Annexin A2

Details

Name
Annexin A2
Kind
protein
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
UniProtKB Entry
P07355Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
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
cadherin binding involved in cell-cell adhesion / cytoskeletal protein binding / identical protein binding / phosphatidylserine binding / RNA binding / serine-type endopeptidase inhibitor activity
Processes
cell-matrix adhesion / epithelial cell apoptotic process / lung development / mRNA transcription by RNA polymerase II / positive regulation of exocytosis / 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 plasma membrane repair / positive regulation of plasminogen activation / positive regulation of receptor recycling / positive regulation of receptor-mediated endocytosis involved in cholesterol transport / positive regulation of transcription by RNA polymerase II / positive regulation of vacuole organization / regulation of neurogenesis / response to activity / vesicle budding from membrane
Components
adherens junction / AnxA2-p11 complex / azurophil granule lumen / collagen-containing extracellular matrix / cornified envelope / cytoplasm / extracellular region / lipid droplet / nuclear matrix / plasma membrane protein complex / RNA polymerase II transcription regulator complex / vesicle membrane
General 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)
Specific Function
cadherin binding involved in cell-cell adhesion
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
Not Available
Cellular Location
Secreted, extracellular space, extracellular matrix, basement membrane
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
15q22.2
External Identifiers
ResourceLink
UniProtKB IDP07355
UniProtKB Entry NameANXA2_HUMAN
GenBank Protein ID219910
GenBank Gene IDD00017
GeneCard IDANXA2
GenAtlas IDANXA2
HGNC IDHGNC:537
PDB ID(s)1W7B, 1XJL, 2HYU, 2HYV, 2HYW, 4DRW, 4FTG, 4HRH, 5LPU, 5LPX, 5LQ0, 5LQ2, 5N7D, 5N7F, 5N7G, 6TWQ, 6TWU, 6TWX, 6TWY, 7DTO, 7EQ7, 7NMI, 7P70, 7P71, 7P72, 7P73, 7P74, 7PC3, 7PC4, 7PC5, 7PC7, 7PC8, 7PC9, 7PCB, 7QQL, 7QQM, 7QQN, 7ZVN, 7ZVX, 8AEL
KEGG IDhsa:302
NCBI Gene ID302
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]

Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
TenecteplaseapprovedunknowntargetDetails
LanoteplaseinvestigationalunknowntargetDetails
Artenimolapproved, experimental, investigationalunknowntargetligandDetails
Fluocinolone acetonideapproved, investigational, vet_approvedyestargetinducerDetails