Adenosylhomocysteinase (AHCY)
The protein contains 432 amino acids for an estimated molecular weight of 47716 Da.
Adenosylhomocysteine is a competitive inhibitor of S-adenosyl-L-methionine-dependent methyl transferase reactions; therefore adenosylhomocysteinase may play a key role in the control of methylations via regulation of the intracellular concentration of adenosylhomocysteine. (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.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- 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.
Biological Process
Cellular nitrogen compound metabolic process
Chronic inflammatory response to antigenic stimulus
Circadian sleep/wake cycle
Homocysteine biosynthetic process
Methylation
One-carbon metabolic process
Response to hypoxia
Response to nutrient
S-adenosylhomocysteine catabolic process
S-adenosylmethionine cycle
Small molecule metabolic process
Sulfur amino acid metabolic process
Xenobiotic metabolic process
The reference OMIM entry for this protein is 180960
S-adenosylhomocysteine hydrolase; ahcy
Sahh
DESCRIPTION
The AHCY gene encodes S-adenosylhomocysteine hydrolase (EC 3.3.1.1), which catalyzes the hydrolysis of S-adenosylhomocysteine to adenosine and homocysteine (summary by Baric et al., 2004).CLONING
Coulter-Karis and Hershfield (1989) isolated cDNA clones for human AHCY from a placental cDNA library. The deduced 432-amino acid protein has a molecular mass of 47.6 kD with 97% identity to the rat protein.GENE FUNCTION
Baric et al. (2004) noted that S-adenosylhomocysteine hydrolase catalyzes the hydrolysis of S-adenosylhomocysteine to adenosine and homocysteine. In eukaryotes, this is the major route for disposal of the S-adenosylhomocysteine formed as a common product of each of many S-adenosylmethionine-dependent methyltransferases. The reaction is reversible, but under normal conditions the removal of both adenosine and homocysteine is sufficiently rapid to maintain the flux in the direction of hydrolysis. Physiologically, S-adenosylhomocysteine hydrolysis serves not only to sustain the flux of methionine sulfur toward cysteine, but is believed also to play a critical role in the regulation of biologic methylations.EVOLUTION
Hershfield and Francke (1982) noted that in ADA deficiency (see 102700), adenosine and deoxyadenosine accumulate and, respectively, inhibit and inactivate S-adenosylhomocysteine hydrolase. The fact that both SAHH and ADA are on chromosome 20 suggests an evolutionary relationship. SAHH, which is a eukaryotic enzyme, probably arose after ADA, which occurs also in prokaryotes. Evolution of SAHH may have required the simultaneous occurrence of ADA to avoid the adverse effects of adenosine and deoxyadenosine. Alternatively, tandem reduplication of a portion of the ADA gene encoding a binding domain for adenosine may have occurred and further changes may have led to the SAHH gene. SAHH is a major high affinity cytoplasmic adenosine-binding protein.MAPPING
By analysis of human-Chinese hamster hybrids, Hershfield and Francke (1982) assigned the AHCY gene to chromosome 20. By study of rearranged human chromosomes in human-rodent cell hybrids, Mohandas et al. (1984) assigned the SAHH locus to 20cen-q13.1 and the ADA gene (608958) to 20q13.1-qter. Eiberg and Mohr (1985) looked at linkage of ADA and SAHH in their Danish family data; 8 families were informative for polymorphism of these enzymes. The data gave a maximum lod score of 1.59 at theta = 0.15 for males and females combined. In an informative South African family, Bissbort et al. (1987) found a recombination fraction of about 0.18 between SAHH and ADA. Combined with the published findings in Danish families, the recombination fraction for the pooled data was calculated to be 0.4 in men, 0.08 in women, and 0.13 in the sexes taken together.MOLECULAR GENETICS
Bissbort et al. (1983) found that the SAHH gene is polymorphic in southwest Germany with 2 common alleles: SAHH*1 and SAHH*2, with frequencies of 0.96 and 0.04, respectively. In the Japanese population, Akiyama et al. (1984) estimated the gene frequencies of SAHH*1 and SAHH*2 to be 0.953 and 0.047, respectively, similar to the results reported by Bissbort et al. (1983). Data on gene frequencies of allelic variants were tabulated by Roychoudhury and Nei (1988). By starch gel electrophoresis, Arredondo-Vega et al. (1989) identified 2 variant alleles in erythrocyte AHCY. In a British population, the gene frequencies were 0.024 for AHCY*2 and ... 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 25, 2017: Additional information
No protein expression data in P. Mayeux work for AHCY
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 180960 was added.
Jan. 27, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed