Full text data of ANXA2
ANXA2
(ANX2, ANX2L4, CAL1H, LPC2D)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Annexin A2 (Annexin II; Annexin-2; Calpactin I heavy chain; Calpactin-1 heavy chain; Chromobindin-8; Lipocortin II; Placental anticoagulant protein IV; PAP-IV; Protein I; p36)
Annexin A2 (Annexin II; Annexin-2; Calpactin I heavy chain; Calpactin-1 heavy chain; Chromobindin-8; Lipocortin II; Placental anticoagulant protein IV; PAP-IV; Protein I; p36)
Comments
Isoform P07355-2 was detected.
Isoform P07355-2 was detected.
UniProt
P07355
ID ANXA2_HUMAN Reviewed; 339 AA.
AC P07355; Q567R4; Q6N0B3; Q8TBV2; Q96DD5; Q9UDH8;
DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 175.
DE RecName: Full=Annexin A2;
DE AltName: Full=Annexin II;
DE AltName: Full=Annexin-2;
DE AltName: Full=Calpactin I heavy chain;
DE AltName: Full=Calpactin-1 heavy chain;
DE AltName: Full=Chromobindin-8;
DE AltName: Full=Lipocortin II;
DE AltName: Full=Placental anticoagulant protein IV;
DE Short=PAP-IV;
DE AltName: Full=Protein I;
DE AltName: Full=p36;
GN Name=ANXA2; Synonyms=ANX2, ANX2L4, CAL1H, LPC2D;
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] (ISOFORM 1).
RC TISSUE=Placenta;
RX PubMed=3013422; DOI=10.1016/0092-8674(86)90736-1;
RA Huang K.-S., Wallner B.P., Mattaliano R.J., Tizard R., Burne C.,
RA Frey A., Hession C., McGray P., Sinclair L.K., Chow E.P.,
RA Browning J.L., Ramachandran K.L., Tang J., Smart J.E., Pepinsky R.B.;
RT "Two human 35 kd inhibitors of phospholipase A2 are related to
RT substrates of pp60v-src and of the epidermal growth factor
RT receptor/kinase.";
RL Cell 46:191-199(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=2174397; DOI=10.1016/0378-1119(90)90367-Z;
RA Spano F., Raugei G., Palla E., Colella C., Melli M.;
RT "Characterization of the human lipocortin-2-encoding multigene family:
RT its structure suggests the existence of a short amino acid unit
RT undergoing duplication.";
RL Gene 95:243-251(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Colon endothelium;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R.,
RA Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G.,
RA Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A.,
RA Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W.,
RA Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X.,
RA Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K.,
RA Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S.,
RA Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human
RT chromosome 15.";
RL Nature 440:671-675(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
RP LEU-98.
RC TISSUE=Brain, Colon, Pancreas, Prostate, Skin, Testis, and
RC Urinary bladder;
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 [7]
RP PROTEIN SEQUENCE OF 2-10; 38-47; 50-63; 69-77; 89-115; 153-169 AND
RP 213-220, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT SER-2, AND
RP MASS SPECTROMETRY.
RC TISSUE=Colon adenocarcinoma, and Osteosarcoma;
RA Bienvenut W.V., Murray L., Brunton V.G., Frame M.C., Bensaad K.,
RA Vousden K.H.;
RL Submitted (FEB-2008) to UniProtKB.
RN [8]
RP PROTEIN SEQUENCE OF 11-27; 49-62; 68-77; 120-135; 314-323 AND 329-339.
RX PubMed=1825830;
RA Jindal H.K., Chaney W.G., Anderson C.W., Davis R.G., Vishwanatha J.K.;
RT "The protein-tyrosine kinase substrate, calpactin I heavy chain (p36),
RT is part of the primer recognition protein complex that interacts with
RT DNA polymerase alpha.";
RL J. Biol. Chem. 266:5169-5176(1991).
RN [9]
RP PROTEIN SEQUENCE OF 15-40 AND 50-63.
RX PubMed=8110754; DOI=10.1021/bi00171a023;
RA Hyatt S.L., Liao L., Chapline C., Jaken S.;
RT "Identification and characterization of alpha-protein kinase C binding
RT proteins in normal and transformed REF52 cells.";
RL Biochemistry 33:1223-1228(1994).
RN [10]
RP PROTEIN SEQUENCE OF 18-37; 119-126; 172-191 AND 301-307, AND
RP INTERACTION WITH HCMV.
RC TISSUE=Umbilical vein endothelial cell;
RX PubMed=8117306; DOI=10.1006/bbrc.1994.1140;
RA Wright J.F., Kurosky A., Wasi S.;
RT "An endothelial cell-surface form of annexin II binds human
RT cytomegalovirus.";
RL Biochem. Biophys. Res. Commun. 198:983-989(1994).
RN [11]
RP PROTEIN SEQUENCE OF 234-241 AND 252-261.
RX PubMed=8449982; DOI=10.1083/jcb.120.6.1357;
RA Emans N., Gorvel J.P., Walter C., Gerke V., Kellner R., Griffiths G.,
RA Gruenberg J.;
RT "Annexin II is a major component of fusogenic endosomal vesicles.";
RL J. Cell Biol. 120:1357-1369(1993).
RN [12]
RP PHOSPHORYLATION AT SER-26.
RX PubMed=2946940;
RA Gould K.L., Woodgett J.R., Isacke C.M., Hunter T.;
RT "The protein-tyrosine kinase substrate p36 is also a substrate for
RT protein kinase C in vitro and in vivo.";
RL Mol. Cell. Biol. 6:2738-2744(1986).
RN [13]
RP PHOSPHORYLATION AT TYR-24, AND MUTAGENESIS OF TYR-24.
RX PubMed=15302870; DOI=10.1074/jbc.M408078200;
RA Deora A.B., Kreitzer G., Jacovina A.T., Hajjar K.A.;
RT "An annexin 2 phosphorylation switch mediates p11-dependent
RT translocation of annexin 2 to the cell surface.";
RL J. Biol. Chem. 279:43411-43418(2004).
RN [14]
RP ISGYLATION.
RX PubMed=16139798; DOI=10.1016/j.bbrc.2005.08.132;
RA Giannakopoulos N.V., Luo J.K., Papov V., Zou W., Lenschow D.J.,
RA Jacobs B.S., Borden E.C., Li J., Virgin H.W., Zhang D.E.;
RT "Proteomic identification of proteins conjugated to ISG15 in mouse and
RT human cells.";
RL Biochem. Biophys. Res. Commun. 336:496-506(2005).
RN [15]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H.,
RA Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R.,
RA Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E.,
RA Hunt D.F.;
RT "Proteomic and bioinformatic characterization of the biogenesis and
RT function of melanosomes.";
RL J. Proteome Res. 5:3135-3144(2006).
RN [16]
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 [17]
RP INTERACTION WITH COCH.
RX PubMed=21886777; DOI=10.1371/journal.pone.0023070;
RA Goel M., Sienkiewicz A.E., Picciani R., Lee R.K., Bhattacharya S.K.;
RT "Cochlin induced TREK-1 co-expression and annexin A2 secretion: role
RT in trabecular meshwork cell elongation and motility.";
RL PLoS ONE 6:E23070-E23070(2011).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
RX PubMed=8636985; DOI=10.1006/jmbi.1996.0205;
RA Burger A., Berendes R., Liemann S., Benz J., Hofmann A., Goettig P.,
RA Huber R., Gerke V., Tiel C., Roemisch J., Weber K.;
RT "The crystal structure and ion channel activity of human annexin II, a
RT peripheral membrane protein.";
RL J. Mol. Biol. 257:839-847(1996).
CC -!- FUNCTION: Calcium-regulated membrane-binding protein whose
CC affinity for calcium is greatly enhanced by anionic phospholipids.
CC It binds two calcium ions with high affinity. May be involved in
CC heat-stress response.
CC -!- SUBUNIT: Heterotetramer containing 2 light chains of S100A10/p11
CC and 2 heavy chains of ANXA2/p36. Interacts with ATP1B1 and DYSF
CC (By similarity). Interacts with human cytomegalovirus (HCMV).
CC Interacts with COCH.
CC -!- INTERACTION:
CC Q99IB8:- (xeno); NbExp=5; IntAct=EBI-352622, EBI-6931023;
CC P40692:MLH1; NbExp=7; IntAct=EBI-352622, EBI-744248;
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix, basement membrane. Melanosome. Note=In the lamina beneath
CC the plasma membrane. Identified by mass spectrometry in melanosome
CC fractions from stage I to stage IV. Translocated from the
CC cytoplasm to the cell surface through a Golgi-independent
CC mechanism.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P07355-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P07355-2; Sequence=VSP_038091;
CC -!- DOMAIN: A pair of annexin repeats may form one binding site for
CC calcium and phospholipid.
CC -!- PTM: Phosphorylation of Tyr-24 enhances heat stress-induced
CC translocation to the cell surface.
CC -!- PTM: ISGylated.
CC -!- MISCELLANEOUS: It may cross-link plasma membrane phospholipids
CC with actin and the cytoskeleton and be involved with exocytosis.
CC -!- SIMILARITY: Belongs to the annexin family.
CC -!- SIMILARITY: Contains 4 annexin repeats.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH66955.2; Type=Erroneous initiation;
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Red velvet - Issue 86
CC of September 2007;
CC URL="http://web.expasy.org/spotlight/back_issues/sptlt086.shtml";
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DR EMBL; D00017; BAA00013.1; -; mRNA.
DR EMBL; BT007432; AAP36100.1; -; mRNA.
DR EMBL; BX640598; CAE45704.1; -; mRNA.
DR EMBL; AC087385; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC001388; AAH01388.1; -; mRNA.
DR EMBL; BC009564; AAH09564.1; -; mRNA.
DR EMBL; BC015834; AAH15834.1; -; mRNA.
DR EMBL; BC016774; AAH16774.1; -; mRNA.
DR EMBL; BC021114; AAH21114.1; -; mRNA.
DR EMBL; BC023990; AAH23990.1; -; mRNA.
DR EMBL; BC052558; AAH52558.1; -; mRNA.
DR EMBL; BC052567; AAH52567.1; -; mRNA.
DR EMBL; BC066955; AAH66955.2; ALT_INIT; mRNA.
DR EMBL; BC068065; AAH68065.1; -; mRNA.
DR EMBL; BC093056; AAH93056.1; -; mRNA.
DR PIR; A23942; LUHU36.
DR RefSeq; NP_001002857.1; NM_001002857.1.
DR RefSeq; NP_001002858.1; NM_001002858.2.
DR RefSeq; NP_001129487.1; NM_001136015.2.
DR RefSeq; NP_004030.1; NM_004039.2.
DR UniGene; Hs.511605; -.
DR PDB; 1W7B; X-ray; 1.52 A; A=1-339.
DR PDB; 1XJL; X-ray; 2.59 A; A/B=21-338.
DR PDB; 2HYU; X-ray; 1.86 A; A=32-338.
DR PDB; 2HYV; X-ray; 1.42 A; A=32-338.
DR PDB; 2HYW; X-ray; 2.10 A; A/B=32-338.
DR PDB; 4DRW; X-ray; 3.50 A; A/B/C/D=2-16.
DR PDB; 4HRH; X-ray; 3.00 A; A/B=2-16.
DR PDBsum; 1W7B; -.
DR PDBsum; 1XJL; -.
DR PDBsum; 2HYU; -.
DR PDBsum; 2HYV; -.
DR PDBsum; 2HYW; -.
DR PDBsum; 4DRW; -.
DR PDBsum; 4HRH; -.
DR ProteinModelPortal; P07355; -.
DR SMR; P07355; 32-339.
DR IntAct; P07355; 29.
DR MINT; MINT-1213203; -.
DR STRING; 9606.ENSP00000346032; -.
DR BindingDB; P07355; -.
DR ChEMBL; CHEMBL2111435; -.
DR DrugBank; DB00009; Alteplase.
DR DrugBank; DB00029; Anistreplase.
DR DrugBank; DB00031; Tenecteplase.
DR PhosphoSite; P07355; -.
DR DMDM; 113950; -.
DR DOSAC-COBS-2DPAGE; P07355; -.
DR REPRODUCTION-2DPAGE; IPI00455315; -.
DR REPRODUCTION-2DPAGE; P07355; -.
DR UCD-2DPAGE; P07355; -.
DR PaxDb; P07355; -.
DR PRIDE; P07355; -.
DR DNASU; 302; -.
DR Ensembl; ENST00000332680; ENSP00000346032; ENSG00000182718.
DR Ensembl; ENST00000396024; ENSP00000379342; ENSG00000182718.
DR Ensembl; ENST00000421017; ENSP00000411352; ENSG00000182718.
DR Ensembl; ENST00000451270; ENSP00000387545; ENSG00000182718.
DR GeneID; 302; -.
DR KEGG; hsa:302; -.
DR UCSC; uc002agk.3; human.
DR CTD; 302; -.
DR GeneCards; GC15M060639; -.
DR HGNC; HGNC:537; ANXA2.
DR HPA; CAB004311; -.
DR MIM; 151740; gene.
DR neXtProt; NX_P07355; -.
DR PharmGKB; PA24827; -.
DR eggNOG; NOG259189; -.
DR HOGENOM; HOG000158803; -.
DR HOVERGEN; HBG061815; -.
DR InParanoid; P07355; -.
DR KO; K17092; -.
DR OMA; FIQQDTK; -.
DR OrthoDB; EOG74XS72; -.
DR ChiTaRS; ANXA2; human.
DR EvolutionaryTrace; P07355; -.
DR GeneWiki; Annexin_A2; -.
DR GenomeRNAi; 302; -.
DR NextBio; 1217; -.
DR PRO; PR:P07355; -.
DR ArrayExpress; P07355; -.
DR Bgee; P07355; -.
DR CleanEx; HS_ANXA2; -.
DR Genevestigator; P07355; -.
DR GO; GO:0005604; C:basement membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005769; C:early endosome; IEA:Ensembl.
DR GO; GO:0070062; C:extracellular vesicular exosome; IDA:UniProtKB.
DR GO; GO:0019897; C:extrinsic to plasma membrane; IEA:Ensembl.
DR GO; GO:0005811; C:lipid particle; IDA:UniProtKB.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0030496; C:midbody; IDA:UniProtKB.
DR GO; GO:0035749; C:myelin sheath adaxonal region; IEA:Ensembl.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0043234; C:protein complex; IEA:Ensembl.
DR GO; GO:0042383; C:sarcolemma; IEA:Ensembl.
DR GO; GO:0043220; C:Schmidt-Lanterman incisure; IEA:Ensembl.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0005544; F:calcium-dependent phospholipid binding; IDA:UniProtKB.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IEA:Ensembl.
DR GO; GO:0004859; F:phospholipase inhibitor activity; IEA:InterPro.
DR GO; GO:0001525; P:angiogenesis; IEP:UniProtKB.
DR GO; GO:0007589; P:body fluid secretion; IEA:Ensembl.
DR GO; GO:0071229; P:cellular response to acid; IEA:Ensembl.
DR GO; GO:0030199; P:collagen fibril organization; IEA:Ensembl.
DR GO; GO:0042730; P:fibrinolysis; IEA:Ensembl.
DR GO; GO:0051099; P:positive regulation of binding; IEA:Ensembl.
DR GO; GO:0031340; P:positive regulation of vesicle fusion; IDA: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; IPR002389; AnnexinII.
DR PANTHER; PTHR10502:SF18; PTHR10502:SF18; 1.
DR Pfam; PF00191; Annexin; 4.
DR PRINTS; PR00196; ANNEXIN.
DR PRINTS; PR00198; ANNEXINII.
DR SMART; SM00335; ANX; 4.
DR PROSITE; PS00223; ANNEXIN; 4.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Annexin;
KW Basement membrane; Calcium; Calcium/phospholipid-binding;
KW Complete proteome; Direct protein sequencing; Extracellular matrix;
KW Phosphoprotein; Polymorphism; Reference proteome; Repeat; Secreted;
KW Ubl conjugation.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 339 Annexin A2.
FT /FTId=PRO_0000067470.
FT REPEAT 42 102 Annexin 1.
FT REPEAT 114 174 Annexin 2.
FT REPEAT 199 259 Annexin 3.
FT REPEAT 274 334 Annexin 4.
FT REGION 2 24 S100A10-binding site (Potential).
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 24 24 Phosphotyrosine; by SRC.
FT MOD_RES 26 26 Phosphoserine; by PKC.
FT MOD_RES 199 199 Phosphotyrosine (By similarity).
FT VAR_SEQ 1 1 M -> MGRQLAGCGDAGKKASFKM (in isoform 2).
FT /FTId=VSP_038091.
FT VARIANT 98 98 V -> L (in dbSNP:rs17845226).
FT /FTId=VAR_012982.
FT MUTAGEN 24 24 Y->A: Abolishes heat stress-induced cell
FT surface localization.
FT CONFLICT 29 29 A -> P (in Ref. 9; AA sequence).
FT CONFLICT 166 166 D -> G (in Ref. 4; CAE45704).
FT CONFLICT 293 293 V -> A (in Ref. 6; AAH23990).
FT HELIX 3 9
FT HELIX 35 47
FT HELIX 53 60
FT HELIX 65 79
FT HELIX 83 90
FT HELIX 93 103
FT HELIX 106 117
FT STRAND 120 122
FT HELIX 125 134
FT HELIX 137 151
FT HELIX 155 161
FT HELIX 165 175
FT HELIX 188 200
FT TURN 201 204
FT STRAND 205 207
FT HELIX 210 219
FT HELIX 222 232
FT TURN 233 235
FT HELIX 240 247
FT HELIX 250 264
FT HELIX 266 278
FT STRAND 279 282
FT HELIX 285 295
FT TURN 296 298
FT HELIX 300 311
FT HELIX 315 322
FT HELIX 325 335
SQ SEQUENCE 339 AA; 38604 MW; 5126E1337A0CBEA1 CRC64;
MSTVHEILCK LSLEGDHSTP PSAYGSVKAY TNFDAERDAL NIETAIKTKG VDEVTIVNIL
TNRSNAQRQD IAFAYQRRTK KELASALKSA LSGHLETVIL GLLKTPAQYD ASELKASMKG
LGTDEDSLIE IICSRTNQEL QEINRVYKEM YKTDLEKDII SDTSGDFRKL MVALAKGRRA
EDGSVIDYEL IDQDARDLYD AGVKRKGTDV PKWISIMTER SVPHLQKVFD RYKSYSPYDM
LESIRKEVKG DLENAFLNLV QCIQNKPLYF ADRLYDSMKG KGTRDKVLIR IMVSRSEVDM
LKIRSEFKRK YGKSLYYYIQ QDTKGDYQKA LLYLCGGDD
//
ID ANXA2_HUMAN Reviewed; 339 AA.
AC P07355; Q567R4; Q6N0B3; Q8TBV2; Q96DD5; Q9UDH8;
DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 175.
DE RecName: Full=Annexin A2;
DE AltName: Full=Annexin II;
DE AltName: Full=Annexin-2;
DE AltName: Full=Calpactin I heavy chain;
DE AltName: Full=Calpactin-1 heavy chain;
DE AltName: Full=Chromobindin-8;
DE AltName: Full=Lipocortin II;
DE AltName: Full=Placental anticoagulant protein IV;
DE Short=PAP-IV;
DE AltName: Full=Protein I;
DE AltName: Full=p36;
GN Name=ANXA2; Synonyms=ANX2, ANX2L4, CAL1H, LPC2D;
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] (ISOFORM 1).
RC TISSUE=Placenta;
RX PubMed=3013422; DOI=10.1016/0092-8674(86)90736-1;
RA Huang K.-S., Wallner B.P., Mattaliano R.J., Tizard R., Burne C.,
RA Frey A., Hession C., McGray P., Sinclair L.K., Chow E.P.,
RA Browning J.L., Ramachandran K.L., Tang J., Smart J.E., Pepinsky R.B.;
RT "Two human 35 kd inhibitors of phospholipase A2 are related to
RT substrates of pp60v-src and of the epidermal growth factor
RT receptor/kinase.";
RL Cell 46:191-199(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=2174397; DOI=10.1016/0378-1119(90)90367-Z;
RA Spano F., Raugei G., Palla E., Colella C., Melli M.;
RT "Characterization of the human lipocortin-2-encoding multigene family:
RT its structure suggests the existence of a short amino acid unit
RT undergoing duplication.";
RL Gene 95:243-251(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Colon endothelium;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R.,
RA Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G.,
RA Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A.,
RA Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W.,
RA Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X.,
RA Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K.,
RA Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S.,
RA Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human
RT chromosome 15.";
RL Nature 440:671-675(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
RP LEU-98.
RC TISSUE=Brain, Colon, Pancreas, Prostate, Skin, Testis, and
RC Urinary bladder;
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 [7]
RP PROTEIN SEQUENCE OF 2-10; 38-47; 50-63; 69-77; 89-115; 153-169 AND
RP 213-220, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT SER-2, AND
RP MASS SPECTROMETRY.
RC TISSUE=Colon adenocarcinoma, and Osteosarcoma;
RA Bienvenut W.V., Murray L., Brunton V.G., Frame M.C., Bensaad K.,
RA Vousden K.H.;
RL Submitted (FEB-2008) to UniProtKB.
RN [8]
RP PROTEIN SEQUENCE OF 11-27; 49-62; 68-77; 120-135; 314-323 AND 329-339.
RX PubMed=1825830;
RA Jindal H.K., Chaney W.G., Anderson C.W., Davis R.G., Vishwanatha J.K.;
RT "The protein-tyrosine kinase substrate, calpactin I heavy chain (p36),
RT is part of the primer recognition protein complex that interacts with
RT DNA polymerase alpha.";
RL J. Biol. Chem. 266:5169-5176(1991).
RN [9]
RP PROTEIN SEQUENCE OF 15-40 AND 50-63.
RX PubMed=8110754; DOI=10.1021/bi00171a023;
RA Hyatt S.L., Liao L., Chapline C., Jaken S.;
RT "Identification and characterization of alpha-protein kinase C binding
RT proteins in normal and transformed REF52 cells.";
RL Biochemistry 33:1223-1228(1994).
RN [10]
RP PROTEIN SEQUENCE OF 18-37; 119-126; 172-191 AND 301-307, AND
RP INTERACTION WITH HCMV.
RC TISSUE=Umbilical vein endothelial cell;
RX PubMed=8117306; DOI=10.1006/bbrc.1994.1140;
RA Wright J.F., Kurosky A., Wasi S.;
RT "An endothelial cell-surface form of annexin II binds human
RT cytomegalovirus.";
RL Biochem. Biophys. Res. Commun. 198:983-989(1994).
RN [11]
RP PROTEIN SEQUENCE OF 234-241 AND 252-261.
RX PubMed=8449982; DOI=10.1083/jcb.120.6.1357;
RA Emans N., Gorvel J.P., Walter C., Gerke V., Kellner R., Griffiths G.,
RA Gruenberg J.;
RT "Annexin II is a major component of fusogenic endosomal vesicles.";
RL J. Cell Biol. 120:1357-1369(1993).
RN [12]
RP PHOSPHORYLATION AT SER-26.
RX PubMed=2946940;
RA Gould K.L., Woodgett J.R., Isacke C.M., Hunter T.;
RT "The protein-tyrosine kinase substrate p36 is also a substrate for
RT protein kinase C in vitro and in vivo.";
RL Mol. Cell. Biol. 6:2738-2744(1986).
RN [13]
RP PHOSPHORYLATION AT TYR-24, AND MUTAGENESIS OF TYR-24.
RX PubMed=15302870; DOI=10.1074/jbc.M408078200;
RA Deora A.B., Kreitzer G., Jacovina A.T., Hajjar K.A.;
RT "An annexin 2 phosphorylation switch mediates p11-dependent
RT translocation of annexin 2 to the cell surface.";
RL J. Biol. Chem. 279:43411-43418(2004).
RN [14]
RP ISGYLATION.
RX PubMed=16139798; DOI=10.1016/j.bbrc.2005.08.132;
RA Giannakopoulos N.V., Luo J.K., Papov V., Zou W., Lenschow D.J.,
RA Jacobs B.S., Borden E.C., Li J., Virgin H.W., Zhang D.E.;
RT "Proteomic identification of proteins conjugated to ISG15 in mouse and
RT human cells.";
RL Biochem. Biophys. Res. Commun. 336:496-506(2005).
RN [15]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H.,
RA Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R.,
RA Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E.,
RA Hunt D.F.;
RT "Proteomic and bioinformatic characterization of the biogenesis and
RT function of melanosomes.";
RL J. Proteome Res. 5:3135-3144(2006).
RN [16]
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 [17]
RP INTERACTION WITH COCH.
RX PubMed=21886777; DOI=10.1371/journal.pone.0023070;
RA Goel M., Sienkiewicz A.E., Picciani R., Lee R.K., Bhattacharya S.K.;
RT "Cochlin induced TREK-1 co-expression and annexin A2 secretion: role
RT in trabecular meshwork cell elongation and motility.";
RL PLoS ONE 6:E23070-E23070(2011).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
RX PubMed=8636985; DOI=10.1006/jmbi.1996.0205;
RA Burger A., Berendes R., Liemann S., Benz J., Hofmann A., Goettig P.,
RA Huber R., Gerke V., Tiel C., Roemisch J., Weber K.;
RT "The crystal structure and ion channel activity of human annexin II, a
RT peripheral membrane protein.";
RL J. Mol. Biol. 257:839-847(1996).
CC -!- FUNCTION: Calcium-regulated membrane-binding protein whose
CC affinity for calcium is greatly enhanced by anionic phospholipids.
CC It binds two calcium ions with high affinity. May be involved in
CC heat-stress response.
CC -!- SUBUNIT: Heterotetramer containing 2 light chains of S100A10/p11
CC and 2 heavy chains of ANXA2/p36. Interacts with ATP1B1 and DYSF
CC (By similarity). Interacts with human cytomegalovirus (HCMV).
CC Interacts with COCH.
CC -!- INTERACTION:
CC Q99IB8:- (xeno); NbExp=5; IntAct=EBI-352622, EBI-6931023;
CC P40692:MLH1; NbExp=7; IntAct=EBI-352622, EBI-744248;
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix, basement membrane. Melanosome. Note=In the lamina beneath
CC the plasma membrane. Identified by mass spectrometry in melanosome
CC fractions from stage I to stage IV. Translocated from the
CC cytoplasm to the cell surface through a Golgi-independent
CC mechanism.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P07355-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P07355-2; Sequence=VSP_038091;
CC -!- DOMAIN: A pair of annexin repeats may form one binding site for
CC calcium and phospholipid.
CC -!- PTM: Phosphorylation of Tyr-24 enhances heat stress-induced
CC translocation to the cell surface.
CC -!- PTM: ISGylated.
CC -!- MISCELLANEOUS: It may cross-link plasma membrane phospholipids
CC with actin and the cytoskeleton and be involved with exocytosis.
CC -!- SIMILARITY: Belongs to the annexin family.
CC -!- SIMILARITY: Contains 4 annexin repeats.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH66955.2; Type=Erroneous initiation;
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Red velvet - Issue 86
CC of September 2007;
CC URL="http://web.expasy.org/spotlight/back_issues/sptlt086.shtml";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
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DR EMBL; D00017; BAA00013.1; -; mRNA.
DR EMBL; BT007432; AAP36100.1; -; mRNA.
DR EMBL; BX640598; CAE45704.1; -; mRNA.
DR EMBL; AC087385; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC001388; AAH01388.1; -; mRNA.
DR EMBL; BC009564; AAH09564.1; -; mRNA.
DR EMBL; BC015834; AAH15834.1; -; mRNA.
DR EMBL; BC016774; AAH16774.1; -; mRNA.
DR EMBL; BC021114; AAH21114.1; -; mRNA.
DR EMBL; BC023990; AAH23990.1; -; mRNA.
DR EMBL; BC052558; AAH52558.1; -; mRNA.
DR EMBL; BC052567; AAH52567.1; -; mRNA.
DR EMBL; BC066955; AAH66955.2; ALT_INIT; mRNA.
DR EMBL; BC068065; AAH68065.1; -; mRNA.
DR EMBL; BC093056; AAH93056.1; -; mRNA.
DR PIR; A23942; LUHU36.
DR RefSeq; NP_001002857.1; NM_001002857.1.
DR RefSeq; NP_001002858.1; NM_001002858.2.
DR RefSeq; NP_001129487.1; NM_001136015.2.
DR RefSeq; NP_004030.1; NM_004039.2.
DR UniGene; Hs.511605; -.
DR PDB; 1W7B; X-ray; 1.52 A; A=1-339.
DR PDB; 1XJL; X-ray; 2.59 A; A/B=21-338.
DR PDB; 2HYU; X-ray; 1.86 A; A=32-338.
DR PDB; 2HYV; X-ray; 1.42 A; A=32-338.
DR PDB; 2HYW; X-ray; 2.10 A; A/B=32-338.
DR PDB; 4DRW; X-ray; 3.50 A; A/B/C/D=2-16.
DR PDB; 4HRH; X-ray; 3.00 A; A/B=2-16.
DR PDBsum; 1W7B; -.
DR PDBsum; 1XJL; -.
DR PDBsum; 2HYU; -.
DR PDBsum; 2HYV; -.
DR PDBsum; 2HYW; -.
DR PDBsum; 4DRW; -.
DR PDBsum; 4HRH; -.
DR ProteinModelPortal; P07355; -.
DR SMR; P07355; 32-339.
DR IntAct; P07355; 29.
DR MINT; MINT-1213203; -.
DR STRING; 9606.ENSP00000346032; -.
DR BindingDB; P07355; -.
DR ChEMBL; CHEMBL2111435; -.
DR DrugBank; DB00009; Alteplase.
DR DrugBank; DB00029; Anistreplase.
DR DrugBank; DB00031; Tenecteplase.
DR PhosphoSite; P07355; -.
DR DMDM; 113950; -.
DR DOSAC-COBS-2DPAGE; P07355; -.
DR REPRODUCTION-2DPAGE; IPI00455315; -.
DR REPRODUCTION-2DPAGE; P07355; -.
DR UCD-2DPAGE; P07355; -.
DR PaxDb; P07355; -.
DR PRIDE; P07355; -.
DR DNASU; 302; -.
DR Ensembl; ENST00000332680; ENSP00000346032; ENSG00000182718.
DR Ensembl; ENST00000396024; ENSP00000379342; ENSG00000182718.
DR Ensembl; ENST00000421017; ENSP00000411352; ENSG00000182718.
DR Ensembl; ENST00000451270; ENSP00000387545; ENSG00000182718.
DR GeneID; 302; -.
DR KEGG; hsa:302; -.
DR UCSC; uc002agk.3; human.
DR CTD; 302; -.
DR GeneCards; GC15M060639; -.
DR HGNC; HGNC:537; ANXA2.
DR HPA; CAB004311; -.
DR MIM; 151740; gene.
DR neXtProt; NX_P07355; -.
DR PharmGKB; PA24827; -.
DR eggNOG; NOG259189; -.
DR HOGENOM; HOG000158803; -.
DR HOVERGEN; HBG061815; -.
DR InParanoid; P07355; -.
DR KO; K17092; -.
DR OMA; FIQQDTK; -.
DR OrthoDB; EOG74XS72; -.
DR ChiTaRS; ANXA2; human.
DR EvolutionaryTrace; P07355; -.
DR GeneWiki; Annexin_A2; -.
DR GenomeRNAi; 302; -.
DR NextBio; 1217; -.
DR PRO; PR:P07355; -.
DR ArrayExpress; P07355; -.
DR Bgee; P07355; -.
DR CleanEx; HS_ANXA2; -.
DR Genevestigator; P07355; -.
DR GO; GO:0005604; C:basement membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005769; C:early endosome; IEA:Ensembl.
DR GO; GO:0070062; C:extracellular vesicular exosome; IDA:UniProtKB.
DR GO; GO:0019897; C:extrinsic to plasma membrane; IEA:Ensembl.
DR GO; GO:0005811; C:lipid particle; IDA:UniProtKB.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0030496; C:midbody; IDA:UniProtKB.
DR GO; GO:0035749; C:myelin sheath adaxonal region; IEA:Ensembl.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0043234; C:protein complex; IEA:Ensembl.
DR GO; GO:0042383; C:sarcolemma; IEA:Ensembl.
DR GO; GO:0043220; C:Schmidt-Lanterman incisure; IEA:Ensembl.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0005544; F:calcium-dependent phospholipid binding; IDA:UniProtKB.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IEA:Ensembl.
DR GO; GO:0004859; F:phospholipase inhibitor activity; IEA:InterPro.
DR GO; GO:0001525; P:angiogenesis; IEP:UniProtKB.
DR GO; GO:0007589; P:body fluid secretion; IEA:Ensembl.
DR GO; GO:0071229; P:cellular response to acid; IEA:Ensembl.
DR GO; GO:0030199; P:collagen fibril organization; IEA:Ensembl.
DR GO; GO:0042730; P:fibrinolysis; IEA:Ensembl.
DR GO; GO:0051099; P:positive regulation of binding; IEA:Ensembl.
DR GO; GO:0031340; P:positive regulation of vesicle fusion; IDA: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; IPR002389; AnnexinII.
DR PANTHER; PTHR10502:SF18; PTHR10502:SF18; 1.
DR Pfam; PF00191; Annexin; 4.
DR PRINTS; PR00196; ANNEXIN.
DR PRINTS; PR00198; ANNEXINII.
DR SMART; SM00335; ANX; 4.
DR PROSITE; PS00223; ANNEXIN; 4.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Annexin;
KW Basement membrane; Calcium; Calcium/phospholipid-binding;
KW Complete proteome; Direct protein sequencing; Extracellular matrix;
KW Phosphoprotein; Polymorphism; Reference proteome; Repeat; Secreted;
KW Ubl conjugation.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 339 Annexin A2.
FT /FTId=PRO_0000067470.
FT REPEAT 42 102 Annexin 1.
FT REPEAT 114 174 Annexin 2.
FT REPEAT 199 259 Annexin 3.
FT REPEAT 274 334 Annexin 4.
FT REGION 2 24 S100A10-binding site (Potential).
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 24 24 Phosphotyrosine; by SRC.
FT MOD_RES 26 26 Phosphoserine; by PKC.
FT MOD_RES 199 199 Phosphotyrosine (By similarity).
FT VAR_SEQ 1 1 M -> MGRQLAGCGDAGKKASFKM (in isoform 2).
FT /FTId=VSP_038091.
FT VARIANT 98 98 V -> L (in dbSNP:rs17845226).
FT /FTId=VAR_012982.
FT MUTAGEN 24 24 Y->A: Abolishes heat stress-induced cell
FT surface localization.
FT CONFLICT 29 29 A -> P (in Ref. 9; AA sequence).
FT CONFLICT 166 166 D -> G (in Ref. 4; CAE45704).
FT CONFLICT 293 293 V -> A (in Ref. 6; AAH23990).
FT HELIX 3 9
FT HELIX 35 47
FT HELIX 53 60
FT HELIX 65 79
FT HELIX 83 90
FT HELIX 93 103
FT HELIX 106 117
FT STRAND 120 122
FT HELIX 125 134
FT HELIX 137 151
FT HELIX 155 161
FT HELIX 165 175
FT HELIX 188 200
FT TURN 201 204
FT STRAND 205 207
FT HELIX 210 219
FT HELIX 222 232
FT TURN 233 235
FT HELIX 240 247
FT HELIX 250 264
FT HELIX 266 278
FT STRAND 279 282
FT HELIX 285 295
FT TURN 296 298
FT HELIX 300 311
FT HELIX 315 322
FT HELIX 325 335
SQ SEQUENCE 339 AA; 38604 MW; 5126E1337A0CBEA1 CRC64;
MSTVHEILCK LSLEGDHSTP PSAYGSVKAY TNFDAERDAL NIETAIKTKG VDEVTIVNIL
TNRSNAQRQD IAFAYQRRTK KELASALKSA LSGHLETVIL GLLKTPAQYD ASELKASMKG
LGTDEDSLIE IICSRTNQEL QEINRVYKEM YKTDLEKDII SDTSGDFRKL MVALAKGRRA
EDGSVIDYEL IDQDARDLYD AGVKRKGTDV PKWISIMTER SVPHLQKVFD RYKSYSPYDM
LESIRKEVKG DLENAFLNLV QCIQNKPLYF ADRLYDSMKG KGTRDKVLIR IMVSRSEVDM
LKIRSEFKRK YGKSLYYYIQ QDTKGDYQKA LLYLCGGDD
//
MIM
151740
*RECORD*
*FIELD* NO
151740
*FIELD* TI
*151740 ANNEXIN A2; ANXA2
;;ANNEXIN II; ANX2;;
ANNEXIN II, HEAVY CHAIN;;
LIPOCORTIN II; LPC2; LIP2
read moreANNEXIN II PSEUDOGENE 1, INCLUDED; ANX2P1, INCLUDED;;
ANX2P2, INCLUDED;;
ANX2P3, INCLUDED
*FIELD* TX
CLONING
Huang et al. (1986) purified 2 phospholipase A2 (603603) inhibitors from
placenta, ANXA1 (151690) and ANXA2, which they called lipocortin I and
II, respectively. Western blot analysis detected ANXA2 at an apparent
molecular mass of 35 kD in placenta and in all human and mammalian cell
lines tested. Highest expression was found in epithelial cell lines. By
screening placenta and monocytic cell line cDNA libraries using a
nucleotide probe based on tryptic fragments, Huang et al. (1986) cloned
ANXA2. ANXA2 and ANXA1 share about 50% amino acid homology, with highest
homology in the central region, which in ANXA1 is important for
phospholipase A2 inhibitory activity. Both proteins have a primary
structure built from 4 repeats of a single unit, contain an N-terminal
tyrosine phosphorylation site, and lack a signal sequence.
Annexin II, a major cellular substrate of the tyrosine kinase encoded by
the SRC oncogene (190090), belongs to the annexin family of
Ca(2+)-dependent phospholipid- and membrane-binding proteins. By
screening a cDNA expression library generated from highly purified human
osteoclast-like multinuclear cells (MNC) formed in long-term bone marrow
cultures, Takahashi et al. (1994) identified a candidate clone that
stimulated MNC formation. Sequence analysis showed that this cDNA
encoded annexin II. Further studies yielded results suggesting that ANX2
is an autocrine factor that enhances osteoclast formation and bone
resorption, a previously unknown function for this molecule.
GENE FUNCTION
Formation of the apical surface and lumen is a fundamental step in
epithelial organ development. Martin-Belmonte et al. (2007) showed that
Pten (601728) localized to the apical plasma membrane during epithelial
morphogenesis to mediate enrichment of phosphatidylinositol
4,5-bisphosphate (PtdIns(4,5)P2) at this domain during cyst development
in a 3-dimensional Madin-Darby canine kidney cell system. Ectopic
PtdIns(4,5)P2 at the basolateral surface caused apical proteins to
relocalize to the basolateral surface. Anx2 bound PtdIns(4,5)P2 and was
recruited to the apical surface. Anx2 bound Cdc42 (116952) and recruited
it to the apical surface, and Cdc42 in turn recruited the Par6
(607484)/atypical protein kinase C (aPKC; see 176982) complex to the
apical surface. Loss of function of Pten, Anx2, Cdc42, or aPKC prevented
normal development of the apical surface and lumen. Martin-Belmonte et
al. (2007) concluded that PTEN, PtdIns(4,5)P2, ANX2, CDC42, and aPKC
control apical plasma membrane and lumen formation.
GENE STRUCTURE
Spano et al. (1990) isolated and characterized human genomic clones of
the gene encoding lipocortin II (LIP2) and of 3 pseudogenes. The LIP2
gene is at least 40 kb long and consists of 13 exons. The 3 LIP2
pseudogenes show typical features of retroposons.
MAPPING
Spano et al. (1990) reported experiments which, together with the data
published by Huebner et al. (1988), led them to conclude that the LIP2
gene is located on chromosome 15. Richard et al. (1994) presented an
integration of the physical, expression, and genetic maps of human
chromosome 15. They placed the ANXA2 gene in their region IV, i.e.,
15q21-q22, thus confirming the previous localization.
- Pseudogenes
By use of cDNAs in somatic cell hybrid analysis and in situ
hybridization, Huebner et al. (1987, 1988) mapped the LPC2A (LIP2P1)
locus to 4q21-q31. Spano et al. (1990) mapped the 3 LIP2 pseudogenes to
chromosomes 4 (ANX2P1), 9 (ANX2P2) and 10 (ANX2P3). The coexistence on
chromosome 9 of the LIP1 gene (151690) and a LIP pseudogene was
considered fortuitous.
By means of a lipocortin cDNA in somatic cell hybrid analysis and in
situ chromosome hybridization, Huebner et al. (1987, 1988) mapped LPC2B
(ANX2P2) to chromosome 9. Thus, LPC1 and LPC2B are syntenic. LPC2B is
located proximal to ABL (189980). Calpactin I is a synonym for
lipocortin II.
Huebner et al. (1987, 1988) mapped the LPC2C (ANX2P3) gene to 10q21-q22.
ANIMAL MODEL
Ling et al. (2004) generated Anxa2-null mice that displayed deposition
of fibrin in the microvasculature and incomplete clearance of
injury-induced arterial thrombi. The null mice demonstrated normal lysis
of fibrin-containing plasma clots, but tissue plasminogen activator
(tPA; 173370)-dependent plasmin generation at the endothelial cell
surface was markedly deficient. Directed migration of Anxa2-null
endothelial cells through fibrin and collagen lattices in vitro was also
reduced, and a peptide mimicking ANXA2 sequences necessary for tPA
binding blocked endothelial cell invasion of Matrigel implants in
wildtype mice. In addition, Anxa2-null mice displayed markedly
diminished neovascularization of fibroblast growth factor (see
131220)-stimulated cornea and of oxygen-primed neonatal retina.
Capillary sprouting from Anxa2-deficient aortic ring explants was
markedly reduced in association with severe impairment of activation of
metalloproteinase-9 (MMP9; 120361) and -13 (MMP13; 600108). Ling et al.
(2004) concluded that ANXA2 is a regulator of cell surface plasmin
generation and that impaired endothelial cell fibrinolytic activity
constitutes a barrier to effective neoangiogenesis.
*FIELD* RF
1. Huang, K.-S.; Wallner, B. P.; Mattaliano, R. J.; Tizard, R.; Burne,
C.; Frey, A.; Hession, C.; McGray, P.; Sinclair, L. K.; Chow, E. P.;
Browning, J. L.; Ramachandran, K. L.; Tang, J.; Smart, J. E.; Pepinsky,
R. B.: Two human 35 kd inhibitors of phospholipase A2 are related
to substrates of pp60(v-src) and of the epidermal growth factor receptor/kinase. Cell 46:
191-199, 1986.
2. 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.
3. 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.
4. Ling, Q.; Jacovina, A. T.; Deora, A.; Febbraio, M.; Simantov, R.;
Silverstein, R. L.; Hempstead, B.; Mark, W. H.; Hajjar, K. A.: Annexin
II regulates fibrin homeostasis and neoangiogenesis in vivo. J. Clin.
Invest. 113: 38-48, 2004.
5. Martin-Belmonte, F.; Gassama, A.; Datta, A.; Yu, W.; Rescher, U.;
Gerke, V.; Mostov, K.: PTEN-mediated apical segregation of phosphoinositides
controls epithelial morphogenesis through Cdc42. Cell 128: 383-397,
2007.
6. Richard, I.; Broux, O.; Chiannilkulchai, N.; Fougerousse, F.; Allamand,
V.; Bourg, N.; Brenguier, L.; Devaud, C.; Pasturaud, P.; Roudaut,
C.; Lorenzo, F.; Sebastiani-Kabatchis, C.; Schultz, R. A.; Polymeropoulos,
M. H.; Gyapay, G.; Auffray, C.; Beckmann, J. S.: Regional localization
of human chromosome 15 loci. Genomics 23: 619-627, 1994.
7. Spano, F.; Raugei, G.; Palla, E.; Colella, C.; Melli, M.: Characterization
of the human lipocortin-2-encoding multigene family: its structure
suggests the existence of a short amino acid unit undergoing duplication. Gene 95:
243-251, 1990.
8. Takahashi, S.; Reddy, S. V.; Chirgwin, J. M.; Devlin, R.; Haipek,
C.; Anderson, J.; Roodman, G. D.: Cloning and identification of annexin
II as an autocrine/paracrine factor that increases osteoclast formation
and bone resorption. J. Biol. Chem. 269: 28696-28701, 1994.
*FIELD* CN
Matthew B. Gross - updated: 5/11/2010
Marla J. F. O'Neill - updated: 3/30/2004
Patricia A. Hartz - updated: 3/22/2004
*FIELD* CD
Victor A. McKusick: 9/23/1987
*FIELD* ED
wwang: 05/17/2010
mgross: 5/11/2010
terry: 3/16/2005
tkritzer: 3/30/2004
mgross: 3/30/2004
terry: 3/22/2004
carol: 8/4/2003
alopez: 6/5/2002
mgross: 9/17/1999
alopez: 5/13/1999
terry: 7/31/1998
dkim: 7/24/1998
mark: 1/20/1997
mark: 1/18/1997
carol: 1/30/1995
carol: 11/12/1993
carol: 7/24/1992
supermim: 3/16/1992
carol: 6/6/1991
carol: 3/19/1991
*RECORD*
*FIELD* NO
151740
*FIELD* TI
*151740 ANNEXIN A2; ANXA2
;;ANNEXIN II; ANX2;;
ANNEXIN II, HEAVY CHAIN;;
LIPOCORTIN II; LPC2; LIP2
read moreANNEXIN II PSEUDOGENE 1, INCLUDED; ANX2P1, INCLUDED;;
ANX2P2, INCLUDED;;
ANX2P3, INCLUDED
*FIELD* TX
CLONING
Huang et al. (1986) purified 2 phospholipase A2 (603603) inhibitors from
placenta, ANXA1 (151690) and ANXA2, which they called lipocortin I and
II, respectively. Western blot analysis detected ANXA2 at an apparent
molecular mass of 35 kD in placenta and in all human and mammalian cell
lines tested. Highest expression was found in epithelial cell lines. By
screening placenta and monocytic cell line cDNA libraries using a
nucleotide probe based on tryptic fragments, Huang et al. (1986) cloned
ANXA2. ANXA2 and ANXA1 share about 50% amino acid homology, with highest
homology in the central region, which in ANXA1 is important for
phospholipase A2 inhibitory activity. Both proteins have a primary
structure built from 4 repeats of a single unit, contain an N-terminal
tyrosine phosphorylation site, and lack a signal sequence.
Annexin II, a major cellular substrate of the tyrosine kinase encoded by
the SRC oncogene (190090), belongs to the annexin family of
Ca(2+)-dependent phospholipid- and membrane-binding proteins. By
screening a cDNA expression library generated from highly purified human
osteoclast-like multinuclear cells (MNC) formed in long-term bone marrow
cultures, Takahashi et al. (1994) identified a candidate clone that
stimulated MNC formation. Sequence analysis showed that this cDNA
encoded annexin II. Further studies yielded results suggesting that ANX2
is an autocrine factor that enhances osteoclast formation and bone
resorption, a previously unknown function for this molecule.
GENE FUNCTION
Formation of the apical surface and lumen is a fundamental step in
epithelial organ development. Martin-Belmonte et al. (2007) showed that
Pten (601728) localized to the apical plasma membrane during epithelial
morphogenesis to mediate enrichment of phosphatidylinositol
4,5-bisphosphate (PtdIns(4,5)P2) at this domain during cyst development
in a 3-dimensional Madin-Darby canine kidney cell system. Ectopic
PtdIns(4,5)P2 at the basolateral surface caused apical proteins to
relocalize to the basolateral surface. Anx2 bound PtdIns(4,5)P2 and was
recruited to the apical surface. Anx2 bound Cdc42 (116952) and recruited
it to the apical surface, and Cdc42 in turn recruited the Par6
(607484)/atypical protein kinase C (aPKC; see 176982) complex to the
apical surface. Loss of function of Pten, Anx2, Cdc42, or aPKC prevented
normal development of the apical surface and lumen. Martin-Belmonte et
al. (2007) concluded that PTEN, PtdIns(4,5)P2, ANX2, CDC42, and aPKC
control apical plasma membrane and lumen formation.
GENE STRUCTURE
Spano et al. (1990) isolated and characterized human genomic clones of
the gene encoding lipocortin II (LIP2) and of 3 pseudogenes. The LIP2
gene is at least 40 kb long and consists of 13 exons. The 3 LIP2
pseudogenes show typical features of retroposons.
MAPPING
Spano et al. (1990) reported experiments which, together with the data
published by Huebner et al. (1988), led them to conclude that the LIP2
gene is located on chromosome 15. Richard et al. (1994) presented an
integration of the physical, expression, and genetic maps of human
chromosome 15. They placed the ANXA2 gene in their region IV, i.e.,
15q21-q22, thus confirming the previous localization.
- Pseudogenes
By use of cDNAs in somatic cell hybrid analysis and in situ
hybridization, Huebner et al. (1987, 1988) mapped the LPC2A (LIP2P1)
locus to 4q21-q31. Spano et al. (1990) mapped the 3 LIP2 pseudogenes to
chromosomes 4 (ANX2P1), 9 (ANX2P2) and 10 (ANX2P3). The coexistence on
chromosome 9 of the LIP1 gene (151690) and a LIP pseudogene was
considered fortuitous.
By means of a lipocortin cDNA in somatic cell hybrid analysis and in
situ chromosome hybridization, Huebner et al. (1987, 1988) mapped LPC2B
(ANX2P2) to chromosome 9. Thus, LPC1 and LPC2B are syntenic. LPC2B is
located proximal to ABL (189980). Calpactin I is a synonym for
lipocortin II.
Huebner et al. (1987, 1988) mapped the LPC2C (ANX2P3) gene to 10q21-q22.
ANIMAL MODEL
Ling et al. (2004) generated Anxa2-null mice that displayed deposition
of fibrin in the microvasculature and incomplete clearance of
injury-induced arterial thrombi. The null mice demonstrated normal lysis
of fibrin-containing plasma clots, but tissue plasminogen activator
(tPA; 173370)-dependent plasmin generation at the endothelial cell
surface was markedly deficient. Directed migration of Anxa2-null
endothelial cells through fibrin and collagen lattices in vitro was also
reduced, and a peptide mimicking ANXA2 sequences necessary for tPA
binding blocked endothelial cell invasion of Matrigel implants in
wildtype mice. In addition, Anxa2-null mice displayed markedly
diminished neovascularization of fibroblast growth factor (see
131220)-stimulated cornea and of oxygen-primed neonatal retina.
Capillary sprouting from Anxa2-deficient aortic ring explants was
markedly reduced in association with severe impairment of activation of
metalloproteinase-9 (MMP9; 120361) and -13 (MMP13; 600108). Ling et al.
(2004) concluded that ANXA2 is a regulator of cell surface plasmin
generation and that impaired endothelial cell fibrinolytic activity
constitutes a barrier to effective neoangiogenesis.
*FIELD* RF
1. Huang, K.-S.; Wallner, B. P.; Mattaliano, R. J.; Tizard, R.; Burne,
C.; Frey, A.; Hession, C.; McGray, P.; Sinclair, L. K.; Chow, E. P.;
Browning, J. L.; Ramachandran, K. L.; Tang, J.; Smart, J. E.; Pepinsky,
R. B.: Two human 35 kd inhibitors of phospholipase A2 are related
to substrates of pp60(v-src) and of the epidermal growth factor receptor/kinase. Cell 46:
191-199, 1986.
2. 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.
3. 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.
4. Ling, Q.; Jacovina, A. T.; Deora, A.; Febbraio, M.; Simantov, R.;
Silverstein, R. L.; Hempstead, B.; Mark, W. H.; Hajjar, K. A.: Annexin
II regulates fibrin homeostasis and neoangiogenesis in vivo. J. Clin.
Invest. 113: 38-48, 2004.
5. Martin-Belmonte, F.; Gassama, A.; Datta, A.; Yu, W.; Rescher, U.;
Gerke, V.; Mostov, K.: PTEN-mediated apical segregation of phosphoinositides
controls epithelial morphogenesis through Cdc42. Cell 128: 383-397,
2007.
6. Richard, I.; Broux, O.; Chiannilkulchai, N.; Fougerousse, F.; Allamand,
V.; Bourg, N.; Brenguier, L.; Devaud, C.; Pasturaud, P.; Roudaut,
C.; Lorenzo, F.; Sebastiani-Kabatchis, C.; Schultz, R. A.; Polymeropoulos,
M. H.; Gyapay, G.; Auffray, C.; Beckmann, J. S.: Regional localization
of human chromosome 15 loci. Genomics 23: 619-627, 1994.
7. Spano, F.; Raugei, G.; Palla, E.; Colella, C.; Melli, M.: Characterization
of the human lipocortin-2-encoding multigene family: its structure
suggests the existence of a short amino acid unit undergoing duplication. Gene 95:
243-251, 1990.
8. Takahashi, S.; Reddy, S. V.; Chirgwin, J. M.; Devlin, R.; Haipek,
C.; Anderson, J.; Roodman, G. D.: Cloning and identification of annexin
II as an autocrine/paracrine factor that increases osteoclast formation
and bone resorption. J. Biol. Chem. 269: 28696-28701, 1994.
*FIELD* CN
Matthew B. Gross - updated: 5/11/2010
Marla J. F. O'Neill - updated: 3/30/2004
Patricia A. Hartz - updated: 3/22/2004
*FIELD* CD
Victor A. McKusick: 9/23/1987
*FIELD* ED
wwang: 05/17/2010
mgross: 5/11/2010
terry: 3/16/2005
tkritzer: 3/30/2004
mgross: 3/30/2004
terry: 3/22/2004
carol: 8/4/2003
alopez: 6/5/2002
mgross: 9/17/1999
alopez: 5/13/1999
terry: 7/31/1998
dkim: 7/24/1998
mark: 1/20/1997
mark: 1/18/1997
carol: 1/30/1995
carol: 11/12/1993
carol: 7/24/1992
supermim: 3/16/1992
carol: 6/6/1991
carol: 3/19/1991