ID ANXA1_HUMAN Reviewed; 346 AA. AC P04083; DT 01-NOV-1986, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 2. DT 16-MAR-2016, entry version 206. DE RecName: Full=Annexin A1; DE AltName: Full=Annexin I; DE AltName: Full=Annexin-1; DE AltName: Full=Calpactin II; DE AltName: Full=Calpactin-2; DE AltName: Full=Chromobindin-9; DE AltName: Full=Lipocortin I {ECO:0000303|PubMed:1832554}; DE AltName: Full=Phospholipase A2 inhibitory protein; DE AltName: Full=p35; GN Name=ANXA1; Synonyms=ANX1, LPC1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=2936963; DOI=10.1038/320077a0; RA Wallner B.P., Mattaliano R.J., Hession C., Cate R.L., Tizard R., RA Sinclair L.K., Foeller C., Chow E.P., Browning J.L., RA Ramachandran K.L., Pepinsky R.B.; RT "Cloning and expression of human lipocortin, a phospholipase A2 RT inhibitor with potential anti-inflammatory activity."; RL Nature 320:77-81(1986). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=1832554; DOI=10.1021/bi00101a015; RA Kovacic R.T., Tizard R., Cate R.L., Frey A.Z., Wallner B.P.; RT "Correlation of gene and protein structure of rat and human lipocortin RT I."; RL Biochemistry 30:9015-9021(1991). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION. RX PubMed=8425544; DOI=10.1111/j.1432-1033.1993.tb19904.x; RA Arcone R., Arpaia G., Ruoppolo M., Malorni A., Pucci P., Marino G., RA Ialenti A., di Rosa M., Ciliberto G.; RT "Structural characterization of a biologically active human lipocortin RT 1 expressed in Escherichia coli."; RL Eur. J. Biochem. 211:347-355(1993). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Cervix, and Lung; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP PARTIAL PROTEIN SEQUENCE, AND PHOSPHORYLATION AT TYR-21 BY EGFR AND RP SER-27 BY PKC. RX PubMed=2457390; DOI=10.1021/bi00410a024; RA Varticovski L., Chahwala S.B., Whitman M., Cantley L., Schindler D., RA Chow E.P., Sinclair L.K., Pepinsky R.B.; RT "Location of sites in human lipocortin I that are phosphorylated by RT protein tyrosine kinases and protein kinases A and C."; RL Biochemistry 27:3682-3690(1988). RN [6] RP ACETYLATION AT ALA-2, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=3303336; DOI=10.1126/science.3303336; RA Biemann K., Scoble H.A.; RT "Characterization by tandem mass spectrometry of structural RT modifications in proteins."; RL Science 237:992-998(1987). RN [7] RP FUNCTION, DIMERIZATION, SUBUNIT, TISSUE SPECIFICITY, PARTIAL PROTEIN RP SEQUENCE, PHOSPHORYLATION, AND SUBCELLULAR LOCATION. RX PubMed=2532504; RA Pepinsky R.B., Sinclair L.K., Chow E.P., O'Brine-Greco B.; RT "A dimeric form of lipocortin-1 in human placenta."; RL Biochem. J. 263:97-103(1989). RN [8] RP INTERACTION WITH S100A11, FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=8557678; DOI=10.1074/jbc.271.2.719; RA Mailliard W.S., Haigler H.T., Schlaepfer D.D.; RT "Calcium-dependent binding of S100C to the N-terminal domain of RT annexin I."; RL J. Biol. Chem. 271:719-725(1996). RN [9] RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=10772777; DOI=10.1006/cbir.1999.0468; RA Perretti M., Christian H., Wheller S.K., Aiello I., Mugridge K.G., RA Morris J.F., Flower R.J., Goulding N.J.; RT "Annexin I is stored within gelatinase granules of human neutrophil RT and mobilized on the cell surface upon adhesion but not RT phagocytosis."; RL Cell Biol. Int. 24:163-174(2000). RN [10] RP PHOSPHORYLATION AT SER-5 BY TRPM7. RX PubMed=15485879; DOI=10.1074/jbc.C400441200; RA Dorovkov M.V., Ryazanov A.G.; RT "Phosphorylation of annexin I by TRPM7 channel-kinase."; RL J. Biol. Chem. 279:50643-50646(2004). RN [11] RP FUNCTION, AND DOMAIN. RX PubMed=15187149; DOI=10.4049/jimmunol.172.12.7669; RA Ernst S., Lange C., Wilbers A., Goebeler V., Gerke V., Rescher U.; RT "An annexin 1 N-terminal peptide activates leukocytes by triggering RT different members of the formyl peptide receptor family."; RL J. Immunol. 172:7669-7676(2004). RN [12] RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=17008549; DOI=10.1182/blood-2006-05-022798; RA D'Acquisto F., Merghani A., Lecona E., Rosignoli G., Raza K., RA Buckley C.D., Flower R.J., Perretti M.; RT "Annexin-1 modulates T-cell activation and differentiation."; RL Blood 109:1095-1102(2007). RN [13] RP REVIEW. RX PubMed=18641677; DOI=10.1038/bjp.2008.252; RA D'Acquisto F., Perretti M., Flower R.J.; RT "Annexin-A1: a pivotal regulator of the innate and adaptive immune RT systems."; RL Br. J. Pharmacol. 155:152-169(2008). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [15] RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF SER-27; SER-34 AND RP SER-45. RX PubMed=19625660; DOI=10.1096/fj.09-131391; RA McArthur S., Yazid S., Christian H., Sirha R., Flower R., RA Buckingham J., Solito E.; RT "Annexin A1 regulates hormone exocytosis through a mechanism involving RT actin reorganization."; RL FASEB J. 23:4000-4010(2009). RN [16] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-239 AND LYS-312, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., RA Walther T.C., Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., RA Mann M.; RT "Quantitative phosphoproteomics reveals widespread full RT phosphorylation site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-34, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [20] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-214, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25772364; DOI=10.1016/j.celrep.2015.02.033; RA Hendriks I.A., Treffers L.W., Verlaan-de Vries M., Olsen J.V., RA Vertegaal A.C.; RT "SUMO-2 orchestrates chromatin modifiers in response to DNA damage."; RL Cell Rep. 10:1778-1791(2015). RN [21] RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DOMAIN. RX PubMed=25664854; DOI=10.1172/JCI76693; RA Leoni G., Neumann P.A., Kamaly N., Quiros M., Nishio H., Jones H.R., RA Sumagin R., Hilgarth R.S., Alam A., Fredman G., Argyris I., RA Rijcken E., Kusters D., Reutelingsperger C., Perretti M., Parkos C.A., RA Farokhzad O.C., Neish A.S., Nusrat A.; RT "Annexin A1-containing extracellular vesicles and polymeric RT nanoparticles promote epithelial wound repair."; RL J. Clin. Invest. 125:1215-1227(2015). RN [22] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH CALCIUM IONS, RP AND CALCIUM-BINDING. RX PubMed=8453382; DOI=10.1002/pro.5560020317; RA Weng X., Luecke H., Song I.S., Kang D.S., Kim S.-H., Huber R.; RT "Crystal structure of human annexin I at 2.5-A resolution."; RL Protein Sci. 2:448-458(1993). RN [23] RP STRUCTURE BY NMR OF 41-113. RX PubMed=9915835; DOI=10.1074/jbc.274.5.2971; RA Gao J., Li Y., Yan H.; RT "NMR solution structure of domain 1 of human annexin I shows an RT autonomous folding unit."; RL J. Biol. Chem. 274:2971-2977(1999). RN [24] RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 2-12 IN COMPLEX WITH RP S100A11, AND INTERACTION WITH S100A11. RX PubMed=10673436; DOI=10.1016/S0969-2126(00)00093-9; RA Rety S., Osterloh D., Arie J.-P., Tabaries S., Seeman J., RA Russo-Marie F., Gerke V., Lewit-Bentley A.; RT "Structural basis of the Ca(2+)-dependent association between S100C RT (S100A11) and its target, the N-terminal part of annexin I."; RL Structure 8:175-184(2000). CC -!- FUNCTION: Plays important roles in the innate immune response as CC effector of glucocorticoid-mediated responses and regulator of the CC inflammatory process. Has anti-inflammatory activity CC (PubMed:8425544). Plays a role in glucocorticoid-mediated down- CC regulation of the early phase of the inflammatory response (By CC similarity). Promotes resolution of inflammation and wound healing CC (PubMed:25664854). Functions at least in part by activating the CC formyl peptide receptors and downstream signaling cascades CC (PubMed:15187149, PubMed:25664854). Promotes chemotaxis of CC granulocytes and monocytes via activation of the formyl peptide CC receptors (PubMed:15187149). Contributes to the adaptive immune CC response by enhancing signaling cascades that are triggered by T- CC cell activation, regulates differentiation and proliferation of CC activated T-cells (PubMed:17008549). Promotes the differentiation CC of T-cells into Th1 cells and negatively regulates differentiation CC into Th2 cells (PubMed:17008549). Has no effect on unstimulated T CC cells (PubMed:17008549). Promotes rearrangement of the actin CC cytoskeleton, cell polarization and cell migration CC (PubMed:15187149). Negatively regulates hormone exocytosis via CC activation of the formyl peptide receptors and reorganization of CC the actin cytoskeleton (PubMed:19625660). Has high affinity for CC Ca(2+) and can bind up to eight Ca(2+) ions (By similarity). CC Displays Ca(2+)-dependent binding to phospholipid membranes CC (PubMed:2532504, PubMed:8557678). Plays a role in the formation of CC phagocytic cups and phagosomes. Plays a role in phagocytosis by CC mediating the Ca(2+)-dependent interaction between phagosomes and CC the actin cytoskeleton (By similarity). CC {ECO:0000250|UniProtKB:P10107, ECO:0000250|UniProtKB:P19619, CC ECO:0000269|PubMed:15187149, ECO:0000269|PubMed:17008549, CC ECO:0000269|PubMed:19625660, ECO:0000269|PubMed:2532504, CC ECO:0000269|PubMed:25664854, ECO:0000269|PubMed:2936963, CC ECO:0000269|PubMed:8425544, ECO:0000269|PubMed:8557678}. CC -!- SUBUNIT: Homodimer; non-covalently linked (By similarity). CC Homodimer; linked by transglutamylation (PubMed:2532504). CC Homodimers linked by transglutamylation are observed in placenta, CC but not in other tissues (PubMed:2532504). Interacts with S100A11 CC (PubMed:8557678, PubMed:10673436). Heterotetramer, formed by two CC molecules each of S100A11 and ANXA1 (PubMed:10673436). Interacts CC with DYSF (By similarity). Interacts with EGFR (By similarity). CC {ECO:0000250|UniProtKB:P10107, ECO:0000250|UniProtKB:P19619, CC ECO:0000269|PubMed:10673436, ECO:0000269|PubMed:2532504, CC ECO:0000269|PubMed:8557678}. CC -!- INTERACTION: CC Q9Y6K9:IKBKG; NbExp=6; IntAct=EBI-354007, EBI-81279; CC Q13546:RIPK1; NbExp=5; IntAct=EBI-354007, EBI-358507; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10772777, CC ECO:0000269|PubMed:19625660}. Cytoplasm CC {ECO:0000269|PubMed:10772777, ECO:0000269|PubMed:17008549, CC ECO:0000269|PubMed:19625660}. Cell projection, cilium CC {ECO:0000250|UniProtKB:P46193}. Cell membrane CC {ECO:0000269|PubMed:10772777}. Membrane CC {ECO:0000269|PubMed:17008549, ECO:0000269|PubMed:2532504, CC ECO:0000269|PubMed:8557678}; Peripheral membrane protein CC {ECO:0000269|PubMed:2532504, ECO:0000269|PubMed:8557678}. Endosome CC membrane {ECO:0000250|UniProtKB:P07150}; Peripheral membrane CC protein {ECO:0000250|UniProtKB:P07150}. Basolateral cell membrane CC {ECO:0000250|UniProtKB:P51662}. Apical cell membrane CC {ECO:0000250|UniProtKB:P10107}. Lateral cell membrane CC {ECO:0000250|UniProtKB:P10107}. Secreted CC {ECO:0000269|PubMed:17008549, ECO:0000269|PubMed:19625660, CC ECO:0000269|PubMed:25664854}. Secreted, extracellular space CC {ECO:0000269|PubMed:25664854}. Cell membrane CC {ECO:0000269|PubMed:10772777, ECO:0000269|PubMed:19625660, CC ECO:0000269|PubMed:25664854}; Peripheral membrane protein CC {ECO:0000269|PubMed:10772777, ECO:0000269|PubMed:19625660, CC ECO:0000269|PubMed:25664854}; Extracellular side CC {ECO:0000269|PubMed:10772777, ECO:0000269|PubMed:19625660, CC ECO:0000269|PubMed:25664854}. Secreted, exosome CC {ECO:0000269|PubMed:25664854}. Cytoplasmic vesicle, secretory CC vesicle lumen {ECO:0000269|PubMed:10772777}. Cell projection, CC phagocytic cup {ECO:0000250|UniProtKB:P10107}. Early endosome CC {ECO:0000250|UniProtKB:P19619}. Cytoplasmic vesicle membrane CC {ECO:0000250|UniProtKB:P19619}; Peripheral membrane protein CC {ECO:0000250|UniProtKB:P19619}. Note=Secreted, at least in part CC via exosomes and other secretory vesicles. Detected in exosomes CC and other extracellular vesicles (PubMed:25664854). Detected in CC gelatinase granules in resting neutrophils (PubMed:10772777). CC Secretion is increased in response to wounding and inflammation CC (PubMed:25664854). Secretion is increased upon T-cell activation CC (PubMed:17008549). Neutrophil adhesion to endothelial cells CC stimulates secretion via gelatinase granules, but foreign particle CC phagocytosis has no effect (PubMed:10772777). Colocalizes with CC actin fibers at phagocytic cups (By similarity). Displays calcium- CC dependent binding to phospholipid membranes (PubMed:2532504, CC PubMed:8557678). {ECO:0000250|UniProtKB:P10107, CC ECO:0000269|PubMed:10772777, ECO:0000269|PubMed:17008549, CC ECO:0000269|PubMed:2532504, ECO:0000269|PubMed:25664854, CC ECO:0000269|PubMed:8557678}. CC -!- TISSUE SPECIFICITY: Detected in resting neutrophils CC (PubMed:10772777). Detected in peripheral blood T-cells CC (PubMed:17008549). Detected in extracellular vesicles in blood CC serum from patients with inflammatory bowel disease, but not in CC serum from healthy donors (PubMed:25664854). Detected in placenta CC (at protein level) (PubMed:2532504). Detected in liver. CC {ECO:0000269|PubMed:2532504, ECO:0000269|PubMed:2936963}. CC -!- DOMAIN: The full-length protein can bind eight Ca(2+) ions via the CC annexin repeats. Calcium binding causes a major conformation CC change that modifies dimer contacts and leads to surface exposure CC of the N-terminal phosphorylation sites; in the absence of Ca(2+), CC these sites are buried in the interior of the protein core. The N- CC terminal region becomes disordered in response to calcium-binding. CC {ECO:0000250|UniProtKB:P19619}. CC -!- DOMAIN: The N-terminal 26 amino acids are sufficient for its CC extracellular functions in the regulation of inflammation and CC wound healing (PubMed:25664854). Acylated peptides that contain CC the first 26 amino acids of the mature protein can activate CC signaling via the formyl peptide receptors (PubMed:15187149, CC PubMed:25664854). {ECO:0000269|PubMed:15187149, CC ECO:0000269|PubMed:25664854}. CC -!- PTM: Phosphorylated by protein kinase C, EGFR and TRPM7 CC (PubMed:2457390, PubMed:15485879). Phosphorylated in response to CC EGF treatment (PubMed:2532504). {ECO:0000269|PubMed:15485879, CC ECO:0000269|PubMed:2457390, ECO:0000269|PubMed:2532504}. CC -!- PTM: Sumoylated. {ECO:0000250|UniProtKB:P10107}. CC -!- PHARMACEUTICAL: Peptides based on the N-terminal sequence might be CC used for the treatment of inflammation, e.g. in chronic bowel CC diseases and in rheumatoid arthritis. {ECO:0000305}. CC -!- MISCELLANEOUS: Was originally identified as calcium and CC phospholipid binding protein that displays Ca(2+)-dependent CC binding to phospholipid membranes and can promote membrane CC aggregation in vitro. Was initially identified as inhibitor of CC phospholipase A2 activity (in vitro) (PubMed:2936963, CC PubMed:8425544). Inhibition of phospholipase activity is mediated CC via its phospholipid binding activity that limits the access of CC phospholipase to its substrates. {ECO:0000269|PubMed:2936963, CC ECO:0000269|PubMed:8425544, ECO:0000305}. CC -!- SIMILARITY: Belongs to the annexin family. {ECO:0000305}. CC -!- SIMILARITY: Contains 4 annexin repeats. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/ANXA1ID653ch9q21.html"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X05908; CAA29338.1; -; mRNA. DR EMBL; BC001275; AAH01275.1; -; mRNA. DR EMBL; BC035993; AAH35993.1; -; mRNA. DR CCDS; CCDS6645.1; -. DR PIR; A03080; LUHU. DR RefSeq; NP_000691.1; NM_000700.2. DR RefSeq; XP_011516911.1; XM_011518609.1. DR UniGene; Hs.494173; -. DR PDB; 1AIN; X-ray; 2.50 A; A=33-346. DR PDB; 1BO9; NMR; -; A=41-113. DR PDB; 1QLS; X-ray; 2.30 A; D=2-12. DR PDBsum; 1AIN; -. DR PDBsum; 1BO9; -. DR PDBsum; 1QLS; -. DR ProteinModelPortal; P04083; -. DR SMR; P04083; 2-344. DR BioGrid; 106798; 76. DR DIP; DIP-32875N; -. DR IntAct; P04083; 72. DR MINT; MINT-1212274; -. DR STRING; 9606.ENSP00000257497; -. DR DrugBank; DB00288; Amcinonide. DR DrugBank; DB01234; Dexamethasone. DR DrugBank; DB00741; Hydrocortisone. DR TCDB; 1.A.31.1.3; the annexin (annexin) family. DR iPTMnet; P04083; -. DR PhosphoSite; P04083; -. DR SwissPalm; P04083; -. DR BioMuta; ANXA1; -. DR DMDM; 113944; -. DR DOSAC-COBS-2DPAGE; P04083; -. DR REPRODUCTION-2DPAGE; IPI00218918; -. DR REPRODUCTION-2DPAGE; P04083; -. DR UCD-2DPAGE; P04083; -. DR EPD; P04083; -. DR PaxDb; P04083; -. DR PeptideAtlas; P04083; -. DR PRIDE; P04083; -. DR DNASU; 301; -. DR Ensembl; ENST00000257497; ENSP00000257497; ENSG00000135046. DR Ensembl; ENST00000376911; ENSP00000366109; ENSG00000135046. DR GeneID; 301; -. DR KEGG; hsa:301; -. DR CTD; 301; -. DR GeneCards; ANXA1; -. DR HGNC; HGNC:533; ANXA1. DR HPA; CAB013023; -. DR HPA; CAB035987; -. DR HPA; CAB058693; -. DR HPA; HPA011271; -. DR HPA; HPA011272; -. DR MIM; 151690; gene. DR neXtProt; NX_P04083; -. DR PharmGKB; PA24823; -. DR eggNOG; KOG0819; Eukaryota. DR eggNOG; ENOG410XPUN; LUCA. DR HOGENOM; HOG000158803; -. DR HOVERGEN; HBG061815; -. DR InParanoid; P04083; -. DR KO; K17091; -. DR OMA; IMVSRHE; -. DR OrthoDB; EOG74XS72; -. DR PhylomeDB; P04083; -. DR TreeFam; TF105452; -. DR Reactome; R-HSA-416476; G alpha (q) signalling events. DR Reactome; R-HSA-418594; G alpha (i) signalling events. DR Reactome; R-HSA-444473; Formyl peptide receptors bind formyl peptides and many other ligands. DR Reactome; R-HSA-445355; Smooth Muscle Contraction. DR SignaLink; P04083; -. DR ChiTaRS; ANXA1; human. DR EvolutionaryTrace; P04083; -. DR GeneWiki; Annexin_A1; -. DR GenomeRNAi; 301; -. DR NextBio; 1213; -. DR PRO; PR:P04083; -. DR Proteomes; UP000005640; Chromosome 9. DR Bgee; P04083; -. DR CleanEx; HS_ANXA1; -. DR ExpressionAtlas; P04083; baseline and differential. DR Genevisible; P04083; HS. DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB. DR GO; GO:0016323; C:basolateral plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL. DR GO; GO:0001533; C:cornified envelope; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell. DR GO; GO:0031901; C:early endosome membrane; ISS:UniProtKB. DR GO; GO:0005768; C:endosome; IDA:UniProtKB. DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB. DR GO; GO:0031313; C:extrinsic component of endosome membrane; ISS:UniProtKB. DR GO; GO:0031232; C:extrinsic component of external side of plasma membrane; IDA:UniProtKB. DR GO; GO:0019898; C:extrinsic component of membrane; IDA:UniProtKB. DR GO; GO:0005925; C:focal adhesion; IDA:UniProtKB. DR GO; GO:0016328; C:lateral plasma membrane; ISS:UniProtKB. DR GO; GO:0042629; C:mast cell granule; IEA:Ensembl. DR GO; GO:0031966; C:mitochondrial membrane; IEA:Ensembl. DR GO; GO:0031514; C:motile cilium; ISS:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL. DR GO; GO:0001891; C:phagocytic cup; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0043234; C:protein complex; IEA:Ensembl. DR GO; GO:0042383; C:sarcolemma; IEA:Ensembl. DR GO; GO:0031982; C:vesicle; IDA:UniProtKB. DR GO; GO:0036310; F:annealing helicase activity; IEA:Ensembl. DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB. DR GO; GO:0005544; F:calcium-dependent phospholipid binding; IDA:UniProtKB. DR GO; GO:0048306; F:calcium-dependent protein binding; IPI:AgBase. DR GO; GO:0033676; F:double-stranded DNA-dependent ATPase activity; IEA:Ensembl. DR GO; GO:0004386; F:helicase activity; IEA:Ensembl. DR GO; GO:0019834; F:phospholipase A2 inhibitor activity; IDA:UniProtKB. DR GO; GO:0005543; F:phospholipid binding; TAS:ProtInc. DR GO; GO:0030674; F:protein binding, bridging; IDA:UniProtKB. DR GO; GO:0005102; F:receptor binding; TAS:ProtInc. DR GO; GO:0003697; F:single-stranded DNA binding; IEA:Ensembl. DR GO; GO:0003727; F:single-stranded RNA binding; IEA:Ensembl. DR GO; GO:0005198; F:structural molecule activity; IDA:UniProtKB. DR GO; GO:0031532; P:actin cytoskeleton reorganization; IDA:UniProtKB. DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW. DR GO; GO:0046632; P:alpha-beta T cell differentiation; ISS:BHF-UCL. DR GO; GO:0050482; P:arachidonic acid secretion; IEA:Ensembl. DR GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:ProtInc. DR GO; GO:0071385; P:cellular response to glucocorticoid stimulus; IDA:BHF-UCL. DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IEA:Ensembl. DR GO; GO:0032508; P:DNA duplex unwinding; IEA:Ensembl. DR GO; GO:0036292; P:DNA rewinding; IEA:Ensembl. DR GO; GO:0031018; P:endocrine pancreas development; IEA:Ensembl. DR GO; GO:0044849; P:estrous cycle; IEA:Ensembl. DR GO; GO:0007187; P:G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger; IDA:UniProtKB. DR GO; GO:0042063; P:gliogenesis; IEA:Ensembl. DR GO; GO:0071621; P:granulocyte chemotaxis; IDA:UniProtKB. DR GO; GO:0070365; P:hepatocyte differentiation; IEA:Ensembl. DR GO; GO:0006954; P:inflammatory response; ISS:UniProtKB. DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW. DR GO; GO:0030073; P:insulin secretion; IEA:Ensembl. DR GO; GO:0030216; P:keratinocyte differentiation; IDA:UniProtKB. DR GO; GO:0002548; P:monocyte chemotaxis; IDA:UniProtKB. DR GO; GO:0006936; P:muscle contraction; TAS:Reactome. DR GO; GO:0014839; P:myoblast migration involved in skeletal muscle regeneration; IEA:Ensembl. DR GO; GO:0043066; P:negative regulation of apoptotic process; TAS:UniProtKB. DR GO; GO:0045920; P:negative regulation of exocytosis; IMP:UniProtKB. DR GO; GO:2000483; P:negative regulation of interleukin-8 secretion; IMP:BHF-UCL. DR GO; GO:1900138; P:negative regulation of phospholipase A2 activity; IEA:Ensembl. DR GO; GO:0045629; P:negative regulation of T-helper 2 cell differentiation; IDA:UniProtKB. DR GO; GO:0097350; P:neutrophil clearance; IMP:BHF-UCL. DR GO; GO:0001780; P:neutrophil homeostasis; IMP:BHF-UCL. DR GO; GO:0018149; P:peptide cross-linking; IDA:UniProtKB. DR GO; GO:0006909; P:phagocytosis; ISS:UniProtKB. DR GO; GO:1900087; P:positive regulation of G1/S transition of mitotic cell cycle; IEA:Ensembl. DR GO; GO:0032743; P:positive regulation of interleukin-2 production; IDA:UniProtKB. DR GO; GO:0033031; P:positive regulation of neutrophil apoptotic process; IEA:Ensembl. DR GO; GO:0031394; P:positive regulation of prostaglandin biosynthetic process; IEA:Ensembl. DR GO; GO:0042102; P:positive regulation of T cell proliferation; IDA:UniProtKB. DR GO; GO:0045627; P:positive regulation of T-helper 1 cell differentiation; IDA:UniProtKB. DR GO; GO:0031340; P:positive regulation of vesicle fusion; IDA:UniProtKB. DR GO; GO:0090303; P:positive regulation of wound healing; IDA:UniProtKB. DR GO; GO:0070459; P:prolactin secretion; IEA:Ensembl. DR GO; GO:0030850; P:prostate gland development; IEA:Ensembl. DR GO; GO:0008360; P:regulation of cell shape; IDA:UniProtKB. DR GO; GO:0046883; P:regulation of hormone secretion; IMP:UniProtKB. DR GO; GO:0050727; P:regulation of inflammatory response; ISS:UniProtKB. DR GO; GO:0032652; P:regulation of interleukin-1 production; ISS:UniProtKB. DR GO; GO:0002685; P:regulation of leukocyte migration; ISS:UniProtKB. DR GO; GO:0042493; P:response to drug; IEA:Ensembl. DR GO; GO:0032355; P:response to estradiol; IEA:Ensembl. DR GO; GO:0070555; P:response to interleukin-1; IEA:Ensembl. DR GO; GO:0043434; P:response to peptide hormone; IEA:Ensembl. DR GO; GO:0010165; P:response to X-ray; IEA:Ensembl. DR GO; GO:0007165; P:signal transduction; TAS:UniProtKB. DR Gene3D; 1.10.220.10; -; 4. DR InterPro; IPR001464; Annexin. DR InterPro; IPR018502; Annexin_repeat. DR InterPro; IPR018252; Annexin_repeat_CS. DR InterPro; IPR002388; AnnexinI. DR PANTHER; PTHR10502:SF17; PTHR10502:SF17; 1. DR Pfam; PF00191; Annexin; 4. DR PRINTS; PR00196; ANNEXIN. DR PRINTS; PR00197; ANNEXINI. DR SMART; SM00335; ANX; 4. DR PROSITE; PS00223; ANNEXIN; 4. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Adaptive immunity; Annexin; Calcium; KW Calcium/phospholipid-binding; Cell membrane; Cell projection; Cilium; KW Complete proteome; Cytoplasm; Cytoplasmic vesicle; KW Direct protein sequencing; Disulfide bond; Endosome; Immunity; KW Inflammatory response; Innate immunity; Isopeptide bond; Membrane; KW Metal-binding; Nucleus; Pharmaceutical; Phospholipase A2 inhibitor; KW Phosphoprotein; Reference proteome; Repeat; Secreted; Ubl conjugation. FT INIT_MET 1 1 Removed. {ECO:0000269|PubMed:3303336}. FT CHAIN 2 346 Annexin A1. FT /FTId=PRO_0000067460. FT REPEAT 51 111 Annexin 1. FT REPEAT 123 183 Annexin 2. FT REPEAT 207 267 Annexin 3. FT REPEAT 282 342 Annexin 4. FT METAL 59 59 Calcium 1; via carbonyl oxygen. FT {ECO:0000250|UniProtKB:P19619}. FT METAL 60 60 Calcium 1; via carbonyl oxygen. FT {ECO:0000250|UniProtKB:P19619}. FT METAL 62 62 Calcium 1. FT {ECO:0000250|UniProtKB:P19619}. FT METAL 97 97 Calcium 2; via carbonyl oxygen. FT {ECO:0000250|UniProtKB:P19619}. FT METAL 100 100 Calcium 2; via carbonyl oxygen. FT {ECO:0000250|UniProtKB:P19619}. FT METAL 105 105 Calcium 2. FT {ECO:0000250|UniProtKB:P19619}. FT METAL 127 127 Calcium 3; via carbonyl oxygen. FT {ECO:0000250|UniProtKB:P19619}. FT METAL 129 129 Calcium 3; via carbonyl oxygen. FT {ECO:0000250|UniProtKB:P19619}. FT METAL 131 131 Calcium 3; via carbonyl oxygen. FT {ECO:0000250|UniProtKB:P19619}. FT METAL 132 132 Calcium 4; via carbonyl oxygen. FT {ECO:0000250|UniProtKB:P19619}. FT METAL 134 134 Calcium 4. FT {ECO:0000250|UniProtKB:P19619}. FT METAL 171 171 Calcium 3. FT {ECO:0000250|UniProtKB:P19619}. FT METAL 210 210 Calcium 5; via carbonyl oxygen. FT {ECO:0000250|UniProtKB:P19619}. FT METAL 213 213 Calcium 5; via carbonyl oxygen. FT {ECO:0000250|UniProtKB:P19619}. FT METAL 215 215 Calcium 5; via carbonyl oxygen. FT {ECO:0000250|UniProtKB:P19619}. FT METAL 253 253 Calcium 6. FT {ECO:0000250|UniProtKB:P19619}. FT METAL 255 255 Calcium 5. FT {ECO:0000250|UniProtKB:P19619}. FT METAL 256 256 Calcium 6; via carbonyl oxygen. FT {ECO:0000250|UniProtKB:P19619}. FT METAL 261 261 Calcium 6. FT {ECO:0000250|UniProtKB:P19619}. FT METAL 286 286 Calcium 7; via carbonyl oxygen. FT {ECO:0000250|UniProtKB:P19619}. FT METAL 288 288 Calcium 7; via carbonyl oxygen. FT {ECO:0000250|UniProtKB:P19619}. FT METAL 290 290 Calcium 7; via carbonyl oxygen. FT {ECO:0000250|UniProtKB:P19619}. FT METAL 328 328 Calcium 8; via carbonyl oxygen. FT {ECO:0000250|UniProtKB:P19619}. FT METAL 330 330 Calcium 7. FT {ECO:0000250|UniProtKB:P19619}. FT METAL 331 331 Calcium 8; via carbonyl oxygen. FT {ECO:0000250|UniProtKB:P19619}. FT METAL 336 336 Calcium 8. FT {ECO:0000250|UniProtKB:P19619}. FT MOD_RES 2 2 N-acetylalanine. FT {ECO:0000269|PubMed:3303336}. FT MOD_RES 5 5 Phosphoserine; by TRPM7. FT {ECO:0000269|PubMed:15485879}. FT MOD_RES 21 21 Phosphotyrosine; by EGFR. FT {ECO:0000269|PubMed:2457390}. FT MOD_RES 27 27 Phosphoserine; by PKC. FT {ECO:0000269|PubMed:2457390}. FT MOD_RES 34 34 Phosphoserine. FT {ECO:0000244|PubMed:24275569}. FT MOD_RES 37 37 Phosphoserine. FT {ECO:0000244|PubMed:20068231}. FT MOD_RES 58 58 N6-acetyllysine. FT {ECO:0000250|UniProtKB:P10107}. FT MOD_RES 239 239 N6-acetyllysine. FT {ECO:0000244|PubMed:19608861}. FT MOD_RES 312 312 N6-acetyllysine. FT {ECO:0000244|PubMed:19608861}. FT DISULFID 324 343 {ECO:0000250|UniProtKB:P19619}. FT CROSSLNK 19 19 Isoglutamyl lysine isopeptide (Gln-Lys) FT (interchain with K-?). FT CROSSLNK 214 214 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2). FT {ECO:0000244|PubMed:25772364}. FT CROSSLNK 257 257 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO1). FT {ECO:0000250|UniProtKB:P10107}. FT MUTAGEN 27 27 S->A: Abolishes secretion and modulation FT of exocytosis. FT {ECO:0000269|PubMed:19625660}. FT MUTAGEN 34 34 S->A: No effect on secretion and FT modulation of exocytosis. FT {ECO:0000269|PubMed:19625660}. FT MUTAGEN 45 45 S->A: Abolishes secretion and nearly FT abolishes modulation of exocytosis. FT {ECO:0000269|PubMed:19625660}. FT HELIX 3 10 {ECO:0000244|PDB:1QLS}. FT HELIX 46 55 {ECO:0000244|PDB:1BO9}. FT STRAND 62 64 {ECO:0000244|PDB:1BO9}. FT HELIX 65 71 {ECO:0000244|PDB:1BO9}. FT HELIX 77 87 {ECO:0000244|PDB:1BO9}. FT HELIX 94 99 {ECO:0000244|PDB:1BO9}. FT HELIX 106 109 {ECO:0000244|PDB:1BO9}. FT HELIX 110 112 {ECO:0000244|PDB:1BO9}. SQ SEQUENCE 346 AA; 38714 MW; 14B42E1FA4178EC0 CRC64; MAMVSEFLKQ AWFIENEEQE YVQTVKSSKG GPGSAVSPYP TFNPSSDVAA LHKAIMVKGV DEATIIDILT KRNNAQRQQI KAAYLQETGK PLDETLKKAL TGHLEEVVLA LLKTPAQFDA DELRAAMKGL GTDEDTLIEI LASRTNKEIR DINRVYREEL KRDLAKDITS DTSGDFRNAL LSLAKGDRSE DFGVNEDLAD SDARALYEAG ERRKGTDVNV FNTILTTRSY PQLRRVFQKY TKYSKHDMNK VLDLELKGDI EKCLTAIVKC ATSKPAFFAE KLHQAMKGVG TRHKALIRIM VSRSEIDMND IKAFYQKMYG ISLCQAILDE TKGDYEKILV ALCGGN //