ANXA2_HUMAN
ID ANXA2_HUMAN Reviewed; 339 AA.
AC P07355; Q567R4; Q6N0B3; Q8TBV2; Q96DD5; Q9UDH8;
DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 250.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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., Frey A.,
RA Hession C., McGray P., Sinclair L.K., Chow E.P., Browning J.L.,
RA Ramachandran K.L., Tang J., Smart J.E., Pepinsky R.B.;
RT "Two human 35 kd inhibitors of phospholipase A2 are related to substrates
RT of pp60v-src and of the epidermal growth factor 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: its
RT structure suggests the existence of a short amino acid unit undergoing
RT 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 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., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA 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., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT LEU-98.
RC TISSUE=Brain, Colon, Pancreas, Prostate, Skin, Testis, and 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 project:
RT 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 213-220,
RP CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT SER-2, AND IDENTIFICATION
RP BY 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; DOI=10.1016/s0021-9258(19)67770-7;
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), is
RT part of the primer recognition protein complex that interacts with DNA
RT 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 INTERACTION
RP WITH HCMV (MICROBIAL INFECTION).
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; DOI=10.1128/mcb.6.7.2738-2744.1986;
RA Gould K.L., Woodgett J.R., Isacke C.M., Hunter T.;
RT "The protein-tyrosine kinase substrate p36 is also a substrate for protein
RT kinase C in vitro and in vivo.";
RL Mol. Cell. Biol. 6:2738-2744(1986).
RN [13]
RP INTERACTION WITH CEACAM1.
RX PubMed=14522961; DOI=10.1074/jbc.m309115200;
RA Kirshner J., Schumann D., Shively J.E.;
RT "CEACAM1, a cell-cell adhesion molecule, directly associates with annexin
RT II in a three-dimensional model of mammary morphogenesis.";
RL J. Biol. Chem. 278:50338-50345(2003).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Lymphoblast;
RX PubMed=14654843; DOI=10.1038/nature02166;
RA Andersen J.S., Wilkinson C.J., Mayor T., Mortensen P., Nigg E.A., Mann M.;
RT "Proteomic characterization of the human centrosome by protein correlation
RT profiling.";
RL Nature 426:570-574(2003).
RN [15]
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 translocation
RT of annexin 2 to the cell surface.";
RL J. Biol. Chem. 279:43411-43418(2004).
RN [16]
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 [17]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J.,
RA Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S.,
RA Shabanowitz J., Hearing V.J., Wu C., Appella E., 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 [18]
RP FUNCTION, INTERACTION WITH PCSK9, AND MUTAGENESIS OF 77-ARG--LYS-81;
RP 80-LYS--ALA-84 AND LYS-88.
RX PubMed=18799458; DOI=10.1074/jbc.m805971200;
RA Mayer G., Poirier S., Seidah N.G.;
RT "Annexin A2 is a C-terminal PCSK9-binding protein that regulates endogenous
RT low density lipoprotein receptor levels.";
RL J. Biol. Chem. 283:31791-31801(2008).
RN [19]
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., Buerckstuemmer T.,
RA 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 [20]
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 in
RT trabecular meshwork cell elongation and motility.";
RL PLoS ONE 6:E23070-E23070(2011).
RN [21]
RP FUNCTION, VARIANT LEU-98, CHARACTERIZATION OF VARIANT LEU-98, AND
RP MUTAGENESIS OF 28-LYS--GLU-36; 37-ARG--LYS-47; 77-ARG--LYS-80 AND
RP 77-ARG--LYS-81.
RX PubMed=22848640; DOI=10.1371/journal.pone.0041865;
RA Seidah N.G., Poirier S., Denis M., Parker R., Miao B., Mapelli C., Prat A.,
RA Wassef H., Davignon J., Hajjar K.A., Mayer G.;
RT "Annexin A2 is a natural extrahepatic inhibitor of the PCSK9-induced LDL
RT receptor degradation.";
RL PLoS ONE 7:E41865-E41865(2012).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-184, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [23]
RP FUNCTION, INTERACTION WITH PCSK9, AND RNA-BINDING.
RX PubMed=24808179; DOI=10.1074/jbc.m113.541094;
RA Ly K., Saavedra Y.G., Canuel M., Routhier S., Desjardins R., Hamelin J.,
RA Mayne J., Lazure C., Seidah N.G., Day R.;
RT "Annexin A2 reduces PCSK9 protein levels via a translational mechanism and
RT interacts with the M1 and M2 domains of PCSK9.";
RL J. Biol. Chem. 289:17732-17746(2014).
RN [24]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [25]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-49, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25114211; DOI=10.1073/pnas.1413825111;
RA Impens F., Radoshevich L., Cossart P., Ribet D.;
RT "Mapping of SUMO sites and analysis of SUMOylation changes induced by
RT external stimuli.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:12432-12437(2014).
RN [26]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [27]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-49, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [28]
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).
RN [29] {ECO:0007744|PDB:5LPU, ECO:0007744|PDB:5LPX, ECO:0007744|PDB:5LQ0, ECO:0007744|PDB:5LQ2}
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 2-339, INTERACTION WITH S100A4,
RP PHOSPHORYLATION AT TYR-24 AND SER-26, AND MUTAGENESIS OF SER-26.
RX PubMed=28669632; DOI=10.1016/j.str.2017.06.001;
RA Ecsedi P., Kiss B., Gogl G., Radnai L., Buday L., Koprivanacz K.,
RA Liliom K., Leveles I., Vertessy B., Jeszenoi N., Hetenyi C., Schlosser G.,
RA Katona G., Nyitray L.;
RT "Regulation of the Equilibrium between Closed and Open Conformations of
RT Annexin A2 by N-Terminal Phosphorylation and S100A4-Binding.";
RL Structure 25:1195-1207.e5(2017).
CC -!- FUNCTION: Calcium-regulated membrane-binding protein whose affinity for
CC calcium is greatly enhanced by anionic phospholipids. It binds two
CC calcium ions with high affinity. May be involved in heat-stress
CC response. Inhibits PCSK9-enhanced LDLR degradation, probably reduces
CC PCSK9 protein levels via a translational mechanism but also competes
CC with LDLR for binding with PCSK9 (PubMed:18799458, PubMed:24808179,
CC PubMed:22848640). {ECO:0000269|PubMed:18799458,
CC ECO:0000269|PubMed:22848640, ECO:0000269|PubMed:24808179}.
CC -!- SUBUNIT: Heterotetramer containing 2 light chains of S100A10/p11 and 2
CC heavy chains of ANXA2/p36 (By similarity). Interacts with ATP1B1 (By
CC similarity). Interacts with DYSF (By similarity). Interacts with COCH
CC (PubMed:21886777). Interacts (via repeat Annexin 1) with PCSK9 (via the
CC C-terminal domain); the interaction inhibits the degradation of LDLR
CC (PubMed:18799458). Interacts with CEACAM1 (via the cytoplasmic domain);
CC this interaction is regulated by phosphorylation of CEACAM1
CC (PubMed:14522961). Interacts with APPL2 and APPL1; targets APPL2 to
CC endosomes and acting in parallel to RAB5A (By similarity). Interacts
CC with S100A4 (PubMed:28669632). {ECO:0000250|UniProtKB:A2SW69,
CC ECO:0000250|UniProtKB:P07356, ECO:0000250|UniProtKB:Q6TEQ7,
CC ECO:0000269|PubMed:14522961, ECO:0000269|PubMed:18799458,
CC ECO:0000269|PubMed:21886777}.
CC -!- SUBUNIT: (Microbial infection) Interacts with human cytomegalovirus
CC (HCMV). {ECO:0000269|PubMed:8117306}.
CC -!- INTERACTION:
CC P07355; P07355: ANXA2; NbExp=5; IntAct=EBI-352622, EBI-352622;
CC P07355; Q15811-1: ITSN1; NbExp=2; IntAct=EBI-352622, EBI-8052560;
CC P07355; P10636-8: MAPT; NbExp=7; IntAct=EBI-352622, EBI-366233;
CC P07355; P40692: MLH1; NbExp=7; IntAct=EBI-352622, EBI-744248;
CC P07355; P12004: PCNA; NbExp=2; IntAct=EBI-352622, EBI-358311;
CC P07355; Q8NBP7: PCSK9; NbExp=7; IntAct=EBI-352622, EBI-7539251;
CC P07355; Q9NUX5: POT1; NbExp=2; IntAct=EBI-352622, EBI-752420;
CC P07355; P60903: S100A10; NbExp=4; IntAct=EBI-352622, EBI-717048;
CC P07355; Q15599: SLC9A3R2; NbExp=6; IntAct=EBI-352622, EBI-1149760;
CC P07355; Q14508: WFDC2; NbExp=36; IntAct=EBI-352622, EBI-723529;
CC P07355; P75409: MPN_372; Xeno; NbExp=6; IntAct=EBI-352622, EBI-2259548;
CC P07355; P15363: p37; Xeno; NbExp=24; IntAct=EBI-352622, EBI-12740262;
CC P07355; B7UM99: tir; Xeno; NbExp=3; IntAct=EBI-352622, EBI-2504426;
CC P07355; Q7DB77: tir; Xeno; NbExp=2; IntAct=EBI-352622, EBI-6480811;
CC P07355; PRO_0000045602 [Q99IB8]; Xeno; NbExp=5; IntAct=EBI-352622, EBI-6927873;
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix, basement membrane {ECO:0000269|PubMed:17081065}. Melanosome
CC {ECO:0000269|PubMed:17081065}. Note=In the lamina beneath the plasma
CC membrane. Identified by mass spectrometry in melanosome fractions from
CC stage I to stage IV. Translocated from the cytoplasm to the cell
CC surface through a Golgi-independent 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 calcium
CC and phospholipid.
CC -!- PTM: Phosphorylation of Tyr-24 enhances heat stress-induced
CC translocation to the cell surface. {ECO:0000269|PubMed:15302870,
CC ECO:0000269|PubMed:2946940}.
CC -!- PTM: ISGylated. {ECO:0000269|PubMed:16139798}.
CC -!- MISCELLANEOUS: It may cross-link plasma membrane phospholipids with
CC actin and the cytoskeleton and be involved with exocytosis.
CC -!- SIMILARITY: Belongs to the annexin family. {ECO:0000255|PROSITE-
CC ProRule:PRU01245, ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH66955.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Red velvet - Issue 86 of
CC September 2007;
CC URL="https://web.expasy.org/spotlight/back_issues/086";
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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 CCDS; CCDS10175.1; -. [P07355-1]
DR CCDS; CCDS32256.1; -. [P07355-2]
DR PIR; A23942; LUHU36.
DR RefSeq; NP_001002857.1; NM_001002857.1. [P07355-1]
DR RefSeq; NP_001002858.1; NM_001002858.2. [P07355-2]
DR RefSeq; NP_001129487.1; NM_001136015.2. [P07355-1]
DR RefSeq; NP_004030.1; NM_004039.2. [P07355-1]
DR RefSeq; XP_016877579.1; XM_017022090.1. [P07355-1]
DR RefSeq; XP_016877580.1; XM_017022091.1. [P07355-1]
DR PDB; 1W7B; X-ray; 1.52 A; A=1-339.
DR PDB; 1XJL; X-ray; 2.59 A; A/B=21-339.
DR PDB; 2HYU; X-ray; 1.86 A; A=32-339.
DR PDB; 2HYV; X-ray; 1.42 A; A=32-339.
DR PDB; 2HYW; X-ray; 2.10 A; A/B=32-339.
DR PDB; 4DRW; X-ray; 3.50 A; A/B/C/D=2-16.
DR PDB; 4FTG; X-ray; 2.51 A; C/D=2-16.
DR PDB; 4HRH; X-ray; 3.00 A; A/B=2-16.
DR PDB; 5LPU; X-ray; 2.10 A; A/B=2-339.
DR PDB; 5LPX; X-ray; 1.90 A; A=2-339.
DR PDB; 5LQ0; X-ray; 2.90 A; A/B=2-339.
DR PDB; 5LQ2; X-ray; 3.40 A; A/B=2-339.
DR PDB; 5N7D; X-ray; 2.30 A; A/B=22-339.
DR PDB; 5N7F; X-ray; 2.30 A; A/B=22-339.
DR PDB; 5N7G; X-ray; 2.95 A; A/B=22-339.
DR PDB; 6TWQ; X-ray; 2.65 A; A/B=22-339.
DR PDB; 6TWU; X-ray; 2.40 A; A/B=22-339.
DR PDB; 6TWX; X-ray; 2.30 A; A/B=22-339.
DR PDB; 6TWY; X-ray; 2.30 A; A/B=22-339.
DR PDB; 7DTO; X-ray; 2.80 A; A=31-339.
DR PDB; 7NMI; X-ray; 2.10 A; B=29-339.
DR PDBsum; 1W7B; -.
DR PDBsum; 1XJL; -.
DR PDBsum; 2HYU; -.
DR PDBsum; 2HYV; -.
DR PDBsum; 2HYW; -.
DR PDBsum; 4DRW; -.
DR PDBsum; 4FTG; -.
DR PDBsum; 4HRH; -.
DR PDBsum; 5LPU; -.
DR PDBsum; 5LPX; -.
DR PDBsum; 5LQ0; -.
DR PDBsum; 5LQ2; -.
DR PDBsum; 5N7D; -.
DR PDBsum; 5N7F; -.
DR PDBsum; 5N7G; -.
DR PDBsum; 6TWQ; -.
DR PDBsum; 6TWU; -.
DR PDBsum; 6TWX; -.
DR PDBsum; 6TWY; -.
DR PDBsum; 7DTO; -.
DR PDBsum; 7NMI; -.
DR AlphaFoldDB; P07355; -.
DR SMR; P07355; -.
DR BioGRID; 106799; 308.
DR ComplexPortal; CPX-130; ANXA2-PCSK9 complex.
DR ComplexPortal; CPX-850; AHNAK - Annexin A2 - S100-A10 complex.
DR ComplexPortal; CPX-853; Annexin A2 - S100-A10 complex.
DR ComplexPortal; CPX-856; SMARCA3 - Annexin A2 - S100-A10 complex.
DR CORUM; P07355; -.
DR IntAct; P07355; 122.
DR MINT; P07355; -.
DR STRING; 9606.ENSP00000346032; -.
DR ChEMBL; CHEMBL1764938; -.
DR DrugBank; DB11638; Artenimol.
DR DrugBank; DB00591; Fluocinolone acetonide.
DR DrugBank; DB06245; Lanoteplase.
DR DrugBank; DB00031; Tenecteplase.
DR TCDB; 1.A.31.1.4; the annexin (annexin) family.
DR GlyGen; P07355; 1 site, 2 O-linked glycans (1 site).
DR iPTMnet; P07355; -.
DR MetOSite; P07355; -.
DR PhosphoSitePlus; P07355; -.
DR SwissPalm; P07355; -.
DR BioMuta; ANXA2; -.
DR DMDM; 113950; -.
DR DOSAC-COBS-2DPAGE; P07355; -.
DR REPRODUCTION-2DPAGE; IPI00455315; -.
DR REPRODUCTION-2DPAGE; P07355; -.
DR UCD-2DPAGE; P07355; -.
DR CPTAC; CPTAC-462; -.
DR EPD; P07355; -.
DR jPOST; P07355; -.
DR MassIVE; P07355; -.
DR MaxQB; P07355; -.
DR PaxDb; P07355; -.
DR PeptideAtlas; P07355; -.
DR PRIDE; P07355; -.
DR ProteomicsDB; 51995; -. [P07355-1]
DR ProteomicsDB; 51996; -. [P07355-2]
DR TopDownProteomics; P07355-1; -. [P07355-1]
DR Antibodypedia; 3808; 872 antibodies from 46 providers.
DR DNASU; 302; -.
DR Ensembl; ENST00000332680.8; ENSP00000346032.3; ENSG00000182718.18. [P07355-2]
DR Ensembl; ENST00000396024.7; ENSP00000379342.3; ENSG00000182718.18. [P07355-1]
DR Ensembl; ENST00000421017.6; ENSP00000411352.2; ENSG00000182718.18. [P07355-1]
DR Ensembl; ENST00000451270.7; ENSP00000387545.3; ENSG00000182718.18. [P07355-1]
DR Ensembl; ENST00000557906.6; ENSP00000452895.2; ENSG00000182718.18. [P07355-1]
DR Ensembl; ENST00000558558.6; ENSP00000452981.2; ENSG00000182718.18. [P07355-1]
DR Ensembl; ENST00000559818.6; ENSP00000453859.2; ENSG00000182718.18. [P07355-1]
DR Ensembl; ENST00000559956.6; ENSP00000453694.2; ENSG00000182718.18. [P07355-1]
DR Ensembl; ENST00000560468.6; ENSP00000452858.2; ENSG00000182718.18. [P07355-1]
DR Ensembl; ENST00000677968.1; ENSP00000503447.1; ENSG00000182718.18. [P07355-1]
DR Ensembl; ENST00000678061.1; ENSP00000503855.1; ENSG00000182718.18. [P07355-1]
DR Ensembl; ENST00000678450.1; ENSP00000504164.1; ENSG00000182718.18. [P07355-1]
DR Ensembl; ENST00000678870.1; ENSP00000503757.1; ENSG00000182718.18. [P07355-1]
DR Ensembl; ENST00000679109.1; ENSP00000504035.1; ENSG00000182718.18. [P07355-1]
DR GeneID; 302; -.
DR KEGG; hsa:302; -.
DR MANE-Select; ENST00000451270.7; ENSP00000387545.3; NM_004039.3; NP_004030.1.
DR UCSC; uc002agk.4; human. [P07355-1]
DR CTD; 302; -.
DR DisGeNET; 302; -.
DR GeneCards; ANXA2; -.
DR HGNC; HGNC:537; ANXA2.
DR HPA; ENSG00000182718; Tissue enhanced (esophagus).
DR MIM; 151740; gene.
DR neXtProt; NX_P07355; -.
DR OpenTargets; ENSG00000182718; -.
DR PharmGKB; PA24827; -.
DR VEuPathDB; HostDB:ENSG00000182718; -.
DR eggNOG; KOG0819; Eukaryota.
DR GeneTree; ENSGT00940000154257; -.
DR HOGENOM; CLU_025300_0_0_1; -.
DR InParanoid; P07355; -.
DR OMA; EVDLMRI; -.
DR OrthoDB; 856254at2759; -.
DR TreeFam; TF105452; -.
DR PathwayCommons; P07355; -.
DR Reactome; R-HSA-445355; Smooth Muscle Contraction.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-75205; Dissolution of Fibrin Clot.
DR Reactome; R-HSA-8950505; Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation.
DR SignaLink; P07355; -.
DR SIGNOR; P07355; -.
DR BioGRID-ORCS; 302; 13 hits in 1081 CRISPR screens.
DR ChiTaRS; ANXA2; human.
DR EvolutionaryTrace; P07355; -.
DR GeneWiki; Annexin_A2; -.
DR GenomeRNAi; 302; -.
DR Pharos; P07355; Tbio.
DR PRO; PR:P07355; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; P07355; protein.
DR Bgee; ENSG00000182718; Expressed in bronchial epithelial cell and 203 other tissues.
DR ExpressionAtlas; P07355; baseline and differential.
DR Genevisible; P07355; HS.
DR GO; GO:0005912; C:adherens junction; HDA:BHF-UCL.
DR GO; GO:1990665; C:AnxA2-p11 complex; IDA:UniProtKB.
DR GO; GO:0035578; C:azurophil granule lumen; TAS:Reactome.
DR GO; GO:0005604; C:basement membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016323; C:basolateral plasma membrane; ISS:BHF-UCL.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0001533; C:cornified envelope; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005769; C:early endosome; IEA:Ensembl.
DR GO; GO:0005768; C:endosome; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; HDA:BHF-UCL.
DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR GO; GO:0019897; C:extrinsic component of plasma membrane; IEA:Ensembl.
DR GO; GO:0031902; C:late endosome membrane; IDA:UniProtKB.
DR GO; GO:0005811; C:lipid droplet; IDA:UniProtKB.
DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0030496; C:midbody; IDA:UniProtKB.
DR GO; GO:0035749; C:myelin sheath adaxonal region; IEA:Ensembl.
DR GO; GO:0016363; C:nuclear matrix; IC:ComplexPortal.
DR GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR GO; GO:1990667; C:PCSK9-AnxA2 complex; IDA:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL.
DR GO; GO:0098797; C:plasma membrane protein complex; IPI:ComplexPortal.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IC:ComplexPortal.
DR GO; GO:0042383; C:sarcolemma; IEA:Ensembl.
DR GO; GO:0043220; C:Schmidt-Lanterman incisure; IEA:Ensembl.
DR GO; GO:0031982; C:vesicle; HDA:UniProtKB.
DR GO; GO:0098641; F:cadherin binding involved in cell-cell adhesion; HDA:BHF-UCL.
DR GO; GO:0005262; F:calcium channel activity; IBA:GO_Central.
DR GO; GO:0005509; F:calcium ion binding; IBA:GO_Central.
DR GO; GO:0005544; F:calcium-dependent phospholipid binding; IDA:UniProtKB.
DR GO; GO:0048306; F:calcium-dependent protein binding; IPI:GO_Central.
DR GO; GO:0008092; F:cytoskeletal protein binding; IEA:InterPro.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IMP:UniProtKB.
DR GO; GO:0001786; F:phosphatidylserine binding; IBA:GO_Central.
DR GO; GO:0019834; F:phospholipase A2 inhibitor activity; IDA:UniProtKB.
DR GO; GO:0002020; F:protease binding; IPI:BHF-UCL.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0044548; F:S100 protein binding; IPI:UniProtKB.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IDA:BHF-UCL.
DR GO; GO:0046790; F:virion binding; IBA:GO_Central.
DR GO; GO:0001525; P:angiogenesis; IEP:UniProtKB.
DR GO; GO:0030199; P:collagen fibril organization; IEA:Ensembl.
DR GO; GO:0042730; P:fibrinolysis; IEA:Ensembl.
DR GO; GO:0001765; P:membrane raft assembly; IMP:UniProtKB.
DR GO; GO:0042789; P:mRNA transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0032804; P:negative regulation of low-density lipoprotein particle receptor catabolic process; IDA:BHF-UCL.
DR GO; GO:0002091; P:negative regulation of receptor internalization; IDA:ComplexPortal.
DR GO; GO:0036035; P:osteoclast development; IDA:UniProtKB.
DR GO; GO:0045921; P:positive regulation of exocytosis; IC:ComplexPortal.
DR GO; GO:1905581; P:positive regulation of low-density lipoprotein particle clearance; IDA:BHF-UCL.
DR GO; GO:1905597; P:positive regulation of low-density lipoprotein particle receptor binding; IDA:BHF-UCL.
DR GO; GO:1905599; P:positive regulation of low-density lipoprotein receptor activity; IMP:BHF-UCL.
DR GO; GO:1905686; P:positive regulation of plasma membrane repair; IC:ComplexPortal.
DR GO; GO:0010756; P:positive regulation of plasminogen activation; IDA:ComplexPortal.
DR GO; GO:0001921; P:positive regulation of receptor recycling; IDA:BHF-UCL.
DR GO; GO:1905602; P:positive regulation of receptor-mediated endocytosis involved in cholesterol transport; IDA:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0044090; P:positive regulation of vacuole organization; IMP:AgBase.
DR GO; GO:0031340; P:positive regulation of vesicle fusion; IDA:UniProtKB.
DR GO; GO:0050767; P:regulation of neurogenesis; IEA:Ensembl.
DR GO; GO:0006900; P:vesicle budding from membrane; IMP:UniProtKB.
DR DisProt; DP02735; -.
DR Gene3D; 1.10.220.10; -; 4.
DR InterPro; IPR001464; Annexin.
DR InterPro; IPR018502; Annexin_repeat.
DR InterPro; IPR018252; Annexin_repeat_CS.
DR InterPro; IPR037104; Annexin_sf.
DR InterPro; IPR002389; ANX2.
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 SUPFAM; SSF47874; SSF47874; 1.
DR PROSITE; PS00223; ANNEXIN_1; 4.
DR PROSITE; PS51897; ANNEXIN_2; 4.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Annexin;
KW Basement membrane; Calcium; Calcium/phospholipid-binding;
KW Direct protein sequencing; Extracellular matrix; Host-virus interaction;
KW Isopeptide bond; Phosphoprotein; Reference proteome; Repeat; RNA-binding;
KW Secreted; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.7"
FT CHAIN 2..339
FT /note="Annexin A2"
FT /id="PRO_0000067470"
FT REPEAT 33..104
FT /note="Annexin 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01245"
FT REPEAT 105..176
FT /note="Annexin 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01245"
FT REPEAT 189..261
FT /note="Annexin 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01245"
FT REPEAT 265..336
FT /note="Annexin 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01245"
FT REGION 2..24
FT /note="S100A10-binding site"
FT /evidence="ECO:0000255"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000269|Ref.7"
FT MOD_RES 24
FT /note="Phosphotyrosine; by SRC"
FT /evidence="ECO:0000269|PubMed:15302870,
FT ECO:0000269|PubMed:28669632"
FT MOD_RES 26
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000269|PubMed:28669632,
FT ECO:0000269|PubMed:2946940"
FT MOD_RES 49
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P07356"
FT MOD_RES 152
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P07356"
FT MOD_RES 184
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 199
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P07356"
FT MOD_RES 227
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P07356"
FT CROSSLNK 49
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1); alternate"
FT /evidence="ECO:0007744|PubMed:25114211"
FT CROSSLNK 49
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 1
FT /note="M -> MGRQLAGCGDAGKKASFKM (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_038091"
FT VARIANT 98
FT /note="V -> L (does not affect interaction with PCSK9;
FT dbSNP:rs17845226)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:22848640"
FT /id="VAR_012982"
FT MUTAGEN 24
FT /note="Y->A: Abolishes heat stress-induced cell surface
FT localization."
FT /evidence="ECO:0000269|PubMed:15302870"
FT MUTAGEN 26
FT /note="S->E: Stronger interaction with S100A4."
FT /evidence="ECO:0000269|PubMed:28669632"
FT MUTAGEN 28..36
FT /note="KAYTNFDAE->SAYTNFNAS: No effect on interaction with
FT PCSK9."
FT /evidence="ECO:0000269|PubMed:22848640"
FT MUTAGEN 37..47
FT /note="RDALNIETAIK->SDALNIHTAIM: Slightly decreases
FT interaction with PCSK9."
FT /evidence="ECO:0000269|PubMed:22848640"
FT MUTAGEN 77..81
FT /note="RRTKK->AATAA: Strongly decreases interaction with
FT PCSK9."
FT /evidence="ECO:0000269|PubMed:18799458,
FT ECO:0000269|PubMed:22848640"
FT MUTAGEN 77..80
FT /note="RRTK->AATA: Decreases interaction with PCSK9.
FT Strongly decreases interaction with PCSK9; when associated
FT with K-88."
FT /evidence="ECO:0000269|PubMed:18799458"
FT MUTAGEN 80..84
FT /note="KKELA->GKPLD: No effect on interaction with PCSK9."
FT /evidence="ECO:0000269|PubMed:18799458"
FT MUTAGEN 88
FT /note="K->A: Strongly decreases interaction with PCSK9;
FT when associated with 77-A--A-80."
FT /evidence="ECO:0000269|PubMed:18799458"
FT CONFLICT 29
FT /note="A -> P (in Ref. 9; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 166
FT /note="D -> G (in Ref. 4; CAE45704)"
FT /evidence="ECO:0000305"
FT CONFLICT 293
FT /note="V -> A (in Ref. 6; AAH23990)"
FT /evidence="ECO:0000305"
FT HELIX 4..12
FT /evidence="ECO:0007829|PDB:5LPU"
FT TURN 22..24
FT /evidence="ECO:0007829|PDB:6TWX"
FT HELIX 35..47
FT /evidence="ECO:0007829|PDB:2HYV"
FT STRAND 48..50
FT /evidence="ECO:0007829|PDB:5N7D"
FT HELIX 53..60
FT /evidence="ECO:0007829|PDB:2HYV"
FT HELIX 65..79
FT /evidence="ECO:0007829|PDB:2HYV"
FT HELIX 83..90
FT /evidence="ECO:0007829|PDB:2HYV"
FT HELIX 93..103
FT /evidence="ECO:0007829|PDB:2HYV"
FT HELIX 106..117
FT /evidence="ECO:0007829|PDB:2HYV"
FT STRAND 120..122
FT /evidence="ECO:0007829|PDB:1W7B"
FT HELIX 125..134
FT /evidence="ECO:0007829|PDB:2HYV"
FT HELIX 137..151
FT /evidence="ECO:0007829|PDB:2HYV"
FT HELIX 155..161
FT /evidence="ECO:0007829|PDB:2HYV"
FT HELIX 165..175
FT /evidence="ECO:0007829|PDB:2HYV"
FT HELIX 188..200
FT /evidence="ECO:0007829|PDB:2HYV"
FT TURN 201..204
FT /evidence="ECO:0007829|PDB:2HYV"
FT STRAND 205..207
FT /evidence="ECO:0007829|PDB:2HYV"
FT HELIX 210..219
FT /evidence="ECO:0007829|PDB:2HYV"
FT HELIX 222..232
FT /evidence="ECO:0007829|PDB:2HYV"
FT TURN 233..235
FT /evidence="ECO:0007829|PDB:2HYV"
FT STRAND 236..238
FT /evidence="ECO:0007829|PDB:7DTO"
FT HELIX 240..247
FT /evidence="ECO:0007829|PDB:2HYV"
FT HELIX 250..264
FT /evidence="ECO:0007829|PDB:2HYV"
FT HELIX 266..278
FT /evidence="ECO:0007829|PDB:2HYV"
FT STRAND 279..282
FT /evidence="ECO:0007829|PDB:2HYV"
FT HELIX 285..295
FT /evidence="ECO:0007829|PDB:2HYV"
FT TURN 296..298
FT /evidence="ECO:0007829|PDB:2HYV"
FT HELIX 300..311
FT /evidence="ECO:0007829|PDB:2HYV"
FT HELIX 315..322
FT /evidence="ECO:0007829|PDB:2HYV"
FT HELIX 325..335
FT /evidence="ECO:0007829|PDB:2HYV"
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
