Full text data of ANXA5
ANXA5
(ANX5, ENX2, PP4)
[Confidence: low (only semi-automatic identification from reviews)]
Annexin A5 (Anchorin CII; Annexin V; Annexin-5; Calphobindin I; CBP-I; Endonexin II; Lipocortin V; Placental anticoagulant protein 4; PP4; Placental anticoagulant protein I; PAP-I; Thromboplastin inhibitor; Vascular anticoagulant-alpha; VAC-alpha)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Annexin A5 (Anchorin CII; Annexin V; Annexin-5; Calphobindin I; CBP-I; Endonexin II; Lipocortin V; Placental anticoagulant protein 4; PP4; Placental anticoagulant protein I; PAP-I; Thromboplastin inhibitor; Vascular anticoagulant-alpha; VAC-alpha)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P08758
ID ANXA5_HUMAN Reviewed; 320 AA.
AC P08758; D3DNW7; Q6FHB3; Q6FI16; Q8WV69; Q9UDH9;
DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 166.
DE RecName: Full=Annexin A5;
DE AltName: Full=Anchorin CII;
DE AltName: Full=Annexin V;
DE AltName: Full=Annexin-5;
DE AltName: Full=Calphobindin I;
DE Short=CBP-I;
DE AltName: Full=Endonexin II;
DE AltName: Full=Lipocortin V;
DE AltName: Full=Placental anticoagulant protein 4;
DE Short=PP4;
DE AltName: Full=Placental anticoagulant protein I;
DE Short=PAP-I;
DE AltName: Full=Thromboplastin inhibitor;
DE AltName: Full=Vascular anticoagulant-alpha;
DE Short=VAC-alpha;
GN Name=ANXA5; Synonyms=ANX5, ENX2, PP4;
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=2964863; DOI=10.1021/bi00399a011;
RA Funakoshi T., Hendrickson L.E., McMullen B.A., Fujikawa K.;
RT "Primary structure of human placental anticoagulant protein.";
RL Biochemistry 26:8087-8092(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 2-320.
RX PubMed=2963810;
RA Iwasaki A., Suda M., Nakao H., Nagoya T., Saino Y., Arai K.,
RA Mizoguchi T., Sato F., Yoshizaki H., Hirata M., Miyata T., Shidara Y.,
RA Murata M., Maki M.;
RT "Structure and expression of cDNA for an inhibitor of blood
RT coagulation isolated from human placenta: a new lipocortin-like
RT protein.";
RL J. Biochem. 102:1261-1273(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=2455636; DOI=10.1111/j.1432-1033.1988.tb14139.x;
RA Maurer-Fogy I., Reutelingsperger C.P.M., Pieters J., Bodo G.,
RA Stratowa C., Hauptmann R.;
RT "Cloning and expression of cDNA for human vascular anticoagulant, a
RT Ca2+-dependent phospholipid-binding protein.";
RL Eur. J. Biochem. 174:585-592(1988).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2967291;
RA Kaplan R., Jaye M., Burgess W.H., Schlaepfer D.D., Haigler H.T.;
RT "Cloning and expression of cDNA for human endonexin II, a Ca2+ and
RT phospholipid binding protein.";
RL J. Biol. Chem. 263:8037-8043(1988).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2968983;
RA Pepinsky R.B., Tizard R., Mattaliano R.J., Sinclair L.K., Miller G.T.,
RA Browning J.L., Chow E.P., Burne C., Huang K.-S., Pratt D., Wachter L.,
RA Hession C., Frey A.Z., Wallner B.P.;
RT "Five distinct calcium and phospholipid binding proteins share
RT homology with lipocortin I.";
RL J. Biol. Chem. 263:10799-10811(1988).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2967495; DOI=10.1073/pnas.85.11.3708;
RA Grundmann U., Abel K.-J., Bohn H., Loebermann H., Lottspeich F.,
RA Kuepper H.;
RT "Characterization of cDNA encoding human placental anticoagulant
RT protein (PP4): homology with the lipocortin family.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:3708-3712(1988).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Lung;
RX PubMed=7958998; DOI=10.1016/0378-1119(94)90157-0;
RA Fernandez M.-P., Morgan R.O., Fernandez M.R., Carcedo M.-T.;
RT "The gene encoding human annexin V has a TATA-less promoter with a
RT high G+C content.";
RL Gene 149:253-260(1994).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8034319; DOI=10.1006/geno.1994.1201;
RA Cookson B.T., Engelhardt S., Smith C., Bamford H.A., Prochazka M.,
RA Tait J.F.;
RT "Organization of the human annexin V (ANX5) gene.";
RL Genomics 20:463-467(1994).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Neuroblastoma;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S.,
RA Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W.,
RA Korn B., Zuo D., Hu Y., LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [13]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Muscle, Ovary, and Skin;
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 [14]
RP PARTIAL PROTEIN SEQUENCE.
RX PubMed=2532007;
RA Rothhut R., Comera C., Cortial S., Haumont P.-Y., Diep Le K.H.,
RA Cavadore J.-C., Conard J., Russo-Marie F., Lederer F.;
RT "A 32 kDa lipocortin from human mononuclear cells appears to be
RT identical with the placental inhibitor of blood coagulation.";
RL Biochem. J. 263:929-935(1989).
RN [15]
RP PROTEIN SEQUENCE OF 7-18; 30-45; 187-201 AND 277-286, AND MASS
RP SPECTROMETRY.
RC TISSUE=Melanoma;
RA Quadroni M., Potts A., Barblan J., Bienvenut W.V.;
RL Submitted (JAN-2005) to UniProtKB.
RN [16]
RP PROTEIN SEQUENCE OF 21-31; 93-108; 176-188 AND 304-319, AND
RP INTERACTION WITH HBV.
RX PubMed=8249278; DOI=10.1006/viro.1993.1628;
RA Hertogs K., Leenders W.P., Depla E., De Bruin W.C., Meheus L.,
RA Raymackers J., Moshage H., Yap S.H.;
RT "Endonexin II, present on human liver plasma membranes, is a specific
RT binding protein of small hepatitis B virus (HBV) envelope protein.";
RL Virology 197:549-557(1993).
RN [17]
RP PROTEIN SEQUENCE OF 86-131; 259-297 AND 300-320.
RX PubMed=2957692; DOI=10.1073/pnas.84.17.6078;
RA Schlaepfer D.D., Mehlman T., Burgess W.H., Haigler H.T.;
RT "Structural and functional characterization of endonexin II, a
RT calcium- and phospholipid-binding protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:6078-6082(1987).
RN [18]
RP PROTEIN SEQUENCE OF 85-93.
RC TISSUE=Placenta;
RX PubMed=2974032;
RA Ahn N.G., Teller D.C., Bienkowski M.J., McMullen B.A., Lipkin E.W.,
RA de Haen C.;
RT "Sedimentation equilibrium analysis of five lipocortin-related
RT phospholipase A2 inhibitors from human placenta. Evidence against a
RT mechanistically relevant association between enzyme and inhibitor.";
RL J. Biol. Chem. 263:18657-18663(1988).
RN [19]
RP PROTEIN SEQUENCE OF 152-161 AND 246-260.
RC TISSUE=Adipocyte;
RX PubMed=15242332; DOI=10.1042/BJ20040647;
RA Aboulaich N., Vainonen J.P., Stralfors P., Vener A.V.;
RT "Vectorial proteomics reveal targeting, phosphorylation and specific
RT fragmentation of polymerase I and transcript release factor (PTRF) at
RT the surface of caveolae in human adipocytes.";
RL Biochem. J. 383:237-248(2004).
RN [20]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-101, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=16916647; DOI=10.1016/j.molcel.2006.06.026;
RA Kim S.C., Sprung R., Chen Y., Xu Y., Ball H., Pei J., Cheng T.,
RA Kho Y., Xiao H., Xiao L., Grishin N.V., White M., Yang X.-J., Zhao Y.;
RT "Substrate and functional diversity of lysine acetylation revealed by
RT a proteomics survey.";
RL Mol. Cell 23:607-618(2006).
RN [21]
RP INVOLVEMENT IN RPRGL3.
RX PubMed=17339269; DOI=10.1093/hmg/ddm017;
RA Bogdanova N., Horst J., Chlystun M., Croucher P.J., Nebel A.,
RA Bohring A., Todorova A., Schreiber S., Gerke V., Krawczak M.,
RA Markoff A.;
RT "A common haplotype of the annexin A5 (ANXA5) gene promoter is
RT associated with recurrent pregnancy loss.";
RL Hum. Mol. Genet. 16:573-578(2007).
RN [22]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [23]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-70; LYS-76; LYS-79 AND
RP LYS-97, AND MASS 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 [24]
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 [25]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
RX PubMed=2147412;
RA Huber R., Roemisch J., Paques E.-P.;
RT "The crystal and molecular structure of human annexin V, an
RT anticoagulant protein that binds to calcium and membranes.";
RL EMBO J. 9:3867-3874(1990).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
RX PubMed=2148156; DOI=10.1016/0014-5793(90)81428-Q;
RA Huber R., Schneider M., Mayr I., Roemisch J., Paques E.-P.;
RT "The calcium binding sites in human annexin V by crystal structure
RT analysis at 2.0-A resolution. Implications for membrane binding and
RT calcium channel activity.";
RL FEBS Lett. 275:15-21(1990).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
RX PubMed=1311770; DOI=10.1016/0022-2836(92)90984-R;
RA Huber R., Berendes R., Burger A., Schneider M., Karshikov A.,
RA Luecke H., Roemisch J., Paques E.-P.;
RT "Crystal and molecular structure of human annexin V after refinement.
RT Implications for structure, membrane binding and ion channel formation
RT of the annexin family of proteins.";
RL J. Mol. Biol. 223:683-704(1992).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS).
RX PubMed=9398511; DOI=10.1006/jmbi.1997.1375;
RA Kaneko N., Ago H., Matsuda R., Inagaki E., Miyano M.;
RT "Crystal structure of annexin V with its ligand K-201 as a calcium
RT channel activity inhibitor.";
RL J. Mol. Biol. 274:16-20(1997).
RN [29]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
RX PubMed=9435213; DOI=10.1073/pnas.95.2.455;
RA Budisa N., Minks C., Medrano F.J., Lutz J., Huber R., Moroder L.;
RT "Residue-specific bioincorporation of non-natural, biologically active
RT amino acids into proteins as possible drug carriers: structure and
RT stability of the per-thiaproline mutant of annexin V.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:455-459(1998).
CC -!- FUNCTION: This protein is an anticoagulant protein that acts as an
CC indirect inhibitor of the thromboplastin-specific complex, which
CC is involved in the blood coagulation cascade.
CC -!- SUBUNIT: Monomer. Binds ATRX and EIF5B (By similarity). Interacts
CC with hepatitis B virus (HBV).
CC -!- DOMAIN: A pair of annexin repeats may form one binding site for
CC calcium and phospholipid.
CC -!- DISEASE: Pregnancy loss, recurrent, 3 (RPRGL3) [MIM:614391]: A
CC common complication of pregnancy, resulting in spontaneous
CC abortion before the fetus has reached viability. The term includes
CC all miscarriages from the time of conception until 24 weeks of
CC gestation. Recurrent pregnancy loss is defined as 3 or more
CC consecutive spontaneous abortions. Note=Disease susceptibility is
CC associated with variations affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the annexin family.
CC -!- SIMILARITY: Contains 4 annexin repeats.
