Delta-aminolevulinic acid dehydratase (ALAD)
The protein contains 330 amino acids for an estimated molecular weight of 36295 Da.
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. (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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| Variant | Description |
|---|---|
| an asymptomatic patient with ALAD deficiency | |
| Allele ALAD*2 | |
| AHEPP | |
| AHEPP | |
| AHEPP | |
| AHEPP | |
| AHEPP |
Biological Process
Cellular response to interleukin-4
Cellular response to lead ion
Heme biosynthetic process
Negative regulation of proteasomal protein catabolic process
Neutrophil degranulation
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
The reference OMIM entry for this protein is 125270
Delta-aminolevulinate dehydratase; alad
Aladh
Porphobilinogen synthase; pbgs
DESCRIPTION
The ALAD gene encodes delta-aminolevulinate dehydratase, also known as porphobilinogen synthase (PBGS; EC 4.2.1.24), a cytosolic enzyme that catalyzes the second step in the porphyrin and heme biosynthetic pathway. It forms the monopyrrole ring porphobilinogen from 2 molecules of delta-aminolevulinate (ALA) (Ishida et al., 1992).CLONING
Wetmur et al. (1986) identified 2 cDNAs encoding ALAD which they claimed represented the first report of a cDNA clone for a human heme biosynthetic enzyme. They found that the nucleotide sequences of the 2 cDNA clones differed at either position 730 or 733 and encoded 2 different charged amino acids, which was likely the basis for the polymorphic charged isozymes of human ALAD.GENE STRUCTURE
Kaya et al. (1994) determined that the ALAD gene spans 15.9 kb and contains 2 alternative noncoding exons, 1A and 1B, and 11 coding exons, 2 through 12. The housekeeping transcript, which includes exon 1A and not 1B, was identified in a human adult liver cDNA library, while an erythroid-specific transcript, which contains exon 1B and not 1A, was detected in a human erythroleukemia cDNA library. The promoter region upstream of housekeeping exon 1A was GC-rich and contained 3 potential Sp1 elements and a CCAAT box. Further upstream, there were 3 potential GATA-1 binding sites and an AP1 site. The promoter region upstream of erythroid-specific exon 1B had several CACCC boxes and 2 potential GATA-1 binding sites. Kaya et al. (1994) transduced HeLa and K562 cells with chloramphenicol acetyltransferase (CAT) constructs containing either exon 1A or 1B. Those containing exon 1A were expressed in HeLa cells, whereas the erythroid-specific construct containing exon 1B was not. In contrast, the housekeeping and erythroid constructs were both expressed in erythroleukemia cells.MAPPING
In linkage studies, Amorim et al. (1982) excluded linkage of the ALAD gene with MNSs, Fy, Jk, Rh, HLA, ACP1, and PGM1. Close linkage (theta 0.05 or less) was also excluded for K, PI, GPT, PGP, PGM3, GLO, and BF. Haptoglobin showed a lod score of 0.922 at theta of 0.20 or less. Eiberg et al. (1983) demonstrated linkage of ALAD to the ABO-AK1-ORM linkage group on chromosome 9q. The most likely sequence was judged to be ABO-AK1-ALADH-ORM. The lod and recombination values were as follows: ABO-AK1 (6.27, 0.13); ABO-ALADH (5.38, 0.21); ABO-ORM (5.06, 0.27); AK1-ORM (1.63, 0.17); ALADH-ORM (7.05, 0.13) and AK1-ALADH (2.45, 0.11). Amorim et al. (1984) presented data supporting the chromosome 9 assignment in man. Beaumont et al. (1984) assigned ALAD to chromosome 9 by somatic cell hybrid studies. They used two enzyme assays: one specific for the human enzyme and one indicative of both rodent and human enzymes. The ratio of the values was used to discriminate between positive and negative clones. Wang et al. (1984) assigned the ALAD gene to 9q by study of human-mouse somatic cell hybrids with methods that specifically distinguished the mouse and human enzymes. Potluri et al. (1987) localized ALAD to 9q34 by in situ hybridization using a radio-iodine-labeled human ALAD cDNA. In connection with a pulsed field gel electrophoresis analysis of the 9q32-q34 region, which contains a gene for tuberous sclerosis-1 (191100), Harris et al. (1993) found that the ALAD locus was the most proximal of the genes they studied. ALADH is linked to ACO1 (100880) and GALT (606999) in the mouse (Nadeau and Eicher, 1982). ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 125270 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed