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   02-SEP-2008, entry version 121.
DE   RecName: Full=Annexin A1;
DE   AltName: Full=Annexin-1;
DE   AltName: Full=Annexin I;
DE   AltName: Full=Lipocortin I;
DE   AltName: Full=Calpactin II;
DE   AltName: Full=Chromobindin-9;
DE   AltName: Full=p35;
DE   AltName: Full=Phospholipase A2 inhibitory protein;
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;
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 AND SER-27.
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;
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=Epithelium;
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.
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   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   [13]
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.
CC   -!- INTERACTION:
CC       Q92796:DLG3; NbExp=1; IntAct=EBI-354007, EBI-80440;
CC       O75688:PPM1B; NbExp=1; IntAct=EBI-354007, EBI-1047039;
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.
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DR   EMBL; X05908; CAA29338.1; -; Other_RNA.
DR   EMBL; BC001275; AAH01275.1; -; mRNA.
DR   EMBL; BC035993; AAH35993.1; -; mRNA.
DR   PIR; A03080; LUHU.
DR   RefSeq; NP_000691.1; -.
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=1-12.
DR   PDBsum; 1AIN; -.
DR   PDBsum; 1BO9; -.
DR   PDBsum; 1QLS; -.
DR   SMR; P04083; 2-344.
DR   IntAct; P04083; -.
DR   PhosphoSite; P04083; -.
DR   DOSAC-COBS-2DPAGE; P04083; -.
DR   PHCI-2DPAGE; P04083; -.
DR   REPRODUCTION-2DPAGE; IPI00218918; -.
DR   REPRODUCTION-2DPAGE; P04083; -.
DR   PeptideAtlas; P04083; -.
DR   Ensembl; ENSG00000135046; Homo sapiens.
DR   GeneID; 301; -.
DR   KEGG; hsa:301; -.
DR   H-InvDB; HIX0008100; -.
DR   HGNC; HGNC:533; ANXA1.
DR   HPA; CAB013023; -.
DR   HPA; HPA011271; -.
DR   HPA; HPA011272; -.
DR   MIM; 151690; gene.
DR   PharmGKB; PA24823; -.
DR   HOGENOM; P04083; -.
DR   HOVERGEN; P04083; -.
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   LinkHub; P04083; -.
DR   ArrayExpress; P04083; -.
DR   CleanEx; HS_ANXA1; -.
DR   GermOnline; ENSG00000135046; Homo sapiens.
DR   GO; GO:0001533; C:cornified envelope; IDA:UniProtKB.
DR   GO; GO:0005737; C:cytoplasm; TAS:UniProtKB.
DR   GO; GO:0005509; F:calcium ion binding; TAS:ProtInc.
DR   GO; GO:0004859; F:phospholipase inhibitor activity; TAS:ProtInc.
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:0005198; F:structural molecule activity; IDA:UniProtKB.
DR   GO; GO:0006916; P:anti-apoptosis; TAS:UniProtKB.
DR   GO; GO:0006928; P:cell motility; TAS:ProtInc.
DR   GO; GO:0007166; P:cell surface receptor linked signal transdu...; TAS:ProtInc.
DR   GO; GO:0006954; P:inflammatory response; TAS:ProtInc.
DR   GO; GO:0030216; P:keratinocyte differentiation; IDA:UniProtKB.
DR   GO; GO:0006629; P:lipid metabolic process; TAS:ProtInc.
DR   GO; GO:0018149; P:peptide cross-linking; IDA:UniProtKB.
DR   InterPro; IPR001464; Annexin.
DR   InterPro; IPR002388; AnnexinI.
DR   Gene3D; G3DSA:1.10.220.10; Annexin; 4.
DR   PANTHER; PTHR10502; Annexin; 1.
DR   Pfam; PF00191; Annexin; 4.
DR   PRINTS; PR00196; ANNEXIN.
DR   PRINTS; PR00197; ANNEXINI.
DR   ProDom; PD000143; Annexin; 4.
DR   SMART; SM00335; ANX; 4.
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   Cytoplasm; Direct protein sequencing; Membrane; Nucleus;
KW   Phospholipase A2 inhibitor; Phosphoprotein; 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     207    207       Phosphotyrosine.
FT   CROSSLNK     19     19       Isoglutamyl lysine isopeptide (Gln-Lys)
FT                                (interchain with K-?).
FT   HELIX         3     10
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
//