Annexin A5 (ANXA5)
The protein contains 320 amino acids for an estimated molecular weight of 35937 Da.
This protein is an anticoagulant protein that acts as an indirect inhibitor of the thromboplastin-specific complex, which is involved in the blood coagulation cascade. (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.
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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Biological Process
Blood coagulation
Cellular response to gonadotropin-releasing hormone
Cellular response to lead ion
Negative regulation of apoptotic process
Negative regulation of blood coagulation
Negative regulation of catalytic activity
Negative regulation of coagulation
Negative regulation of prolactin secretion
Negative regulation of sequestering of calcium ion
Platelet degranulation
Positive regulation of apoptotic process
Protein homooligomerization
Regulation of flagellated sperm motility
Response to calcium ion
Response to organic substance
Response to thyroid hormone
Signal transduction
The reference OMIM entry for this protein is 131230
Annexin a5; anxa5
Annexin v; anx5
Endonexin ii; enx2
Placental anticoagulant protein i
Vascular anticoagulant-alpha
Lipocortin v
Placental protein 4; pp4
Anchorin cii
CLONING
PP4 is an anticoagulant protein that acts as an indirect inhibitor of the thromboplastin-specific complex, which is involved in the blood coagulation cascade. It has a relative molecular weight of about 35,000 and is present in placental tissue to the extent of about 50 mg per placenta with very little secretion into the maternal bloodstream. The PP4 cDNA encoded a protein of 320 amino acid residues. In addition to the PP4 cDNA, Grundmann et al. (1988) identified cDNA encoding a protein with 74% identity to PP4, which they termed PP4-X. PP4 and PP4-X belong to the lipocortin family, as judged by their homology to lipocortin I (151690) and calpactin I (114085). The placental anticoagulant protein called PAP, isolated by Funakoshi et al. (1987), may be the same protein. PP4 is also known as endonexin II. Endonexin II is a member of the family of Ca(2+)-dependent phospholipid binding proteins, known as annexins, which bind to the phospholipids that are preferentially located on the cytosolic face of the plasma membrane. Kaplan et al. (1988) cloned endonexin II cDNA and expressed it in Escherichia coli. A single mRNA, approximately 1.6 kb long, was found to be expressed in human cell lines and placenta. The length of the cDNA clone was 1.59 kb. The cDNA predicted a 320-amino acid protein with a sequence in agreement with the previously determined partial amino acid sequence of endonexin II isolated from placenta.MAPPING
Using a cDNA clone of endonexin II, Modi et al. (1989) assigned the ANXA5 gene to 4q28-q31 by in situ hybridization and Southern analysis of human-rodent cell hybrid DNAs. Tait et al. (1991) found a somewhat different localization which overlapped with the assignment of Modi et al. (1989). By in situ hybridization with a cDNA probe and by polymerase chain reaction (PCR) analysis of a human/hamster hybrid cell panel, they assigned the ANXA5 gene to 4q26-q28. The regional localization was supported by Southern blot analysis of a human cell line with a deletion in 4q23-q27. A compromise assignment might be 4q26-q28. Rodriguez-Garcia et al. (1996) mapped the homologous gene to mouse chromosome 3.GENE FUNCTION
Annexin V forms the voltage-dependent Ca(2+) channels in phospholipid bilayers and was the first ion channel to be structurally and functionally characterized. Demange et al. (1994) outlined data indicating that key amino acid residues act as selectivity filters and voltage sensors, thereby regulating the permeability of the channel pore to ions. Tzima et al. (2000) showed that annexin V bound to F-actin and gamma-actin (ACTG1; 102560), but not beta-actin (ACTB; 102630), in activated human platelets.MOLECULAR GENETICS
In 70 German patients with recurrent pregnancy loss (RPRGL3; 614391) who were known to carry neither factor V Leiden (612309.0001) nor a prothrombin (176930) mutation, Bogdanova et al. (2007) analyzed the ANXA5 gene and identified 4 consecutive nucleotide substitutions in the promoter region that were transmitted as a joint haplotype designated 'M2' (131230.0001). Carriers of the M2 haplotype had a 2- to 4-fold higher risk of RPRGL than noncarriers.ANIMAL MODEL
Brachvogel et al. (2003) found that heterozygous and homozygous Anxa5-deficient mice were born at expected mendelian ratios, were viable and fertile, and showed no obvious phenotypic or behavioral abnormalities. ... 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 131230 was added.
Jan. 27, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed