Annexin A1

Details

Name
Annexin A1
Synonyms
  • Annexin I
  • Annexin-1
  • ANX1
  • Calpactin II
  • Calpactin-2
  • Chromobindin-9
  • Lipocortin I
  • LPC1
  • p35
  • Phospholipase A2 inhibitory protein
Gene Name
ANXA1
UniProtKB Entry
P04083Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0010292|Annexin A1
MAMVSEFLKQAWFIENEEQEYVQTVKSSKGGPGSAVSPYPTFNPSSDVAALHKAIMVKGV
DEATIIDILTKRNNAQRQQIKAAYLQETGKPLDETLKKALTGHLEEVVLALLKTPAQFDA
DELRAAMKGLGTDEDTLIEILASRTNKEIRDINRVYREELKRDLAKDITSDTSGDFRNAL
LSLAKGDRSEDFGVNEDLADSDARALYEAGERRKGTDVNVFNTILTTRSYPQLRRVFQKY
TKYSKHDMNKVLDLELKGDIEKCLTAIVKCATSKPAFFAEKLHQAMKGVGTRHKALIRIM
VSRSEIDMNDIKAFYQKMYGISLCQAILDETKGDYEKILVALCGGN
Number of residues
346
Molecular Weight
38713.855
Theoretical pI
7.04
GO Classification
Functions
cadherin binding involved in cell-cell adhesion / lipid binding / phosphatidylserine binding / signaling receptor binding
Processes
actin cytoskeleton organization / cellular response to vascular endothelial growth factor stimulus / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / negative regulation of interleukin-8 production / neutrophil activation / positive regulation of cell migration involved in sprouting angiogenesis
Components
adherens junction / collagen-containing extracellular matrix / cytosol / vesicle membrane
General Function
Plays important roles in the innate immune response as effector of glucocorticoid-mediated responses and regulator of the inflammatory process. Has anti-inflammatory activity (PubMed:8425544). Plays a role in glucocorticoid-mediated down-regulation of the early phase of the inflammatory response (By similarity). Contributes to the adaptive immune response by enhancing signaling cascades that are triggered by T-cell activation, regulates differentiation and proliferation of activated T-cells (PubMed:17008549). Promotes the differentiation of T-cells into Th1 cells and negatively regulates differentiation into Th2 cells (PubMed:17008549). Has no effect on unstimulated T cells (PubMed:17008549). Negatively regulates hormone exocytosis via activation of the formyl peptide receptors and reorganization of the actin cytoskeleton (PubMed:19625660). Has high affinity for Ca(2+) and can bind up to eight Ca(2+) ions (By similarity). Displays Ca(2+)-dependent binding to phospholipid membranes (PubMed:2532504, PubMed:8557678). Plays a role in the formation of phagocytic cups and phagosomes. Plays a role in phagocytosis by mediating the Ca(2+)-dependent interaction between phagosomes and the actin cytoskeleton (By similarity)
Specific Function
Cadherin binding involved in cell-cell adhesion
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
Not Available
Cellular Location
Nucleus
Gene sequence
>lcl|BSEQ0010293|Annexin A1 (ANXA1)
ATGGCAATGGTATCAGAATTCCTCAAGCAGGCCTGGTTTATTGAAAATGAAGAGCAGGAA
TATGTTCAAACTGTGAAGTCATCCAAAGGTGGTCCCGGATCAGCGGTGAGCCCCTATCCT
ACCTTCAATCCATCCTCGGATGTCGCTGCCTTGCATAAGGCCATAATGGTTAAAGGTGTG
GATGAAGCAACCATCATTGACATTCTAACTAAGCGAAACAATGCACAGCGTCAACAGATC
AAAGCAGCATATCTCCAGGAAACAGGAAAGCCCCTGGATGAAACACTGAAGAAAGCCCTT
ACAGGTCACCTTGAGGAGGTTGTTTTAGCTCTGCTAAAAACTCCAGCGCAATTTGATGCT
GATGAACTTCGTGCTGCCATGAAGGGCCTTGGAACTGATGAAGATACTCTAATTGAGATT
TTGGCATCAAGAACTAACAAAGAAATCAGAGACATTAACAGGGTCTACAGAGAGGAACTG
AAGAGAGATCTGGCCAAAGACATAACCTCAGACACATCTGGAGATTTTCGGAACGCTTTG
CTTTCTCTTGCTAAGGGTGACCGATCTGAGGACTTTGGTGTGAATGAAGACTTGGCTGAT
TCAGATGCCAGGGCCTTGTATGAAGCAGGAGAAAGGAGAAAGGGGACAGACGTAAACGTG
TTCAATACCATCCTTACCACCAGAAGCTATCCACAACTTCGCAGAGTGTTTCAGAAATAC
ACCAAGTACAGTAAGCATGACATGAACAAAGTTCTGGACCTGGAGTTGAAAGGTGACATT
GAGAAATGCCTCACAGCTATCGTGAAGTGCGCCACAAGCAAACCAGCTTTCTTTGCAGAG
AAGCTTCATCAAGCCATGAAAGGTGTTGGAACTCGCCATAAGGCATTGATCAGGATTATG
GTTTCCCGTTCTGAAATTGACATGAATGATATCAAAGCATTCTATCAGAAGATGTATGGT
ATCTCCCTTTGCCAAGCCATCCTGGATGAAACCAAAGGAGATTATGAGAAAATCCTGGTG
GCTCTTTGTGGAGGAAACTAA
Chromosome Location
9
Locus
9q21.13
External Identifiers
ResourceLink
UniProtKB IDP04083
UniProtKB Entry NameANXA1_HUMAN
GenBank Protein ID12654863
GenBank Gene IDBC001275
GeneCard IDANXA1
GenAtlas IDANXA1
HGNC IDHGNC:533
PDB ID(s)1AIN, 1BO9, 1QLS, 5VFW
KEGG IDhsa:301
NCBI Gene ID301
General References
  1. Wallner BP, Mattaliano RJ, Hession C, Cate RL, Tizard R, Sinclair LK, Foeller C, Chow EP, Browing JL, Ramachandran KL, et al.: Cloning and expression of human lipocortin, a phospholipase A2 inhibitor with potential anti-inflammatory activity. Nature. 1986 Mar 6-12;320(6057):77-81. [Article]
  2. Kovacic RT, Tizard R, Cate RL, Frey AZ, Wallner BP: Correlation of gene and protein structure of rat and human lipocortin I. Biochemistry. 1991 Sep 17;30(37):9015-21. [Article]
  3. Arcone R, Arpaia G, Ruoppolo M, Malorni A, Pucci P, Marino G, Ialenti A, Di Rosa M, Ciliberto G: Structural characterization of a biologically active human lipocortin 1 expressed in Escherichia coli. Eur J Biochem. 1993 Jan 15;211(1-2):347-55. [Article]
  4. 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]
  5. Varticovski L, Chahwala SB, Whitman M, Cantley L, Schindler D, Chow EP, Sinclair LK, Pepinsky RB: Location of sites in human lipocortin I that are phosphorylated by protein tyrosine kinases and protein kinases A and C. Biochemistry. 1988 May 17;27(10):3682-90. [Article]
  6. Biemann K, Scoble HA: Characterization by tandem mass spectrometry of structural modifications in proteins. Science. 1987 Aug 28;237(4818):992-8. [Article]
  7. Pepinsky RB, Sinclair LK, Chow EP, O'Brine-Greco B: A dimeric form of lipocortin-1 in human placenta. Biochem J. 1989 Oct 1;263(1):97-103. [Article]
  8. Mailliard WS, Haigler HT, Schlaepfer DD: Calcium-dependent binding of S100C to the N-terminal domain of annexin I. J Biol Chem. 1996 Jan 12;271(2):719-25. [Article]
  9. Perretti M, Christian H, Wheller SK, Aiello I, Mugridge KG, Morris JF, Flower RJ, Goulding NJ: Annexin I is stored within gelatinase granules of human neutrophil and mobilized on the cell surface upon adhesion but not phagocytosis. Cell Biol Int. 2000;24(3):163-74. [Article]
  10. Dorovkov MV, Ryazanov AG: Phosphorylation of annexin I by TRPM7 channel-kinase. J Biol Chem. 2004 Dec 3;279(49):50643-6. Epub 2004 Oct 12. [Article]
  11. Ernst S, Lange C, Wilbers A, Goebeler V, Gerke V, Rescher U: An annexin 1 N-terminal peptide activates leukocytes by triggering different members of the formyl peptide receptor family. J Immunol. 2004 Jun 15;172(12):7669-76. [Article]
  12. D'Acquisto F, Merghani A, Lecona E, Rosignoli G, Raza K, Buckley CD, Flower RJ, Perretti M: Annexin-1 modulates T-cell activation and differentiation. Blood. 2007 Feb 1;109(3):1095-102. Epub 2006 Sep 28. [Article]
  13. D'Acquisto F, Perretti M, Flower RJ: Annexin-A1: a pivotal regulator of the innate and adaptive immune systems. Br J Pharmacol. 2008 Sep;155(2):152-69. doi: 10.1038/bjp.2008.252. Epub 2008 Jul 21. [Article]
  14. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [Article]
  15. McArthur S, Yazid S, Christian H, Sirha R, Flower R, Buckingham J, Solito E: Annexin A1 regulates hormone exocytosis through a mechanism involving actin reorganization. FASEB J. 2009 Nov;23(11):4000-10. doi: 10.1096/fj.09-131391. Epub 2009 Jul 22. [Article]
  16. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [Article]
  17. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. [Article]
  18. 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]
  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. Leoni G, Neumann PA, Kamaly N, Quiros M, Nishio H, Jones HR, Sumagin R, Hilgarth RS, Alam A, Fredman G, Argyris I, Rijcken E, Kusters D, Reutelingsperger C, Perretti M, Parkos CA, Farokhzad OC, Neish AS, Nusrat A: Annexin A1-containing extracellular vesicles and polymeric nanoparticles promote epithelial wound repair. J Clin Invest. 2015 Mar 2;125(3):1215-27. doi: 10.1172/JCI76693. Epub 2015 Feb 9. [Article]
  21. Weng X, Luecke H, Song IS, Kang DS, Kim SH, Huber R: Crystal structure of human annexin I at 2.5 A resolution. Protein Sci. 1993 Mar;2(3):448-58. [Article]
  22. Gao J, Li Y, Yan H: NMR solution structure of domain 1 of human annexin I shows an autonomous folding unit. J Biol Chem. 1999 Jan 29;274(5):2971-7. [Article]
  23. Rety S, Osterloh D, Arie JP, Tabaries S, Seeman J, Russo-Marie F, Gerke V, Lewit-Bentley A: Structural basis of the Ca(2+)-dependent association between S100C (S100A11) and its target, the N-terminal part of annexin I. Structure. 2000 Feb 15;8(2):175-84. [Article]

Associated Data

Bio-Entities
Bio-EntityType
Annexin A1 (Humans)protein
primary
Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Hydrocortisoneapproved, vet_approvedyestargetagonistDetails
AmcinonideapprovedunknowntargetagonistDetails
Dexamethasoneapproved, investigational, vet_approvedunknowntargetagonistDetails
Hydrocortisone aceponateexperimental, vet_approvedyestargetDetails
Hydrocortisone acetateapproved, vet_approvedyestargetDetails
Hydrocortisone butyrateapproved, vet_approvedyestargetDetails
Hydrocortisone cypionateapproved, investigational, vet_approvedyestargetDetails
Hydrocortisone phosphateapproved, vet_approvedyestargetDetails
Hydrocortisone probutateapproved, vet_approvedyestargetDetails
Hydrocortisone valerateapproved, vet_approvedyestargetDetails
Fluocinolone acetonideapproved, investigational, vet_approvedyestargetinducerDetails
BudesonideapprovedunknowntargetsubstrateDetails
Methylprednisoloneapproved, vet_approvedunknowntargetagonistDetails
Clobetasol propionateapprovedunknowntargetinducerDetails
Prednisolone phosphateapproved, vet_approvedunknowntargetligandDetails
Betamethasone phosphateapproved, vet_approvedunknowntargetagonistDetails
Dexamethasone acetateapproved, investigational, vet_approvedunknowntargetagonistDetails
Cortisone acetateapproved, investigationalunknowntargetinducerDetails
DifluprednateapprovedyestargetagonistDetails