Delta-aminolevulinic acid dehydratase

Details

Name
Delta-aminolevulinic acid dehydratase
Kind
protein
Synonyms
  • 4.2.1.24
  • ALADH
  • Porphobilinogen synthase
Gene Name
ALAD
UniProtKB Entry
P13716Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
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
proteasome core complex binding
Processes
heme A biosynthetic process / heme B biosynthetic process / heme O biosynthetic process / negative regulation of proteasomal protein catabolic process / response to xenobiotic stimulus
Components
extracellular region / ficolin-1-rich granule lumen / secretory granule lumen
General 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
Specific Function
Catalytic activity
Pfam Domain Function
Signal Regions
Not Available
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
9q32
External Identifiers
ResourceLink
UniProtKB IDP13716
UniProtKB Entry NameHEM2_HUMAN
GenBank Protein ID178329
GenBank Gene IDM13928
GeneCard IDALAD
GenAtlas IDALAD
HGNC IDHGNC:395
PDB ID(s)1E51, 1PV8, 5HMS, 5HNR
KEGG IDhsa:210
NCBI Gene ID210
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. [Article]
  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. [Article]
  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. [Article]
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  7. Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J: Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. Nat Biotechnol. 2003 May;21(5):566-9. Epub 2003 Mar 31. [Article]
  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. [Article]
  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. [Article]
  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 . [Article]
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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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]

Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Aminolevulinic acidapprovedyestargetinducerDetails
Delta-Amino Valeric AcidexperimentalyestargetinhibitorDetails
Laevulinic AcidexperimentalyestargetinhibitorDetails
PorphobilinogenexperimentalyestargetinhibitorDetails
3-(2-Aminoethyl)-4-(Aminomethyl)Heptanedioic AcidexperimentalyestargetinhibitorDetails
5-hydroxyvaleric acidexperimentalyestargetinhibitorDetails
4-Oxosebacic AcidexperimentalyestargetinhibitorDetails
4,7-Dioxosebacic AcidexperimentalyestargetinhibitorDetails
5-Fluorolevulinic AcidexperimentalyestargetinhibitorDetails
S,S-(2-Hydroxyethyl)ThiocysteineexperimentalyestargetinhibitorDetails
Formic acidexperimental, investigationalyestargetinhibitorDetails
MercaptoethanolexperimentalyestargetinhibitorDetails