Annexin A2

Annexin A2 also known as annexin II is a protein that in humans is encoded by the ANXA2 gene.[5]

ANXA2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1W7B, 1XJL, 2HYU, 2HYV, 2HYW, 4DRW, 4FTG, 4HRH
Identifiers
Aliases	ANXA2, ANX2, ANX2L4, CAL1H, HEL-S-270, LIP2, LPC2, LPC2D, P36, PAP-IV, annexin A2
External IDs	OMIM: 151740 MGI: 88246 HomoloGene: 20857 GeneCards: ANXA2
Gene location (Human) Chr. Chromosome 15 (human)[1] Band 15q22.2 Start 60,347,134 bp[1] End 60,402,883 bp[1]
Gene location (Mouse) Chr. Chromosome 9 (mouse)[2] Band 9 C|9 38.58 cM Start 69,453,620 bp[2] End 69,491,795 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • phospholipase inhibitor activity • calcium ion binding • S100 protein binding • phospholipase A2 inhibitor activity • calcium-dependent protein binding • protease binding • cytoskeletal protein binding • Rab GTPase binding • GO:0001948 protein binding • calcium-dependent phospholipid binding • phosphatidylinositol-4,5-bisphosphate binding • cadherin binding involved in cell-cell adhesion • RNA binding • identical protein binding • bone sialoprotein binding • molecular function regulator • phosphatidylserine binding • calcium channel activity • virion binding • voltage-gated calcium channel activity involved in regulation of cytosolic calcium levels Cellular component • vesicle • cytosol • endosome • membrane • late endosome membrane • melanosome • ruffle • proteinaceous extracellular matrix • cell membrane • lipid droplet • myelin sheath adaxonal region • Schmidt-Lanterman incisure • PCSK9-AnxA2 complex • macropinosome • basement membrane • cell surface • lysosomal membrane • basolateral plasma membrane • cell cortex • midbody • early endosome • perinuclear region of cytoplasm • sarcolemma • extrinsic component of plasma membrane • extracellular exosome • cell nucleus • extracellular • azurophil granule lumen • cytoplasm • membrane raft • extracellular matrix • extracellular region • macromolecular complex • collagen-containing extracellular matrix Biological process • negative regulation of low-density lipoprotein particle receptor catabolic process • positive regulation of protein phosphorylation • protein heterotetramerization • fibrinolysis • body fluid secretion • collagen fibril organization • positive regulation of fibroblast proliferation • response to thyroid hormone • positive regulation of binding • positive regulation of vesicle fusion • membrane raft assembly • angiogenesis • vesicle budding from membrane • osteoclast development • cell-cell adhesion • GO:0048553 negative regulation of catalytic activity • positive regulation of receptor recycling • neutrophil degranulation • 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 receptor-mediated endocytosis involved in cholesterol transport • negative regulation of development of symbiont involved in interaction with host • catabolism by host of symbiont protein • negative regulation by host of symbiont molecular function • positive regulation of vacuole organization • interleukin-12-mediated signaling pathway • protein localization to plasma membrane • growth plate cartilage development • regulation of plasminogen activation • biomineral tissue development • positive regulation of chondrocyte differentiation • positive regulation by host of viral process • regulation of cytosolic calcium ion concentration • positive regulation of calcium ion transport • endocardial cell differentiation • calcium ion transmembrane transport • positive regulation of viral life cycle Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	302	12306
Ensembl	ENSG00000182718	ENSMUSG00000032231
UniProt	P07355	P07356
RefSeq (mRNA)	NM_001002857 NM_001002858 NM_001136015 NM_004039	NM_007585
RefSeq (protein)	NP_001002857 NP_001002858 NP_001129487 NP_004030	NP_031611
Location (UCSC)	Chr 15: 60.35 – 60.4 Mb	Chr 9: 69.45 – 69.49 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Annexin 2 is involved in diverse cellular processes such as cell motility (especially that of the epithelial cells), linkage of membrane-associated protein complexes to the actin cytoskeleton, endocytosis, fibrinolysis, ion channel formation, and cell matrix interactions. It is a calcium-dependent phospholipid-binding protein whose function is to help organize exocytosis of intracellular proteins to the extracellular domain. Annexin II is a pleiotropic protein meaning that its function is dependent on place and time in the body.

Gene

The ANXA2 gene, located at 15q22.2, has three pseudogenes located on chromosomes 4, 9 and 10, respectively. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene.[6]

Function

This protein is a member of the annexin family. Members of this calcium-dependent phospholipid-binding protein family play a role in the regulation of cellular growth and in signal transduction pathways. This protein functions as an autocrine factor which heightens osteoclast formation and bone resorption.[6] Epigenetic regulation of Annexin A2 has been identified as a key determinant of mesenchymal transformation in brain tumors.[7]

Annexin A2 has been proposed to function inside the cell in sorting of endosomes and outside the cell in anticoagulant reactions.

Interactions

Annexin A2 has been shown to interact with Prohibitin,[8] CEACAM1,[9] S100A10,[10][11] PCNA,[12] complement Factor H,[13] and a number of viral factors including the HPV16 minor capsid protein L2.[14][15]

See also

• Annexin

References

1. GRCh38: Ensembl release 89: ENSG00000182718 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000032231 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Takahashi S, Reddy SV, Chirgwin JM, Devlin R, Haipek C, Anderson J, Roodman GD (Nov 1994). "Cloning and identification of annexin II as an autocrine/paracrine factor that increases osteoclast formation and bone resorption". The Journal of Biological Chemistry. 269 (46): 28696–701. PMID 7961821.
6. "Entrez Gene: ANXA2 annexin A2".
7. Kling T, Ferrarese R, Ó hAilín D, Johansson P, Heiland DH, Dai F, Vasilikos I, Weyerbrock A, Jörnsten R, Carro MS, Nelander S (Sep 2016). "Integrative Modeling Reveals Annexin A2-mediated Epigenetic Control of Mesenchymal Glioblastoma". EBioMedicine.
8. Bacher S, Achatz G, Schmitz ML, Lamers MC (Dec 2002). "Prohibitin and prohibitone are contained in high-molecular weight complexes and interact with alpha-actinin and annexin A2". Biochimie. 84 (12): 1207–20. doi:10.1016/S0300-9084(02)00027-5. PMID 12628297.
9. Kirshner J, Schumann D, Shively JE (Dec 2003). "CEACAM1, a cell-cell adhesion molecule, directly associates with annexin II in a three-dimensional model of mammary morphogenesis". The Journal of Biological Chemistry. 278 (50): 50338–45. doi:10.1074/jbc.M309115200. PMID 14522961.
10. Réty S, Sopkova J, Renouard M, Osterloh D, Gerke V, Tabaries S, Russo-Marie F, Lewit-Bentley A (Jan 1999). "The crystal structure of a complex of p11 with the annexin II N-terminal peptide". Nature Structural Biology. 6 (1): 89–95. doi:10.1038/4965. PMID 9886297.
11. He KL, Deora AB, Xiong H, Ling Q, Weksler BB, Niesvizky R, Hajjar KA (Jul 2008). "Endothelial cell annexin A2 regulates polyubiquitination and degradation of its binding partner S100A10/p11". The Journal of Biological Chemistry. 283 (28): 19192–200. doi:10.1074/jbc.M800100200. PMC 2443646. PMID 18434302.
12. Ohta S, Shiomi Y, Sugimoto K, Obuse C, Tsurimoto T (Oct 2002). "A proteomics approach to identify proliferating cell nuclear antigen (PCNA)-binding proteins in human cell lysates. Identification of the human CHL12/RFCs2-5 complex as a novel PCNA-binding protein". The Journal of Biological Chemistry. 277 (43): 40362–7. doi:10.1074/jbc.M206194200. PMID 12171929.
13. Leffler J, Herbert AP, Norström E, Schmidt CQ, Barlow PN, Blom AM, Martin M (Feb 2010). "Annexin-II, DNA, and histones serve as factor H ligands on the surface of apoptotic cells". The Journal of Biological Chemistry. 285 (6): 3766–76. doi:10.1074/jbc.M109.045427. PMC 2823518. PMID 19951950.
14. Woodham AW, Da Silva DM, Skeate JG, Raff AB, Ambroso MR, Brand HE, Isas JM, Langen R, Kast WM (2012). "The S100A10 subunit of the annexin A2 heterotetramer facilitates L2-mediated human papillomavirus infection". PLoS One. 7 (8): e43519. doi:10.1371/journal.pone.0043519. PMC 3425544. PMID 22927980.
15. Woodham AW, Raff AB, Raff LM, Da Silva DM, Yan L, Skeate JG, Wong MK, Lin YG, Kast WM (May 2014). "Inhibition of Langerhans cell maturation by human papillomavirus type 16: a novel role for the annexin A2 heterotetramer in immune suppression". Journal of Immunology. 192 (10): 4748–57. doi:10.4049/jimmunol.1303190. PMC 4019435. PMID 24719459.

