Full text data of ANXA1
ANXA1
(ANX1, LPC1)
[Confidence: high (present in two of the MS resources)]
Annexin A1 (Annexin I; Annexin-1; Calpactin II; Calpactin-2; Chromobindin-9; Lipocortin I; Phospholipase A2 inhibitory protein; p35)
Annexin A1 (Annexin I; Annexin-1; Calpactin II; Calpactin-2; Chromobindin-9; Lipocortin I; Phospholipase A2 inhibitory protein; p35)
hRBCD
IPI00218918
IPI00218918 annexin I annexin I membrane n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a 1 n/a membrane bound n/a found at its expected molecular weight found at molecular weight
IPI00218918 annexin I annexin I membrane n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a 1 n/a membrane bound n/a found at its expected molecular weight found at molecular weight
UniProt
P04083
ID ANXA1_HUMAN Reviewed; 346 AA.
AC P04083;
DT 01-NOV-1986, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 181.
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 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].
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 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 DIMERIZATION.
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 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 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 [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-239 AND LYS-312, AND MASS
RP SPECTROMETRY.
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 [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, AND MASS
RP SPECTROMETRY.
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 [12]
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 [13]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
RX 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 [14]
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).
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 -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/ANXA1ID653ch9q21.html";
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DR EMBL; X05908; CAA29338.1; -; mRNA.
DR EMBL; BC001275; AAH01275.1; -; mRNA.
DR EMBL; BC035993; AAH35993.1; -; mRNA.
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; 34.
DR MINT; MINT-1212274; -.
DR STRING; 9606.ENSP00000257497; -.
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 TCDB; 1.A.31.1.3; the annexin (annexin) family.
DR PhosphoSite; P04083; -.
DR DMDM; 113944; -.
DR DOSAC-COBS-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; CAB058693; -.
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 KO; K17091; -.
DR OMA; MNDIKAC; -.
DR OrthoDB; EOG74XS72; -.
DR PhylomeDB; P04083; -.
DR Reactome; REACT_111102; Signal Transduction.
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 ArrayExpress; P04083; -.
DR Bgee; P04083; -.
DR CleanEx; HS_ANXA1; -.
DR Genevestigator; P04083; -.
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:0005615; C:extracellular space; IEA:Ensembl.
DR GO; GO:0070062; C:extracellular vesicular exosome; IDA:UniProtKB.
DR GO; GO:0031966; C:mitochondrial membrane; IEA:Ensembl.
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:Ensembl.
DR GO; GO:0042383; C:sarcolemma; IEA:Ensembl.
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:UniProtKB.
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:0046632; P:alpha-beta T cell differentiation; ISS:BHF-UCL.
DR GO; GO:0050482; P:arachidonic acid secretion; IEA:Ensembl.
DR GO; GO:0007049; P:cell cycle; IEA:Ensembl.
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:Ensembl.
DR GO; GO:0031018; P:endocrine pancreas development; IEA:Ensembl.
DR GO; GO:0060206; P:estrous cycle phase; IEA:Ensembl.
DR GO; GO:0042063; P:gliogenesis; IEA:Ensembl.
DR GO; GO:0070365; P:hepatocyte differentiation; IEA:Ensembl.
DR GO; GO:0006954; P:inflammatory response; TAS:ProtInc.
DR GO; GO:0030073; P:insulin secretion; IEA:Ensembl.
DR GO; GO:0030216; P:keratinocyte differentiation; IDA:UniProtKB.
DR GO; GO:0002674; P:negative regulation of acute inflammatory response; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; TAS:UniProtKB.
DR GO; GO:0050709; P:negative regulation of protein secretion; IEA:Ensembl.
DR GO; GO:0097350; P:neutrophil clearance; IMP:BHF-UCL.
DR GO; GO:0018149; P:peptide cross-linking; 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:0031340; P:positive regulation of vesicle fusion; IDA:UniProtKB.
DR GO; GO:0042127; P:regulation of cell proliferation; IEA:Ensembl.
DR GO; GO:0042493; P:response to drug; IEA:Ensembl.
DR GO; GO:0032355; P:response to estradiol stimulus; IEA:Ensembl.
DR GO; GO:0070555; P:response to interleukin-1; IEA:Ensembl.
DR GO; GO:0043434; P:response to peptide hormone stimulus; IEA:Ensembl.
DR GO; GO:0010165; P:response to X-ray; IEA:Ensembl.
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 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; 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 37 37 Phosphoserine.
FT MOD_RES 239 239 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
//
ID ANXA1_HUMAN Reviewed; 346 AA.
AC P04083;
DT 01-NOV-1986, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 181.
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 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].
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 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 DIMERIZATION.
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 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 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 [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-239 AND LYS-312, AND MASS
RP SPECTROMETRY.
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 [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, AND MASS
RP SPECTROMETRY.
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 [12]
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 [13]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
RX 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 [14]
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).
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 -!- 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 http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; X05908; CAA29338.1; -; mRNA.
DR EMBL; BC001275; AAH01275.1; -; mRNA.
DR EMBL; BC035993; AAH35993.1; -; mRNA.
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; 34.
DR MINT; MINT-1212274; -.
DR STRING; 9606.ENSP00000257497; -.
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 TCDB; 1.A.31.1.3; the annexin (annexin) family.
DR PhosphoSite; P04083; -.
DR DMDM; 113944; -.
DR DOSAC-COBS-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; CAB058693; -.
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 KO; K17091; -.
DR OMA; MNDIKAC; -.
DR OrthoDB; EOG74XS72; -.
DR PhylomeDB; P04083; -.
DR Reactome; REACT_111102; Signal Transduction.
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 ArrayExpress; P04083; -.
DR Bgee; P04083; -.
DR CleanEx; HS_ANXA1; -.
DR Genevestigator; P04083; -.
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:0005615; C:extracellular space; IEA:Ensembl.
DR GO; GO:0070062; C:extracellular vesicular exosome; IDA:UniProtKB.
DR GO; GO:0031966; C:mitochondrial membrane; IEA:Ensembl.
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:Ensembl.
DR GO; GO:0042383; C:sarcolemma; IEA:Ensembl.
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:UniProtKB.
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:0046632; P:alpha-beta T cell differentiation; ISS:BHF-UCL.
DR GO; GO:0050482; P:arachidonic acid secretion; IEA:Ensembl.
DR GO; GO:0007049; P:cell cycle; IEA:Ensembl.
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:Ensembl.
DR GO; GO:0031018; P:endocrine pancreas development; IEA:Ensembl.
DR GO; GO:0060206; P:estrous cycle phase; IEA:Ensembl.
DR GO; GO:0042063; P:gliogenesis; IEA:Ensembl.
DR GO; GO:0070365; P:hepatocyte differentiation; IEA:Ensembl.
DR GO; GO:0006954; P:inflammatory response; TAS:ProtInc.
DR GO; GO:0030073; P:insulin secretion; IEA:Ensembl.
DR GO; GO:0030216; P:keratinocyte differentiation; IDA:UniProtKB.
DR GO; GO:0002674; P:negative regulation of acute inflammatory response; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; TAS:UniProtKB.
DR GO; GO:0050709; P:negative regulation of protein secretion; IEA:Ensembl.
DR GO; GO:0097350; P:neutrophil clearance; IMP:BHF-UCL.
DR GO; GO:0018149; P:peptide cross-linking; 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:0031340; P:positive regulation of vesicle fusion; IDA:UniProtKB.
DR GO; GO:0042127; P:regulation of cell proliferation; IEA:Ensembl.
DR GO; GO:0042493; P:response to drug; IEA:Ensembl.
DR GO; GO:0032355; P:response to estradiol stimulus; IEA:Ensembl.
DR GO; GO:0070555; P:response to interleukin-1; IEA:Ensembl.
DR GO; GO:0043434; P:response to peptide hormone stimulus; IEA:Ensembl.
DR GO; GO:0010165; P:response to X-ray; IEA:Ensembl.
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 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; 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 37 37 Phosphoserine.
FT MOD_RES 239 239 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
//
MIM
151690
*RECORD*
*FIELD* NO
151690
*FIELD* TI
*151690 ANNEXIN A1; ANXA1
;;ANNEXIN I; ANX1;;
LIPOCORTIN I; LPC1;;
CALPACTIN II
*FIELD* TX
read more
CLONING
The antiinflammatory action of glucocorticoids has been attributed to
the induction of a group of proteins, collectively called lipocortin,
that inhibit phospholipase A2. These proteins are thought to control the
biosynthesis of potent mediators of inflammation, prostaglandins and
leukotrienes, by inhibiting release of their common precursor,
arachidonic acid, a process that requires hydrolysis of phospholipids by
phospholipase A2. Lipocortin-like proteins have been isolated from
monocytes, neutrophils, renal medullary cells, and other cell types. The
predominant active form has an apparent relative molecular mass of
40,000. Partially purified lipocortin mimics the effect of steroids and
mediates antiinflammatory activity in various in vivo model systems.
Using amino acid sequence information from purified rat lipocortin,
Wallner et al. (1986) cloned cDNA for human lipocortin and expressed the
gene in E. coli. They confirmed that LPC is a potent inhibitor of
phospholipase A2. Lipocortin I belongs to the family of annexins, which
are structurally related proteins that have a molecular mass of
approximately 35,000 to 40,000. They undergo Ca(2+)-dependent binding to
phospholipids that are preferentially located on the cytosolic face of
the plasma membrane. The individual proteins in this family have been
discovered by investigators with various goals in mind and have been
given a variety of names (Kaplan et al., 1988).
Horlick et al. (1991) isolated overlapping mouse genomic clones for
Lipo1. The gene in the mouse encodes a protein of 346 amino acid
residues.
GENE STRUCTURE
Horlick et al. (1991) demonstrated that the mouse Lipo1 gene spans about
17 kb and is divided into 13 exons. Horlick et al. (1991) pointed out a
similarity in gene structure between mouse Lipo1 and Lipo2 (151740),
suggesting that they have a recent evolutionary ancestor.
GENE FAMILY
Crompton et al. (1988) reviewed the lipocortin/calpactin family of
proteins. Pepinsky et al. (1988) described the characteristics of 3
proteins they called lipocortin III, lipocortin V, and lipocortin VI.
Lipocortins III and IV are apparently identical. Shohat et al. (1989)
advanced the hypothesis that familial Mediterranean fever (FMF; 249100)
patients are homozygous for a mutant allele for one of the lipocortin
genes.
MAPPING
Huebner et al. (1987, 1988) mapped the ANXA1 gene to 9q11-q22 by
chromosomal in situ hybridization and segregation analysis in somatic
cell hybrids using a cDNA clone. By analysis of recombinant inbred
strains, Horlick et al. (1991) showed that the Lipo1 gene is located on
mouse chromosome 19.
GENE FUNCTION
Walther et al. (2000) showed that ANXA1 acts through the formyl peptide
receptor (FPR; 136537) on human neutrophils. Peptides derived from the
unique N-terminal domain of ANXA1 serve as FPR ligands and trigger
different signaling pathways in a dose-dependent manner. Lower peptide
concentrations possibly found in inflammatory situations elicit Ca(2+)
transients without fully activating the mitogen-activated protein kinase
pathway. This causes a specific inhibition of the transendothelial
migration of neutrophils and a desensitization of neutrophils toward a
chemoattractant challenge. These findings identified ANXA1 peptides as
novel, endogenous FPR ligands and established a mechanistic basis of
ANXA1-mediated antiinflammatory effects.
Perretti et al. (2002) reported that inhibition of polymorphonuclear
neutrophil infiltration by aspirin and dexamethasone is a property
shared by aspirin-triggered lipoxins and the glucocorticoid-induced
ANXA1-derived peptides that are both generated in vivo and act at the
lipoxin A4 receptor (FPRL1; 136538) to halt polymorphonuclear neutrophil
diapedesis. These structurally diverse ligands specifically interact
directly with recombinant human ALXR demonstrated by specific
radioligand binding and function as well as immunoprecipitation of
polymorphonuclear neutrophil receptors. In addition, the combination of
both aspirin-triggered lipoxins and ANXA1-derived peptides limited
polymorphonuclear neutrophil infiltration and reduced production of
inflammatory mediators (i.e., prostaglandins and chemokines) in vivo.
Perretti et al. (2002) concluded that the results indicated functional
redundancies in endogenous lipid and peptide antiinflammatory circuits
that are spatially and temporally separate, where both aspirin-triggered
lipoxins and specific ANXA1-derived peptides act in concert at ALXR to
downregulate polymorphonuclear neutrophil recruitment to inflammatory
loci.
Oh et al. (2004) described a hypothesis-driven, systems biology approach
to identifying a small subset of proteins induced at the tissue-blood
interface that are inherently accessible to antibodies injected
intravenously. They used subcellular fractionation, subtractive
proteomics, and bioinformatics to identify endothelial cell surface
proteins exhibiting restricted tissue distribution and apparent tissue
modulation. Expression profiling and gamma-scintigraphic imaging with
antibodies established 2 of these proteins, aminopeptidase-P (602443)
and annexin A1, as selective in vivo targets for antibodies in lung and
solid tumors, respectively. Radioimmunotherapy to annexin A1 destroyed
tumors and increased animal survival.
Using mice in 3 distinct models of T cell-mediated inflammation, Yang et
al. (2013) showed that AnxA1 deficiency significantly increased
antigen-induced T cell proliferation and the resulting inflammation. In
a contact hypersensitivity model, there was increased adhesion of T
cells, including those expressing Ror-gamma-t (RORC; 602943) and IL17a
(603149), and neutrophils in the dermal microvasculature. In
collagen-induced arthritis, susceptibility was increased as was
antigen-specific T cell activation. In delayed hypersensitivity, there
was increased release of IL17 and Ifng (147570). Transfer of AnxA1 -/- T
cells to wildtype mice resulted in increased inflammatory responses.
Yang et al. (2013) concluded that T cell-expressed AnxA1 attenuates T
cell-driven inflammatory responses via effects on intracellular
signaling, proliferation, and Th1/Th17 cytokine release.
*FIELD* RF
1. Crompton, M. R.; Moss, S. E.; Crumpton, M. J.: Diversity in the
lipocortin/calpactin family. Cell 55: 1-3, 1988.
2. Horlick, K. R.; Cheng, I. C.; Wong, W. T.; Wakeland, E. K.; Nick,
H. S.: Mouse lipocortin I gene structure and chromosomal assignment:
gene duplication and the origins of a gene family. Genomics 10:
365-374, 1991.
3. Huebner, K.; Cannizzaro, L. A.; Croce, C. M.; Frey, A. Z.; Wallner,
B. P.; Hecht, B. K.; Hecht, F.: Chromosome localization of the human
genes for lipocortin I and the lipocortin II family. (Abstract) Cytogenet.
Cell Genet. 46: 631 only, 1987.
4. Huebner, K.; Cannizzaro, L. A.; Frey, A. Z.; Hecht, B. K.; Hecht,
F.; Croce, C. M.; Wallner, B. P.: Chromosomal localization of the
human genes for lipocortin I and lipocortin II. Oncogene Res. 2:
299-310, 1988.
5. Kaplan, R.; Jaye, M.; Burgess, W. H.; Schlaepfer, D. D.; Haigler,
H. T.: Cloning and expression of cDNA for human endonexin II, a Ca(2+)
and phospholipid binding protein. J. Biol. Chem. 263: 8037-8043,
1988.
6. Oh, P.; Li, Y.; Yu, J.; Durr, E.; Krasinska, K. M.; Carver, L.
A.; Testa, J. E.; Schnitzer, J. E.: Subtractive proteomic mapping
of the endothelial surface in lung and solid tumours for tissue-specific
therapy. Nature 429: 629-635, 2004.
7. Pepinsky, R. B.; Tizard, R.; Mattaliano, R. J.; Sinclair, L. K.;
Miller, G. T.; Browning, J. L.; Chow, E. P.; Burne, C.; Huang, K.-S.;
Pratt, D.; Wachter, L.; Hession, C.; Frey, A. Z.; Wallner, B. P.:
Five distinct calcium and phospholipid binding proteins share homology
with lipocortin I. J. Biol. Chem. 263: 10799-10811, 1988.
8. Perretti, M.; Chiang, N.; La, M.; Fierro, I. M.; Marullo, S.; Getting,
S. J.; Solito, E.; Serhan, C. N.: Endogenous lipid- and peptide-derived
anti-inflammatory pathways generated with glucocorticoid and aspirin
treatment activate the lipoxin A(4) receptor. Nature Med. 8: 1296-1302,
2002.
9. Shohat, M.; Korenberg, J. R.; Schwabe, A. D.; Rotter, J. I.: Hypothesis:
familial Mediterranean fever--a genetic disorder of the lipocortin
family? Am. J. Med. Genet. 34: 163-167, 1989.
10. Wallner, B. P.; Mattaliano, R. J.; Hession, C.; Cate, R. L.; Tizard,
R.; Sinclair, L. K.; Foeller, C.; Chow, E. P.; Browning, J. L.; Ramachandran,
K. L.; Pepinsky, R. B.: Cloning and expression of human lipocortin,
a phospholipase A2 inhibitor with potential anti-inflammatory activity. Nature 320:
77-81, 1986.
11. Walther, A.; Riehemann, K.; Gerke, V.: A novel ligand of the
formyl peptide receptor: annexin I regulates neutrophil extravasation
by interacting with the FPR. Molec. Cell 5: 831-840, 2000.
12. Yang, Y. H.; Song, W.; Deane, J. A.; Kao, W.; Ooi, J. D.; Ngo,
D.; Kitching, A. R.; Morand, E. F.; Hickey, M. J.: Deficiency of
annexin A1 in CD4+ T cells exacerbates T cell-dependent inflammation. J.
Immun. 190: 997-1007, 2013.
*FIELD* CN
Paul J. Converse - updated: 07/31/2013
Ada Hamosh - updated: 7/26/2004
Ada Hamosh - updated: 11/15/2002
Stylianos E. Antonarakis - updated: 6/21/2000
*FIELD* CD
Victor A. McKusick: 6/25/1986
*FIELD* ED
alopez: 07/31/2013
alopez: 7/26/2004
terry: 7/26/2004
alopez: 11/18/2002
terry: 11/15/2002
mgross: 6/21/2000
mgross: 9/17/1999
terry: 5/3/1999
alopez: 9/23/1998
dkim: 9/11/1998
carol: 3/20/1998
carol: 9/4/1992
supermim: 3/16/1992
carol: 5/22/1991
carol: 3/20/1991
supermim: 3/20/1990
supermim: 2/9/1990
*RECORD*
*FIELD* NO
151690
*FIELD* TI
*151690 ANNEXIN A1; ANXA1
;;ANNEXIN I; ANX1;;
LIPOCORTIN I; LPC1;;
CALPACTIN II
*FIELD* TX
read more
CLONING
The antiinflammatory action of glucocorticoids has been attributed to
the induction of a group of proteins, collectively called lipocortin,
that inhibit phospholipase A2. These proteins are thought to control the
biosynthesis of potent mediators of inflammation, prostaglandins and
leukotrienes, by inhibiting release of their common precursor,
arachidonic acid, a process that requires hydrolysis of phospholipids by
phospholipase A2. Lipocortin-like proteins have been isolated from
monocytes, neutrophils, renal medullary cells, and other cell types. The
predominant active form has an apparent relative molecular mass of
40,000. Partially purified lipocortin mimics the effect of steroids and
mediates antiinflammatory activity in various in vivo model systems.
Using amino acid sequence information from purified rat lipocortin,
Wallner et al. (1986) cloned cDNA for human lipocortin and expressed the
gene in E. coli. They confirmed that LPC is a potent inhibitor of
phospholipase A2. Lipocortin I belongs to the family of annexins, which
are structurally related proteins that have a molecular mass of
approximately 35,000 to 40,000. They undergo Ca(2+)-dependent binding to
phospholipids that are preferentially located on the cytosolic face of
the plasma membrane. The individual proteins in this family have been
discovered by investigators with various goals in mind and have been
given a variety of names (Kaplan et al., 1988).
Horlick et al. (1991) isolated overlapping mouse genomic clones for
Lipo1. The gene in the mouse encodes a protein of 346 amino acid
residues.
GENE STRUCTURE
Horlick et al. (1991) demonstrated that the mouse Lipo1 gene spans about
17 kb and is divided into 13 exons. Horlick et al. (1991) pointed out a
similarity in gene structure between mouse Lipo1 and Lipo2 (151740),
suggesting that they have a recent evolutionary ancestor.
GENE FAMILY
Crompton et al. (1988) reviewed the lipocortin/calpactin family of
proteins. Pepinsky et al. (1988) described the characteristics of 3
proteins they called lipocortin III, lipocortin V, and lipocortin VI.
Lipocortins III and IV are apparently identical. Shohat et al. (1989)
advanced the hypothesis that familial Mediterranean fever (FMF; 249100)
patients are homozygous for a mutant allele for one of the lipocortin
genes.
MAPPING
Huebner et al. (1987, 1988) mapped the ANXA1 gene to 9q11-q22 by
chromosomal in situ hybridization and segregation analysis in somatic
cell hybrids using a cDNA clone. By analysis of recombinant inbred
strains, Horlick et al. (1991) showed that the Lipo1 gene is located on
mouse chromosome 19.
GENE FUNCTION
Walther et al. (2000) showed that ANXA1 acts through the formyl peptide
receptor (FPR; 136537) on human neutrophils. Peptides derived from the
unique N-terminal domain of ANXA1 serve as FPR ligands and trigger
different signaling pathways in a dose-dependent manner. Lower peptide
concentrations possibly found in inflammatory situations elicit Ca(2+)
transients without fully activating the mitogen-activated protein kinase
pathway. This causes a specific inhibition of the transendothelial
migration of neutrophils and a desensitization of neutrophils toward a
chemoattractant challenge. These findings identified ANXA1 peptides as
novel, endogenous FPR ligands and established a mechanistic basis of
ANXA1-mediated antiinflammatory effects.
Perretti et al. (2002) reported that inhibition of polymorphonuclear
neutrophil infiltration by aspirin and dexamethasone is a property
shared by aspirin-triggered lipoxins and the glucocorticoid-induced
ANXA1-derived peptides that are both generated in vivo and act at the
lipoxin A4 receptor (FPRL1; 136538) to halt polymorphonuclear neutrophil
diapedesis. These structurally diverse ligands specifically interact
directly with recombinant human ALXR demonstrated by specific
radioligand binding and function as well as immunoprecipitation of
polymorphonuclear neutrophil receptors. In addition, the combination of
both aspirin-triggered lipoxins and ANXA1-derived peptides limited
polymorphonuclear neutrophil infiltration and reduced production of
inflammatory mediators (i.e., prostaglandins and chemokines) in vivo.
Perretti et al. (2002) concluded that the results indicated functional
redundancies in endogenous lipid and peptide antiinflammatory circuits
that are spatially and temporally separate, where both aspirin-triggered
lipoxins and specific ANXA1-derived peptides act in concert at ALXR to
downregulate polymorphonuclear neutrophil recruitment to inflammatory
loci.
Oh et al. (2004) described a hypothesis-driven, systems biology approach
to identifying a small subset of proteins induced at the tissue-blood
interface that are inherently accessible to antibodies injected
intravenously. They used subcellular fractionation, subtractive
proteomics, and bioinformatics to identify endothelial cell surface
proteins exhibiting restricted tissue distribution and apparent tissue
modulation. Expression profiling and gamma-scintigraphic imaging with
antibodies established 2 of these proteins, aminopeptidase-P (602443)
and annexin A1, as selective in vivo targets for antibodies in lung and
solid tumors, respectively. Radioimmunotherapy to annexin A1 destroyed
tumors and increased animal survival.
Using mice in 3 distinct models of T cell-mediated inflammation, Yang et
al. (2013) showed that AnxA1 deficiency significantly increased
antigen-induced T cell proliferation and the resulting inflammation. In
a contact hypersensitivity model, there was increased adhesion of T
cells, including those expressing Ror-gamma-t (RORC; 602943) and IL17a
(603149), and neutrophils in the dermal microvasculature. In
collagen-induced arthritis, susceptibility was increased as was
antigen-specific T cell activation. In delayed hypersensitivity, there
was increased release of IL17 and Ifng (147570). Transfer of AnxA1 -/- T
cells to wildtype mice resulted in increased inflammatory responses.
Yang et al. (2013) concluded that T cell-expressed AnxA1 attenuates T
cell-driven inflammatory responses via effects on intracellular
signaling, proliferation, and Th1/Th17 cytokine release.
*FIELD* RF
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*FIELD* CN
Paul J. Converse - updated: 07/31/2013
Ada Hamosh - updated: 7/26/2004
Ada Hamosh - updated: 11/15/2002
Stylianos E. Antonarakis - updated: 6/21/2000
*FIELD* CD
Victor A. McKusick: 6/25/1986
*FIELD* ED
alopez: 07/31/2013
alopez: 7/26/2004
terry: 7/26/2004
alopez: 11/18/2002
terry: 11/15/2002
mgross: 6/21/2000
mgross: 9/17/1999
terry: 5/3/1999
alopez: 9/23/1998
dkim: 9/11/1998
carol: 3/20/1998
carol: 9/4/1992
supermim: 3/16/1992
carol: 5/22/1991
carol: 3/20/1991
supermim: 3/20/1990
supermim: 2/9/1990