Annexin A2 (ANXA2)
The protein contains 339 amino acids for an estimated molecular weight of 38604 Da.
Calcium-regulated membrane-binding protein whose affinity for calcium is greatly enhanced by anionic phospholipids. It binds two calcium ions with high affinity. May be involved in heat-stress response. Inhibits PCSK9-enhanced LDLR degradation, probably reduces PCSK9 protein levels via a translational mechanism but also competes with LDLR for binding with PCSK9 (PubMed:18799458, PubMed:24808179, PubMed:22848640). (updated: Jan. 31, 2018)
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.
- 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.
This protein is annotated as membranous in Gene Ontology.
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| Variant | Description |
|---|---|
| Does not affect interaction with PCSK9 |
Biological Process
Angiogenesis
Biomineral tissue development
Body fluid secretion
Catabolism by host of symbiont protein
Collagen fibril organization
Endocardial cell differentiation
Fibrinolysis
Growth plate cartilage development
Interleukin-12-mediated signaling pathway
Membrane raft assembly
Negative regulation by host of symbiont molecular function
Negative regulation of catalytic activity
Negative regulation of formation of structure involved in a symbiotic process
Negative regulation of low-density lipoprotein particle receptor catabolic process
Neutrophil degranulation
Osteoclast development
Positive regulation by host of viral process
Positive regulation of binding
Positive regulation of calcium ion transport
Positive regulation of chondrocyte differentiation
Positive regulation of fibroblast proliferation
Positive regulation of low-density lipoprotein particle clearance
Positive regulation of low-density lipoprotein particle receptor binding
Positive regulation of low-density lipoprotein receptor activity
Positive regulation of protein phosphorylation
Positive regulation of receptor recycling
Positive regulation of receptor-mediated endocytosis involved in cholesterol transport
Positive regulation of vacuole organization
Positive regulation of vesicle fusion
Positive regulation of viral life cycle
Protein heterotetramerization
Protein localization to plasma membrane
Protein targeting to plasma membrane
Regulation of plasminogen activation
Response to thyroid hormone
Vesicle budding from membrane
Viral process
Cellular Component
Adherens junction
AnxA2-p11 complex
Azurophil granule lumen
Basement membrane
Basolateral plasma membrane
Cell cortex
Cell surface
Cell-cell adherens junction
Collagen-containing extracellular matrix
Cytoplasm
Cytosol
Early endosome
Endosome
Extracellular exosome
Extracellular matrix
Extracellular region
Extracellular space
Extrinsic component of plasma membrane
Late endosome membrane
Lipid droplet
Lysosomal membrane
Macropinosome
Melanosome
Membrane
Membrane raft
Midbody
Myelin sheath adaxonal region
Nucleus
PCSK9-AnxA2 complex
Perinuclear region of cytoplasm
Plasma membrane
Protein complex
Ruffle
Sarcolemma
Schmidt-Lanterman incisure
Vesicle
Molecular Function
Bone sialoprotein binding
Cadherin binding involved in cell-cell adhesion
Calcium channel activity
Calcium ion binding
Calcium-dependent phospholipid binding
Calcium-dependent protein binding
Cytoskeletal protein binding
Identical protein binding
Molecular function regulator
Phosphatidylinositol-4,5-bisphosphate binding
Phosphatidylserine binding
Phospholipase A2 inhibitor activity
Poly(A) RNA binding
Protease binding
Rab GTPase binding
RNA binding
S100 protein binding
Serine-type endopeptidase inhibitor activity
Virion binding
Voltage-gated calcium channel activity involved in regulation of cytosolic calcium levels
The reference OMIM entry for this protein is 151740
Annexin a2; anxa2
Annexin ii; anx2
Annexin ii, heavy chain
Lipocortin ii; lpc2; lip2 annexin ii pseudogene 1, included; anx2p1, included
Anx2p2, included
Anx2p3, included
CLONING
Huang et al. (1986) purified 2 phospholipase A2 (603603) inhibitors from placenta, ANXA1 (151690) and ANXA2, which they called lipocortin I and II, respectively. Western blot analysis detected ANXA2 at an apparent molecular mass of 35 kD in placenta and in all human and mammalian cell lines tested. Highest expression was found in epithelial cell lines. By screening placenta and monocytic cell line cDNA libraries using a nucleotide probe based on tryptic fragments, Huang et al. (1986) cloned ANXA2. ANXA2 and ANXA1 share about 50% amino acid homology, with highest homology in the central region, which in ANXA1 is important for phospholipase A2 inhibitory activity. Both proteins have a primary structure built from 4 repeats of a single unit, contain an N-terminal tyrosine phosphorylation site, and lack a signal sequence. Annexin II, a major cellular substrate of the tyrosine kinase encoded by the SRC oncogene (190090), belongs to the annexin family of Ca(2+)-dependent phospholipid- and membrane-binding proteins. By screening a cDNA expression library generated from highly purified human osteoclast-like multinuclear cells (MNC) formed in long-term bone marrow cultures, Takahashi et al. (1994) identified a candidate clone that stimulated MNC formation. Sequence analysis showed that this cDNA encoded annexin II. Further studies yielded results suggesting that ANX2 is an autocrine factor that enhances osteoclast formation and bone resorption, a previously unknown function for this molecule.GENE FUNCTION
Formation of the apical surface and lumen is a fundamental step in epithelial organ development. Martin-Belmonte et al. (2007) showed that Pten (601728) localized to the apical plasma membrane during epithelial morphogenesis to mediate enrichment of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) at this domain during cyst development in a 3-dimensional Madin-Darby canine kidney cell system. Ectopic PtdIns(4,5)P2 at the basolateral surface caused apical proteins to relocalize to the basolateral surface. Anx2 bound PtdIns(4,5)P2 and was recruited to the apical surface. Anx2 bound Cdc42 (116952) and recruited it to the apical surface, and Cdc42 in turn recruited the Par6 (607484)/atypical protein kinase C (aPKC; see 176982) complex to the apical surface. Loss of function of Pten, Anx2, Cdc42, or aPKC prevented normal development of the apical surface and lumen. Martin-Belmonte et al. (2007) concluded that PTEN, PtdIns(4,5)P2, ANX2, CDC42, and aPKC control apical plasma membrane and lumen formation. ANXA2 is a binding partner for p11 (S100A10; 114085). Using mice and mouse cells and constructs, Oh et al. (2013) found that Anxa2 and p11 stabilized each other and engaged in a ternary complex with the chromatin-remodeling factor Smarca3 (HLTF; 603257). Determination of the crystal structure revealed that Anxa2 and p11 formed symmetrical dimers that bound 2 Smarca3 peptides aligned in a head-to-head arrangement. Smarca3 interacted with elements of both Anxa2 and p11. Inclusion of Smarca3 in the complex induced a conformational change in Anxa2-p11 that followed an induced-fit model. Smarca3 bound a B-box element in DNA, and inclusion of Anxa2-p11 increased binding of Smarca3 to an immobilized B-box element. Reporter gene assays in mouse N2A neuroblastoma cells revealed that Anxa2-p11 potentiated transcriptional activation by Smarca3. In cells, interaction of Smarca3 with Anxa2-p11 anchored Smarca3 to the nuclear mat ... More on the omim web site
Feb. 5, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
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 ANXA2
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 151740 was added.
Jan. 27, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed