLVACD
VCLCPYTSHGHCGLLSENGAFRAEESRQRLAEVALAYAKAGCQVVAPSDMMDGRVEAIKE
ALMAHGLGNRVSVMSYSAKFASCFYGPFRDAAKSSPAFGDRRCYQLPPGARGLALRAVDR
DVREGADMLMVKPGMPYLDIVREVKDKHPDLPLAVYHVSGEFAMLWHGAQAGAFDLKAAV
LEAMTAFRRAGADIIITYYTPQLLQWLKEE
GenBank ID Protein 178329
UniProtKB/Swiss-Prot ID P13716
UniProtKB/Swiss-Prot Entry Name HEM2_HUMAN
PDB IDs
GenBank Gene ID M13928
GeneCard ID ALAD
GenAtlas ID ALAD
HGNC ID HGNC:395
References
General References
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  5. Akagi R, Inoue R, Muranaka S, Tahara T, Taketani S, Anderson KE, Phillips JD, Sassa S: Dual gene defects involving delta-aminolaevulinate dehydratase and coproporphyrinogen oxidase in a porphyria patient. Br J Haematol. 2006 Jan;132(2):237-43. [PubMed:16398658 ]
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  7. Astrin KH, Kaya AH, Wetmur JG, Desnick RJ: RsaI polymorphism in the human delta-aminolevulinate dehydratase gene at 9q34. Nucleic Acids Res. 1991 Aug 11;19(15):4307. [PubMed:1678509 ]
  8. Ishida N, Fujita H, Fukuda Y, Noguchi T, Doss M, Kappas A, Sassa S: Cloning and expression of the defective genes from a patient with delta-aminolevulinate dehydratase porphyria. J Clin Invest. 1992 May;89(5):1431-7. [PubMed:1569184 ]
  9. Gibbs PN, Jordan PM: Identification of lysine at the active site of human 5-aminolaevulinate dehydratase. Biochem J. 1986 Jun 1;236(2):447-51. [PubMed:3092810 ]
  10. Jaffe EK, Martins J, Li J, Kervinen J, Dunbrack RL Jr: The molecular mechanism of lead inhibition of human porphobilinogen synthase. J Biol Chem. 2001 Jan 12;276(2):1531-7. [PubMed:11032836 ]
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  13. Wetmur JG, Kaya AH, Plewinska M, Desnick RJ: Molecular characterization of the human delta-aminolevulinate dehydratase 2 (ALAD2) allele: implications for molecular screening of individuals for genetic susceptibility to lead poisoning. Am J Hum Genet. 1991 Oct;49(4):757-63. [PubMed:1716854 ]
  14. Plewinska M, Thunell S, Holmberg L, Wetmur JG, Desnick RJ: delta-Aminolevulinate dehydratase deficient porphyria: identification of the molecular lesions in a severely affected homozygote. Am J Hum Genet. 1991 Jul;49(1):167-74. [PubMed:2063868 ]
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  18. Jaffe EK, Stith L: ALAD porphyria is a conformational disease. Am J Hum Genet. 2007 Feb;80(2):329-37. Epub 2006 Dec 21. [PubMed:17236137 ]