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 28-NOV-2012, entry version 169. 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; 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]. RX MEDLINE=86146879; 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 MEDLINE=91369906; 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]. RX MEDLINE=93145967; PubMed=8425544; RX 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 MEDLINE=88309771; 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 MASS SPECTROMETRY. RX MEDLINE=87292145; 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 DIMERIZATION. RX MEDLINE=90104259; 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 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 [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-207, AND MASS RP SPECTROMETRY. RX PubMed=15592455; DOI=10.1038/nbt1046; RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., RA Zha X.-M., Polakiewicz R.D., Comb M.J.; RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer RT cells."; RL Nat. Biotechnol. 23:94-101(2005). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-21, AND MASS RP SPECTROMETRY. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., RA Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in RT signaling networks."; RL Cell 127:635-648(2006). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-39 AND TYR-207, AND MASS RP SPECTROMETRY. RC TISSUE=Lung carcinoma; RX PubMed=18083107; DOI=10.1016/j.cell.2007.11.025; RA Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., RA Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., RA Mitchell J., Wetzel R., Macneill J., Ren J.M., Yuan J., RA Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., RA Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.; RT "Global survey of phosphotyrosine signaling identifies oncogenic RT kinases in lung cancer."; RL Cell 131:1190-1203(2007). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-39 AND TYR-207, AND MASS RP SPECTROMETRY. RC TISSUE=Mammary epithelium; RX PubMed=19534553; DOI=10.1021/pr900044c; RA Heibeck T.H., Ding S.-J., Opresko L.K., Zhao R., Schepmoes A.A., RA Yang F., Tolmachev A.V., Monroe M.E., Camp D.G. II, Smith R.D., RA Wiley H.S., Qian W.-J.; RT "An extensive survey of tyrosine phosphorylation revealing new sites RT in human mammary epithelial cells."; RL J. Proteome Res. 8:3852-3861(2009). RN [13] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-161; LYS-239; LYS-250; RP LYS-281 AND LYS-312, AND MASS SPECTROMETRY. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., RA 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 [14] 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 [15] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS). RX MEDLINE=93200922; PubMed=8453382; 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 [16] RP STRUCTURE BY NMR OF 41-113. RX MEDLINE=99115644; 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). CC -!- FUNCTION: Calcium/phospholipid-binding protein which promotes CC membrane fusion and is involved in exocytosis. This protein CC regulates phospholipase A2 activity. It seems to bind from two to CC four calcium ions with high affinity. CC -!- SUBUNIT: Homodimer in placenta (20%); linked by CC transglutamylation. Interacts with DYSF (By similarity). 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 (By similarity). Cytoplasm (By CC similarity). Cell projection, cilium (By similarity). Basolateral CC cell membrane (By similarity). Note=Found in the cilium, nucleus CC and basolateral cell membrane of ciliated cells in the tracheal CC endothelium (By similarity). Found in the cytoplasm of type II CC pneumocytes and alveolar macrophages (By similarity). CC -!- DOMAIN: A pair of annexin repeats may form one binding site for CC calcium and phospholipid. CC -!- PTM: Phosphorylated by protein kinase C, epidermal growth factor CC receptor/kinase and TRPM7. Phosphorylation results in loss of the CC inhibitory activity. CC -!- SIMILARITY: Belongs to the annexin family. CC -!- SIMILARITY: Contains 4 annexin repeats. 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 IPI; IPI00218918; -. DR PIR; A03080; LUHU. DR RefSeq; NP_000691.1; NM_000700.1. 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 DIP; DIP-32875N; -. DR IntAct; P04083; 17. DR MINT; MINT-1212274; -. DR STRING; P04083; -. DR TCDB; 1.A.31.1.3; annexin family. DR PhosphoSite; P04083; -. DR DMDM; 113944; -. DR DOSAC-COBS-2DPAGE; P04083; -. DR PHCI-2DPAGE; P04083; -. DR REPRODUCTION-2DPAGE; IPI00218918; -. DR REPRODUCTION-2DPAGE; P04083; -. DR UCD-2DPAGE; 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 UCSC; uc004ajf.1; human. DR CTD; 301; -. DR GeneCards; GC09P075766; -. DR HGNC; HGNC:533; ANXA1. DR HPA; CAB013023; -. DR HPA; CAB035987; -. DR HPA; HPA011271; -. DR HPA; HPA011272; -. DR MIM; 151690; gene. DR neXtProt; NX_P04083; -. DR PharmGKB; PA24823; -. DR eggNOG; NOG282829; -. DR HOGENOM; HOG000158803; -. DR HOVERGEN; HBG061815; -. DR InParanoid; P04083; -. DR OMA; VFQKYSK; -. DR OrthoDB; EOG48WC2C; -. DR PhylomeDB; P04083; -. DR Reactome; REACT_111102; Signal Transduction. DR DrugBank; DB00240; Alclometasone. DR DrugBank; DB00288; Amcinonide. DR DrugBank; DB00394; Beclomethasone. DR DrugBank; DB00443; Betamethasone. DR DrugBank; DB01013; Clobetasol. DR DrugBank; DB00838; Clocortolone. DR DrugBank; DB01260; Desonide. DR DrugBank; DB00547; Desoximetasone. DR DrugBank; DB01234; Dexamethasone. DR DrugBank; DB00223; Diflorasone. DR DrugBank; DB00663; Flumethasone Pivalate. DR DrugBank; DB00596; Halobetasol Propionate. DR DrugBank; DB00769; Hydrocortamate. DR DrugBank; DB00741; Hydrocortisone. DR DrugBank; DB00873; Loteprednol Etabonate. DR DrugBank; DB00959; Methylprednisolone. DR DrugBank; DB00764; Mometasone. DR DrugBank; DB01130; Prednicarbate. DR DrugBank; DB00635; Prednisone. DR DrugBank; DB00896; Rimexolone. DR DrugBank; DB00620; Triamcinolone. DR EvolutionaryTrace; P04083; -. DR GenomeRNAi; 301; -. DR NextBio; 1213; -. DR ArrayExpress; P04083; -. DR Bgee; P04083; -. DR CleanEx; HS_ANXA1; -. DR Genevestigator; P04083; -. DR GermOnline; ENSG00000135046; Homo sapiens. DR GO; GO:0016323; C:basolateral plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005929; C:cilium; IEA:UniProtKB-SubCell. DR GO; GO:0001533; C:cornified envelope; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; TAS:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IEA:Compara. DR GO; GO:0031966; C:mitochondrial membrane; IEA:Compara. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0043234; C:protein complex; IEA:Compara. DR GO; GO:0042383; C:sarcolemma; IEA:Compara. DR GO; GO:0005509; F:calcium ion binding; TAS:ProtInc. DR GO; GO:0005544; F:calcium-dependent phospholipid binding; IDA:UniProtKB. DR GO; GO:0019834; F:phospholipase A2 inhibitor activity; IDA:BHF-UCL. DR GO; GO:0003697; F:single-stranded DNA binding; IEA:Compara. DR GO; GO:0003727; F:single-stranded RNA binding; IEA:Compara. DR GO; GO:0005198; F:structural molecule activity; IDA:UniProtKB. DR GO; GO:0046632; P:alpha-beta T cell differentiation; ISS:BHF-UCL. DR GO; GO:0006916; P:anti-apoptosis; TAS:UniProtKB. DR GO; GO:0050482; P:arachidonic acid secretion; IEA:Compara. DR GO; GO:0007049; P:cell cycle; IEA:Compara. DR GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:ProtInc. DR GO; GO:0006928; P:cellular component movement; 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:Compara. DR GO; GO:0031018; P:endocrine pancreas development; IEA:Compara. DR GO; GO:0060206; P:estrous cycle phase; IEA:Compara. DR GO; GO:0042063; P:gliogenesis; IEA:Compara. DR GO; GO:0070365; P:hepatocyte differentiation; IEA:Compara. DR GO; GO:0006954; P:inflammatory response; TAS:ProtInc. DR GO; GO:0030073; P:insulin secretion; IEA:Compara. DR GO; GO:0030216; P:keratinocyte differentiation; IDA:UniProtKB. DR GO; GO:0002674; P:negative regulation of acute inflammatory response; IEA:Compara. DR GO; GO:0050709; P:negative regulation of protein secretion; IEA:Compara. DR GO; GO:0097350; P:neutrophil clearance; IMP:BHF-UCL. DR GO; GO:0018149; P:peptide cross-linking; IDA:UniProtKB. DR GO; GO:0043065; P:positive regulation of apoptotic process; IEA:Compara. DR GO; GO:0031394; P:positive regulation of prostaglandin biosynthetic process; IEA:Compara. DR GO; GO:0031340; P:positive regulation of vesicle fusion; IDA:UniProtKB. DR GO; GO:0042127; P:regulation of cell proliferation; IEA:Compara. DR GO; GO:0042493; P:response to drug; IEA:Compara. DR GO; GO:0032355; P:response to estradiol stimulus; IEA:Compara. DR GO; GO:0070555; P:response to interleukin-1; IEA:Compara. DR GO; GO:0014070; P:response to organic cyclic compound; IEA:Compara. DR GO; GO:0043434; P:response to peptide hormone stimulus; IEA:Compara. DR GO; GO:0010165; P:response to X-ray; IEA:Compara. DR Gene3D; 1.10.220.10; Annexin; 4. DR InterPro; IPR001464; Annexin. DR InterPro; IPR018502; Annexin_repeat. DR InterPro; IPR018252; Annexin_repeat_CS. DR InterPro; IPR002388; AnnexinI. DR PANTHER; PTHR10502; PTHR10502; 1. DR Pfam; PF00191; Annexin; 4. DR PRINTS; PR00196; ANNEXIN. DR PRINTS; PR00197; ANNEXINI. DR SMART; SM00335; ANX; 4. DR SUPFAM; SSF47874; Annexin; 1. DR PROSITE; PS00223; ANNEXIN; 4. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Annexin; Calcium; KW Calcium/phospholipid-binding; Cell membrane; Cell projection; Cilium; KW Complete proteome; Cytoplasm; Direct protein sequencing; KW Isopeptide bond; Membrane; Nucleus; Phospholipase A2 inhibitor; KW Phosphoprotein; Reference proteome; Repeat. FT INIT_MET 1 1 Removed. 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 MOD_RES 2 2 N-acetylalanine. FT MOD_RES 5 5 Phosphoserine; by TRPM7. FT MOD_RES 21 21 Phosphotyrosine; by EGFR. FT MOD_RES 24 24 Phosphothreonine. FT MOD_RES 27 27 Phosphoserine; by PKC. FT MOD_RES 39 39 Phosphotyrosine. FT MOD_RES 161 161 N6-acetyllysine. FT MOD_RES 207 207 Phosphotyrosine. FT MOD_RES 239 239 N6-acetyllysine. FT MOD_RES 250 250 N6-acetyllysine. FT MOD_RES 281 281 N6-acetyllysine. FT MOD_RES 312 312 N6-acetyllysine. FT CROSSLNK 19 19 Isoglutamyl lysine isopeptide (Gln-Lys) FT (interchain with K-?). FT HELIX 3 10 FT HELIX 46 55 FT STRAND 62 64 FT HELIX 65 71 FT HELIX 77 87 FT HELIX 94 99 FT HELIX 106 109 FT HELIX 110 112 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 //