Further reading

• Kwon M, MacLeod TJ, Zhang Y, Waisman DM (Jan 2005). "S100A10, annexin A2, and annexin a2 heterotetramer as candidate plasminogen receptors". Frontiers in Bioscience. 10 (1–3): 300–25. doi:10.2741/1529. PMID 15574370.
• Babiychuk EB, Draeger A (Jun 2006). "Regulation of ecto-5'-nucleotidase activity via Ca2+-dependent, annexin 2-mediated membrane rearrangement?". Biochemical Society Transactions. 34 (Pt 3): 374–6. doi:10.1042/BST0340374. PMID 16709165.
• Bohn E, Gerke V, Kresse H, Löffler BM, Kunze H (Jan 1992). "Annexin II inhibits calcium-dependent phospholipase A1 and lysophospholipase but not triacyl glycerol lipase activities of rat liver hepatic lipase". FEBS Letters. 296 (3): 237–40. doi:10.1016/0014-5793(92)80294-Q. PMID 1531641.
• Dawson SJ, White LA (May 1992). "Treatment of Haemophilus aphrophilus endocarditis with ciprofloxacin". The Journal of Infection. 24 (3): 317–20. doi:10.1016/S0163-4453(05)80037-4. PMID 1602151.
• Jindal HK, Chaney WG, Anderson CW, Davis RG, Vishwanatha JK (Mar 1991). "The protein-tyrosine kinase substrate, calpactin I heavy chain (p36), is part of the primer recognition protein complex that interacts with DNA polymerase alpha". The Journal of Biological Chemistry. 266 (8): 5169–76. PMID 1825830.
• Filipek A, Gerke V, Weber K, Kuźnicki J (Feb 1991). "Characterization of the cell-cycle-regulated protein calcyclin from Ehrlich ascites tumor cells. Identification of two binding proteins obtained by Ca2(+)-dependent affinity chromatography". European Journal of Biochemistry / FEBS. 195 (3): 795–800. doi:10.1111/j.1432-1033.1991.tb15768.x. PMID 1999197.
• Becker T, Weber K, Johnsson N (Dec 1990). "Protein-protein recognition via short amphiphilic helices; a mutational analysis of the binding site of annexin II for p11". The EMBO Journal. 9 (13): 4207–13. doi:10.1002/j.1460-2075.1990.tb07868.x. PMC 552202. PMID 2148288.
• Spano F, Raugei G, Palla E, Colella C, Melli M (Nov 1990). "Characterization of the human lipocortin-2-encoding multigene family: its structure suggests the existence of a short amino acid unit undergoing duplication". Gene. 95 (2): 243–51. doi:10.1016/0378-1119(90)90367-Z. PMID 2174397.
• Johnsson N, Johnsson K, Weber K (Aug 1988). "A discontinuous epitope on p36, the major substrate of src tyrosine-protein-kinase, brings the phosphorylation site into the neighbourhood of a consensus sequence for Ca2+/lipid-binding proteins". FEBS Letters. 236 (1): 201–4. doi:10.1016/0014-5793(88)80314-4. PMID 2456953.
• Gould KL, Woodgett JR, Isacke CM, Hunter T (Jul 1986). "The protein-tyrosine kinase substrate p36 is also a substrate for protein kinase C in vitro and in vivo". Molecular and Cellular Biology. 6 (7): 2738–44. doi:10.1128/mcb.6.7.2738. PMC 367834. PMID 2946940.
