Annexin A2

Details

Name
Annexin A2
Synonyms
  • Annexin II
  • Annexin-2
  • ANX2
  • ANX2L4
  • CAL1H
  • Calpactin I heavy chain
  • Calpactin-1 heavy chain
  • Chromobindin-8
  • Lipocortin II
  • LPC2D
  • p36
  • PAP-IV
  • Placental anticoagulant protein IV
  • Protein I
Gene Name
ANXA2
Organism
Humans
Amino acid sequence
>lcl|BSEQ0002327|Annexin A2
MSTVHEILCKLSLEGDHSTPPSAYGSVKAYTNFDAERDALNIETAIKTKGVDEVTIVNIL
TNRSNAQRQDIAFAYQRRTKKELASALKSALSGHLETVILGLLKTPAQYDASELKASMKG
LGTDEDSLIEIICSRTNQELQEINRVYKEMYKTDLEKDIISDTSGDFRKLMVALAKGRRA
EDGSVIDYELIDQDARDLYDAGVKRKGTDVPKWISIMTERSVPHLQKVFDRYKSYSPYDM
LESIRKEVKGDLENAFLNLVQCIQNKPLYFADRLYDSMKGKGTRDKVLIRIMVSRSEVDM
LKIRSEFKRKYGKSLYYYIQQDTKGDYQKALLYLCGGDD
Number of residues
339
Molecular Weight
38603.63
Theoretical pI
7.91
GO Classification
Functions
calcium ion binding / calcium-dependent phospholipid binding / calcium-dependent protein binding / phosphatidylinositol-4,5-bisphosphate binding / phospholipase A2 inhibitor activity / poly(A) RNA binding / protease binding / S100 protein binding
Processes
angiogenesis / body fluid secretion / collagen fibril organization / fibrinolysis / membrane budding / membrane raft assembly / negative regulation of catalytic activity / negative regulation of low-density lipoprotein particle receptor catabolic process / negative regulation of receptor binding / negative regulation of receptor internalization / osteoclast development / positive regulation of binding / positive regulation of fibroblast proliferation / positive regulation of protein phosphorylation / positive regulation of receptor activity / positive regulation of vesicle fusion / protein heterotetramerization / protein targeting to plasma membrane
Components
basement membrane / basolateral plasma membrane / cell cortex / cell surface / cytosol / early endosome / endosome / extracellular exosome / extracellular space / extrinsic component of plasma membrane / late endosome membrane / lipid particle / lysosomal membrane / macropinosome / melanosome / membrane / midbody / myelin sheath adaxonal region / nucleus / PCSK9-AnxA2 complex / perinuclear region of cytoplasm / plasma membrane / ruffle / sarcolemma / Schmidt-Lanterman incisure / vesicle
General Function
S100 protein binding
Specific Function
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).
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Secreted
Gene sequence
>lcl|BSEQ0010817|Annexin A2 (ANXA2)
ATGTCTACTGTTCACGAAATCCTGTGCAAGCTCAGCTTGGAGGGTGATCACTCTACACCC
CCAAGTGCATATGGGTCTGTCAAAGCCTATACTAACTTTGATGCTGAGCGGGATGCTTTG
AACATTGAAACAGCCATCAAGACCAAAGGTGTGGATGAGGTCACCATTGTCAACATTTTG
ACCAACCGCAGCAATGCACAGAGACAGGATATTGCCTTCGCCTACCAGAGAAGGACCAAA
AAGGAACTTGCATCAGCACTGAAGTCAGCCTTATCTGGCCACCTGGAGACGGTGATTTTG
GGCCTATTGAAGACACCTGCTCAGTATGACGCTTCTGAGCTAAAAGCTTCCATGAAGGGG
CTGGGAACCGACGAGGACTCTCTCATTGAGATCATCTGCTCCAGAACCAACCAGGAGCTG
CAGGAAATTAACAGAGTCTACAAGGAAATGTACAAGACTGATCTGGAGAAGGACATTATT
TCGGACACATCTGGTGACTTCCGCAAGCTGATGGTTGCCCTGGCAAAGGGTAGAAGAGCA
GAGGATGGCTCTGTCATTGATTATGAACTGATTGACCAAGATGCTCGGGATCTCTATGAC
GCTGGAGTGAAGAGGAAAGGAACTGATGTTCCCAAGTGGATCAGCATCATGACCGAGCGG
AGCGTGCCCCACCTCCAGAAAGTATTTGATAGGTACAAGAGTTACAGCCCTTATGACATG
TTGGAAAGCATCAGGAAAGAGGTTAAAGGAGACCTGGAAAATGCTTTCCTGAACCTGGTT
CAGTGCATTCAGAACAAGCCCCTGTATTTTGCTGATCGGCTGTATGACTCCATGAAGGGC
AAGGGGACGCGAGATAAGGTCCTGATCAGAATCATGGTCTCCCGCAGTGAAGTGGACATG
TTGAAAATTAGGTCTGAATTCAAGAGAAAGTACGGCAAGTCCCTGTACTATTATATCCAG
CAAGACACTAAGGGCGACTACCAGAAAGCGCTGCTGTACCTGTGTGGTGGAGATGACTGA
Chromosome Location
15
Locus
15q21-q22
External Identifiers
ResourceLink
UniProtKB IDP07355
UniProtKB Entry NameANXA2_HUMAN
GenBank Protein ID219910
GenBank Gene IDD00017
GenAtlas IDANXA2
HGNC IDHGNC:537
General References
  1. Huang KS, Wallner BP, Mattaliano RJ, Tizard R, Burne C, Frey A, Hession C, McGray P, Sinclair LK, Chow EP, et al.: Two human 35 kd inhibitors of phospholipase A2 are related to substrates of pp60v-src and of the epidermal growth factor receptor/kinase. Cell. 1986 Jul 18;46(2):191-9. [Article]
  2. Spano F, Raugei G, Palla E, Colella C, Melli M: Characterization of the human lipocortin-2-encoding multigene family: its structure suggests the existence of a short amino acid unit undergoing duplication. Gene. 1990 Nov 15;95(2):243-51. [Article]
  3. Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I: The full-ORF clone resource of the German cDNA Consortium. BMC Genomics. 2007 Oct 31;8:399. [Article]
  4. Zody MC, Garber M, Sharpe T, Young SK, Rowen L, O'Neill K, Whittaker CA, Kamal M, Chang JL, Cuomo CA, Dewar K, FitzGerald MG, Kodira CD, Madan A, Qin S, Yang X, Abbasi N, Abouelleil A, Arachchi HM, Baradarani L, Birditt B, Bloom S, Bloom T, Borowsky ML, Burke J, Butler J, Cook A, DeArellano K, DeCaprio D, Dorris L 3rd, Dors M, Eichler EE, Engels R, Fahey J, Fleetwood P, Friedman C, Gearin G, Hall JL, Hensley G, Johnson E, Jones C, Kamat A, Kaur A, Locke DP, Madan A, Munson G, Jaffe DB, Lui A, Macdonald P, Mauceli E, Naylor JW, Nesbitt R, Nicol R, O'Leary SB, Ratcliffe A, Rounsley S, She X, Sneddon KM, Stewart S, Sougnez C, Stone SM, Topham K, Vincent D, Wang S, Zimmer AR, Birren BW, Hood L, Lander ES, Nusbaum C: Analysis of the DNA sequence and duplication history of human chromosome 15. Nature. 2006 Mar 30;440(7084):671-5. [Article]
  5. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  6. Jindal HK, Chaney WG, Anderson CW, Davis RG, Vishwanatha JK: The protein-tyrosine kinase substrate, calpactin I heavy chain (p36), is part of the primer recognition protein complex that interacts with DNA polymerase alpha. J Biol Chem. 1991 Mar 15;266(8):5169-76. [Article]
  7. Hyatt SL, Liao L, Chapline C, Jaken S: Identification and characterization of alpha-protein kinase C binding proteins in normal and transformed REF52 cells. Biochemistry. 1994 Feb 8;33(5):1223-8. [Article]
  8. Wright JF, Kurosky A, Wasi S: An endothelial cell-surface form of annexin II binds human cytomegalovirus. Biochem Biophys Res Commun. 1994 Feb 15;198(3):983-9. [Article]
