Alpha-2-HS-glycoprotein (AHSG)
The protein contains 367 amino acids for an estimated molecular weight of 39325 Da.
Promotes endocytosis, possesses opsonic properties and influences the mineral phase of bone. Shows affinity for calcium and barium ions. (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.
- 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.
- 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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| Variant | Description |
|---|---|
| dbSNP:rs7633550 | |
| allele AHSG*1 | |
| allele AHSG*1 | |
| allele AHSG*5 | |
| allele AHSG*3 | |
| APMR1 |
Biological Process
Acute-phase response
Cellular protein metabolic process
Negative regulation of biomineral tissue development
Negative regulation of bone mineralization
Negative regulation of endopeptidase activity
Negative regulation of insulin receptor signaling pathway
Negative regulation of phosphorylation
Neutrophil degranulation
Ossification
Pinocytosis
Platelet degranulation
Positive regulation of phagocytosis
Post-translational protein modification
Regulation of bone mineralization
Regulation of inflammatory response
Skeletal system development
The reference OMIM entry for this protein is 138680
Alpha-2-hs-glycoprotein; ahsg
A2hs; ahs; hsga
Fetuin, mouse, homolog of
Fetuin a; fetua
CLONING
Anderson and Anderson (1977) applied the 2-D electrophoretic technique of O'Farrell (O'Farrell, 1975) to the analysis of human plasma proteins. Genetic variants involving charge or size 'should be routinely detectable in at least 20 proteins at once.' About 30 polypeptides were identified, including alpha-2HS-glycoprotein (alpha-2-Heremans-Schmid glycoprotein). They recognized 3 phenotypes reflecting 2 autosomal, about equally frequent, codominant alleles. Using polyacrylamide gel isoelectric focusing with immunofixation, Umetsu et al. (1984) described a polymorphism of alpha-2-HS-glycoproteins with 3 common phenotypes designated AHS1-1, AHS2-1 and AHS2-2. Cox and Andrews (1983) used silver stain immunofixation to demonstrate 3 codominant alleles. A2HS is one of the few 'negative' acute-phase reactants of human plasma. It promotes endocytosis, has opsonic properties, and, because of its high affinity for calcium, probably plays some role in the metabolism of bone where it is concentrated up to 300-fold relative to other plasma proteins. The concentration of AHSG in bone falls progressively throughout childhood to adult life. A2HS consists of 2 polypeptide chains termed A and B. The amino acid sequence of the longer A chain was determined by Yoshioka et al. (1986) and the amino acid sequence and carbohydrate sequence of the shorter B chain were reported by Gejyo et al. (1983). In search of the human homolog for pp63, a phosphorylated rat hepatic glycoprotein that inhibits insulin receptor tyrosine kinase, Srinivas et al. (1993) isolated a DNA clone from a human liver gamma-gt11 cDNA library. DNA sequence analysis revealed identity with the mRNA product of the AHSG gene; the amino acid sequences of AHSG and pp63 showed 70% identity, including complete conservation of the cysteine residues. Northern blot analysis demonstrated a 1.8-kb mRNA in human liver and a hepatoma cell line. AHSG purified from human serum specifically inhibited insulin-stimulated autophosphorylation of the insulin receptor (INSR; 147670) in vitro and in vivo; ASHG also inhibited insulin-induced tyrosine phosphorylation of insulin receptor substrate-1 (IRS1; 147545) and the association of IRS1 with the p85 subunit of phosphatidylinositol-3 kinase (PIK3R1; 171833) in hepatoma cells. ASHG did not compete with insulin for binding to INSR. Srinivas et al. (1993) concluded that human AHSG functions to regulate insulin action at the insulin receptor tyrosine kinase level. The product of the AHSG gene is commonly referred to as fetuin in species other than the human (Jahnen-Dechent, 1998). Terkelsen et al. (1998) described the distribution of protein and mRNA in embryonic and neonatal rat tissues. The first fetal plasma protein to be described was fetuin, which was purified from fetal and newborn calf serum by Pedersen (1944). Fetuin was subsequently shown to be a very abundant plasma protein in fetal cattle, sheep, pig, and goat, and also to be present in humans and rodents.MAPPING
Eiberg et al. (1984) found linkage of A2HS with pseudocholinesterase-E1 (BCHE; 177400)--maximum male lod = 5.02 at theta = 0.10 and with transferrin (TF; 190000). In their data, TF and BCHE showed peak male lod = 2.21 at theta = 0.24. The only positive lod score with the centromere of chromosome 3, which from evidence skimpy at that time was thought to carry the TF-BCHE linkage group, was with TF--0.47 at theta 0.23. They proposed that the order is cen--TF--BCHE--A2H ... 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 AHSG
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 138680 was added.