• Huebner K, Cannizzaro LA, Frey AZ, Hecht BK, Hecht F, Croce CM, Wallner BP (May 1988). "Chromosomal localization of the human genes for lipocortin I and lipocortin II". Oncogene Research. 2 (4): 299–310. PMID 2969496.
• Huang KS, Wallner BP, Mattaliano RJ, Tizard R, Burne C, Frey A, Hession C, McGray P, Sinclair LK, Chow EP (Jul 1986). "Two human 35 kd inhibitors of phospholipase A2 are related to substrates of pp60v-src and of the epidermal growth factor receptor/kinase". Cell. 46 (2): 191–9. doi:10.1016/0092-8674(86)90736-1. PMID 3013422.
• Buday L, Egan SE, Rodriguez Viciana P, Cantrell DA, Downward J (Mar 1994). "A complex of Grb2 adaptor protein, Sos exchange factor, and a 36-kDa membrane-bound tyrosine phosphoprotein is implicated in ras activation in T cells". The Journal of Biological Chemistry. 269 (12): 9019–23. PMID 7510700.
• Chung CY, Erickson HP (Jul 1994). "Cell surface annexin II is a high affinity receptor for the alternatively spliced segment of tenascin-C". The Journal of Cell Biology. 126 (2): 539–48. doi:10.1083/jcb.126.2.539. PMC 2200039. PMID 7518469.
• Kato S, Sekine S, Oh SW, Kim NS, Umezawa Y, Abe N, Yokoyama-Kobayashi M, Aoki T (Dec 1994). "Construction of a human full-length cDNA bank". Gene. 150 (2): 243–50. doi:10.1016/0378-1119(94)90433-2. PMID 7821789.
• Richard I, Broux O, Chiannilkulchai N, Fougerousse F, Allamand V, Bourg N, Brenguier L, Devaud C, Pasturaud P, Roudaut C (Oct 1994). "Regional localization of human chromosome 15 loci". Genomics. 23 (3): 619–27. doi:10.1006/geno.1994.1550. PMID 7851890.
• Takahashi S, Reddy SV, Chirgwin JM, Devlin R, Haipek C, Anderson J, Roodman GD (Nov 1994). "Cloning and identification of annexin II as an autocrine/paracrine factor that increases osteoclast formation and bone resorption". The Journal of Biological Chemistry. 269 (46): 28696–701. PMID 7961821.
• Hyatt SL, Liao L, Chapline C, Jaken S (Feb 1994). "Identification and characterization of alpha-protein kinase C binding proteins in normal and transformed REF52 cells". Biochemistry. 33 (5): 1223–8. doi:10.1021/bi00171a023. PMID 8110754.
• Wright JF, Kurosky A, Wasi S (Feb 1994). "An endothelial cell-surface form of annexin II binds human cytomegalovirus". Biochemical and Biophysical Research Communications. 198 (3): 983–9. doi:10.1006/bbrc.1994.1140. PMID 8117306.
• Maruyama K, Sugano S (Jan 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.

External links

• Annexin+A2 at the US National Library of Medicine Medical Subject Headings (MeSH)
• Human ANXA2 genome location and ANXA2 gene details page in the UCSC Genome Browser.