Porphobilinogen deaminase (HMBS)
The protein contains 361 amino acids for an estimated molecular weight of 39330 Da.
Tetrapolymerization of the monopyrrole PBG into the hydroxymethylbilane pre-uroporphyrinogen in several discrete steps. (updated: March 4, 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.
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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The reference OMIM entry for this protein is 176000
Porphyria, acute intermittent; aip
Porphyria, swedish type
Porphobilinogen deaminase deficiency
Pbgd deficiency
Uroporphyrinogen synthase deficiency
Ups deficiency porphyria, acute intermittent, nonerythroid variant, included
Porphyria, c
A number sign (#) is used with this entry because acute intermittent porphyria (AIP) is caused by heterozygous mutation in the gene encoding hydroxymethylbilane synthase (HMBS; 609806), also referred to as porphobilinogen deaminase (PBGD), on chromosome 11q23.
DESCRIPTION
Porphyrias are inherited defects in the biosynthesis of heme. Acute intermittent porphyria, the most common form of porphyria, is an autosomal dominant disorder characterized by recurrent attacks of abdominal pain, gastrointestinal dysfunction, and neurologic disturbances. In the classic form of AIP, both the ubiquitous 'nonerythroid' housekeeping HMBS isoform and the 'erythroid' HMBS isoform are deficient. However, about 5% of families have the 'nonerythroid variant' of AIP, with a defect only in the ubiquitous nonerythroid HMBS isoform and normal levels of the erythroid HMBS isoform. Clinical characteristics in the 2 forms are identical; diagnostic methods based on the level of enzyme in erythrocytes is ineffective (Puy et al., 1998; Petrides, 1998; Whatley et al., 2000). There are several other forms of porphyria: see porphyria cutanea tarda (176100), variegata porphyria (176200), coproporphyria (121300), acute hepatic porphyria (125270), and congenital erythropoietic porphyria (263700).CLINICAL FEATURES
Acute intermittent porphyria is characterized clinically by acute episodes of a variety of gastrointestinal and neuropathic symptoms; between episodes, the patient is healthy. Abdominal pain is the most common symptom, sometimes with constipation and urinary retention; paraesthesias and paralysis also occur, and death may result from respiratory paralysis (Goldberg, 1959; Stein and Tschudy, 1970; Becker and Kramer, 1977). Many other phenomena, including seizures, psychotic episodes, and hypertension, may occur in acute attacks. Acute attacks rarely occur before puberty; they may be precipitated by porphyrinogenic drugs such as barbiturates and sulfonamides (for list, see Tschudy et al., 1975), some of which are known to induce the earlier rate-controlling step in heme synthesis, delta-aminolevulinic acid (ALA) synthesis. Other known precipitants are alcohol, infection, starvation, and hormonal changes; attacks are more common in women. Only about 10 to 20% of AIP gene carriers become symptomatic during their lifetime (Petrides, 1998). From a survey of AIP cases in the west of Scotland, Yeung Laiwah et al. (1983) observed an association with early-onset chronic renal failure. Porphyria-induced hypertension was considered the most likely causal factor, but enhanced susceptibility to analgesic nephropathy and nephrotoxic effects of porphyrins and their precursors were mentioned as possibilities. Beukeveld et al. (1990) reported a rare case of a child with presumed homozygous AIP who demonstrated porencephaly and severe developmental retardation. The child consistently excreted excessive amounts of delta-aminolevulinic acid, porphobilinogen, and uroporphyrin in her urine from early childhood. She died at age 8 years. Her mother suffered from AIP. Although the father never had attacks, blood and urine studies showed that he too was affected. Using allele-specific oligonucleotides, Picat et al. (1990) demonstrated that the proband reported by Beukeveld et al. (1990) was compound heterozygous for 2 mutations in the HMBS gene (609806.0005; 609806.0006). Each parent was heterozygous for 1 of the mutations. Hessels et al. (2004) described a 7-year-old b ... 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 176000 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed