Delta-aminolevulinic acid dehydratase

Details

Name
Delta-aminolevulinic acid dehydratase
Synonyms
  • 4.2.1.24
  • ALADH
  • Porphobilinogen synthase
Gene Name
ALAD
Organism
Humans
Amino acid sequence
>lcl|BSEQ0000100|Delta-aminolevulinic acid dehydratase
MQPQSVLHSGYFHPLLRAWQTATTTLNASNLIYPIFVTDVPDDIQPITSLPGVARYGVKR
LEEMLRPLVEEGLRCVLIFGVPSRVPKDERGSAADSEESPAIEAIHLLRKTFPNLLVACD
VCLCPYTSHGHCGLLSENGAFRAEESRQRLAEVALAYAKAGCQVVAPSDMMDGRVEAIKE
ALMAHGLGNRVSVMSYSAKFASCFYGPFRDAAKSSPAFGDRRCYQLPPGARGLALRAVDR
DVREGADMLMVKPGMPYLDIVREVKDKHPDLPLAVYHVSGEFAMLWHGAQAGAFDLKAAV
LEAMTAFRRAGADIIITYYTPQLLQWLKEE
Number of residues
330
Molecular Weight
36294.485
Theoretical pI
6.78
GO Classification
Functions
catalytic activity / identical protein binding / lead ion binding / porphobilinogen synthase activity / zinc ion binding
Processes
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
Components
cytosol / extracellular exosome / extracellular space / nucleus
General Function
Zinc ion binding
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.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Not Available
Gene sequence
>lcl|BSEQ0010142|Delta-aminolevulinic acid dehydratase (ALAD)
ATGCAGCCCCAGTCCGTTCTGCACAGCGGCTACTTCCACCCACTACTTCGGGCCTGGCAG
ACAGCCACCACCACCCTCAATGCCTCCAACCTCATCTACCCCATCTTTGTCACGGATGTT
CCTGATGACATACAGCCTATCACCAGCCTCCCAGGAGTGGCCAGGTATGGTGTGAAGCGG
CTGGAAGAGATGCTGAGGCCCTTGGTGGAAGAGGGCCTACGCTGTGTCTTGATCTTTGGC
GTCCCCAGCAGAGTTCCCAAGGACGAGCGGGGTTCCGCAGCTGACTCCGAGGAGTCCCCA
GCTATTGAGGCAATCCATCTGTTGAGGAAGACCTTCCCCAACCTCCTGGTGGCCTGTGAT
GTCTGCCTGTGTCCCTACACCTCCCATGGTCACTGCGGGCTCCTGAGTGAAAACGGAGCA
TTCCGGGCTGAGGAGAGCCGCCAGCGGCTGGCTGAGGTGGCATTGGCGTATGCCAAGGCA
GGATGTCAGGTGGTAGCCCCGTCGGACATGATGGATGGACGCGTGGAAGCCATCAAAGAG
GCCCTGATGGCACATGGACTTGGCAACAGGGTATCGGTGATGAGCTACAGTGCCAAATTT
GCTTCCTGTTTCTATGGCCCTTTCCGGGATGCAGCTAAGTCAAGCCCAGCTTTTGGGGAC
CGCCGCTGCTACCAGCTGCCCCCTGGAGCACGAGGCCTGGCTCTCCGAGCTGTGGACCGG
GATGTACGGGAAGGAGCTGACATGCTCATGGTGAAGCCGGGAATGCCCTACCTGGACATC
GTGCGGGAGGTAAAGGACAAGCACCCTGACCTCCCTCTCGCCGTGTACCACGTCTCTGGA
GAGTTTGCCATGCTGTGGCATGGAGCCCAGGCCGGGGCATTTGATCTCAAGGCTGCCGTA
CTGGAGGCCATGACTGCCTTCCGCAGAGCAGGTGCTGACATCATCATCACCTACTACACA
CCGCAGCTGCTGCAGTGGCTGAAGGAGGAATGA
Chromosome Location
9
Locus
9q33.1
External Identifiers
ResourceLink
UniProtKB IDP13716
UniProtKB Entry NameHEM2_HUMAN
GenBank Protein ID178329
GenBank Gene IDM13928
GenAtlas IDALAD
HGNC IDHGNC:395
General References
  1. Wetmur JG, Bishop DF, Cantelmo C, Desnick RJ: Human delta-aminolevulinate dehydratase: nucleotide sequence of a full-length cDNA clone. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7703-7. [PubMed:3463993]
  2. 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]
  3. 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]
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  8. 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]
  9. 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]
  10. Lawrence SH, Ramirez UD, Selwood T, Stith L, Jaffe EK: Allosteric inhibition of human porphobilinogen synthase. J Biol Chem. 2009 Dec 18;284(51):35807-17. doi: 10.1074/jbc.M109.026294. Epub . [PubMed:19812033]
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  12. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [PubMed:24275569]
  13. Breinig S, Kervinen J, Stith L, Wasson AS, Fairman R, Wlodawer A, Zdanov A, Jaffe EK: Control of tetrapyrrole biosynthesis by alternate quaternary forms of porphobilinogen synthase. Nat Struct Biol. 2003 Sep;10(9):757-63. Epub 2003 Aug 3. [PubMed:12897770]
  14. 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]
  15. 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]
  16. Sassa S, Ishida N, Fujita H, Fukuda Y, Noguchi T, Doss M, Kappas A: Cloning and expression of the defective genes in delta-aminolevulinate dehydratase porphyria: compound heterozygosity in this hereditary liver disease. Trans Assoc Am Physicians. 1992;105:250-9. [PubMed:1309003]
  17. Akagi R, Yasui Y, Harper P, Sassa S: A novel mutation of delta-aminolaevulinate dehydratase in a healthy child with 12% erythrocyte enzyme activity. Br J Haematol. 1999 Sep;106(4):931-7. [PubMed:10519994]
  18. Akagi R, Shimizu R, Furuyama K, Doss MO, Sassa S: Novel molecular defects of the delta-aminolevulinate dehydratase gene in a patient with inherited acute hepatic porphyria. Hepatology. 2000 Mar;31(3):704-8. [PubMed:10706561]
  19. 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]
  20. 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]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00855Aminolevulinic acidapprovedyesinducerDetails
DB02068Delta-Amino Valeric AcidexperimentalunknownDetails
DB02239Laevulinic AcidexperimentalunknownDetails
DB02272PorphobilinogenexperimentalunknownDetails
DB028783-(2-Aminoethyl)-4-(Aminomethyl)Heptanedioic AcidexperimentalunknownDetails
DB047815-hydroxyvaleric acidexperimentalunknownDetails
DB022604-Oxosebacic AcidexperimentalunknownDetails
DB045604,7-Dioxosebacic AcidexperimentalunknownDetails