  9. Emans N, Gorvel JP, Walter C, Gerke V, Kellner R, Griffiths G, Gruenberg J: Annexin II is a major component of fusogenic endosomal vesicles. J Cell Biol. 1993 Mar;120(6):1357-69. [Article]
  10. Gould KL, Woodgett JR, Isacke CM, Hunter T: The protein-tyrosine kinase substrate p36 is also a substrate for protein kinase C in vitro and in vivo. Mol Cell Biol. 1986 Jul;6(7):2738-44. [Article]
  11. Deora AB, Kreitzer G, Jacovina AT, Hajjar KA: An annexin 2 phosphorylation switch mediates p11-dependent translocation of annexin 2 to the cell surface. J Biol Chem. 2004 Oct 15;279(42):43411-8. Epub 2004 Aug 9. [Article]
  12. Giannakopoulos NV, Luo JK, Papov V, Zou W, Lenschow DJ, Jacobs BS, Borden EC, Li J, Virgin HW, Zhang DE: Proteomic identification of proteins conjugated to ISG15 in mouse and human cells. Biochem Biophys Res Commun. 2005 Oct 21;336(2):496-506. [Article]
  13. Chi A, Valencia JC, Hu ZZ, Watabe H, Yamaguchi H, Mangini NJ, Huang H, Canfield VA, Cheng KC, Yang F, Abe R, Yamagishi S, Shabanowitz J, Hearing VJ, Wu C, Appella E, Hunt DF: Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes. J Proteome Res. 2006 Nov;5(11):3135-44. [Article]
  14. Mayer G, Poirier S, Seidah NG: Annexin A2 is a C-terminal PCSK9-binding protein that regulates endogenous low density lipoprotein receptor levels. J Biol Chem. 2008 Nov 14;283(46):31791-801. doi: 10.1074/jbc.M805971200. Epub 2008 Sep 17. [Article]
  15. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
  16. Goel M, Sienkiewicz AE, Picciani R, Lee RK, Bhattacharya SK: Cochlin induced TREK-1 co-expression and annexin A2 secretion: role in trabecular meshwork cell elongation and motility. PLoS One. 2011;6(8):e23070. doi: 10.1371/journal.pone.0023070. Epub 2011 Aug 23. [Article]
  17. Seidah NG, Poirier S, Denis M, Parker R, Miao B, Mapelli C, Prat A, Wassef H, Davignon J, Hajjar KA, Mayer G: Annexin A2 is a natural extrahepatic inhibitor of the PCSK9-induced LDL receptor degradation. PLoS One. 2012;7(7):e41865. doi: 10.1371/journal.pone.0041865. Epub 2012 Jul 27. [Article]
  18. Ly K, Saavedra YG, Canuel M, Routhier S, Desjardins R, Hamelin J, Mayne J, Lazure C, Seidah NG, Day R: Annexin A2 reduces PCSK9 protein levels via a translational mechanism and interacts with the M1 and M2 domains of PCSK9. J Biol Chem. 2014 Jun 20;289(25):17732-46. doi: 10.1074/jbc.M113.541094. Epub 2014 May 7. [Article]
  19. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
  20. Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. [Article]
  21. Burger A, Berendes R, Liemann S, Benz J, Hofmann A, Gottig P, Huber R, Gerke V, Thiel C, Romisch J, Weber K: The crystal structure and ion channel activity of human annexin II, a peripheral membrane protein. J Mol Biol. 1996 Apr 12;257(4):839-47. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00031TenecteplaseapprovedunknownDetails
DB06245LanoteplaseinvestigationalunknownDetails
DB11638Artenimolapproved, experimental, investigationalunknownligandDetails
DB00591Fluocinolone acetonideapproved, investigational, vet_approvedyesinducerDetails