CC -!- WEB RESOURCE: Name=R&D; Systems' cytokine source book: Annexin V;
CC URL="http://www.rndsystems.com/molecule_detail.aspx?m=1063";
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; M18366; AAA35570.1; -; mRNA.
DR EMBL; D00172; BAA00122.1; -; mRNA.
DR EMBL; X12454; CAA30985.1; -; mRNA.
DR EMBL; J03745; AAA52386.1; -; mRNA.
DR EMBL; M21731; AAA36166.1; -; mRNA.
DR EMBL; M19384; AAB59545.1; -; mRNA.
DR EMBL; U01691; AAB40047.1; -; Genomic_DNA.
DR EMBL; U01681; AAB40047.1; JOINED; Genomic_DNA.
DR EMBL; U01682; AAB40047.1; JOINED; Genomic_DNA.
DR EMBL; U01683; AAB40047.1; JOINED; Genomic_DNA.
DR EMBL; U01685; AAB40047.1; JOINED; Genomic_DNA.
DR EMBL; U01686; AAB40047.1; JOINED; Genomic_DNA.
DR EMBL; U01687; AAB40047.1; JOINED; Genomic_DNA.
DR EMBL; U01689; AAB40047.1; JOINED; Genomic_DNA.
DR EMBL; U01690; AAB40047.1; JOINED; Genomic_DNA.
DR EMBL; U05770; AAB60648.1; -; Genomic_DNA.
DR EMBL; U05760; AAB60648.1; JOINED; Genomic_DNA.
DR EMBL; U05761; AAB60648.1; JOINED; Genomic_DNA.
DR EMBL; U05762; AAB60648.1; JOINED; Genomic_DNA.
DR EMBL; U05764; AAB60648.1; JOINED; Genomic_DNA.
DR EMBL; U05765; AAB60648.1; JOINED; Genomic_DNA.
DR EMBL; U05766; AAB60648.1; JOINED; Genomic_DNA.
DR EMBL; U05767; AAB60648.1; JOINED; Genomic_DNA.
DR EMBL; U05768; AAB60648.1; JOINED; Genomic_DNA.
DR EMBL; U05769; AAB60648.1; JOINED; Genomic_DNA.
DR EMBL; AK312644; BAG35528.1; -; mRNA.
DR EMBL; CR536522; CAG38759.1; -; mRNA.
DR EMBL; CR541842; CAG46640.1; -; mRNA.
DR EMBL; AC096730; AAY40954.1; -; Genomic_DNA.
DR EMBL; CH471056; EAX05257.1; -; Genomic_DNA.
DR EMBL; CH471056; EAX05258.1; -; Genomic_DNA.
DR EMBL; BC001429; AAH01429.1; -; mRNA.
DR EMBL; BC004993; AAH04993.1; -; mRNA.
DR EMBL; BC012804; AAH12804.1; -; mRNA.
DR EMBL; BC012822; AAH12822.1; -; mRNA.
DR EMBL; BC018671; AAH18671.1; -; mRNA.
DR PIR; D29250; AQHUP.
DR RefSeq; NP_001145.1; NM_001154.3.
DR UniGene; Hs.480653; -.
DR PDB; 1ANW; X-ray; 2.40 A; A/B=2-319.
DR PDB; 1ANX; X-ray; 1.90 A; A/B/C=2-319.
DR PDB; 1AVH; X-ray; 2.30 A; A/B=1-320.
DR PDB; 1AVR; X-ray; 2.30 A; A=1-320.
DR PDB; 1HAK; X-ray; 3.00 A; A/B=1-320.
DR PDB; 1HVD; X-ray; 2.00 A; A=2-319.
DR PDB; 1HVE; X-ray; 2.30 A; A=2-319.
DR PDB; 1HVF; X-ray; 2.00 A; A=2-319.
DR PDB; 1HVG; X-ray; 3.00 A; A=2-319.
DR PDB; 1SAV; X-ray; 2.50 A; A=1-320.
DR PDB; 2XO2; X-ray; 2.80 A; A=2-320.
DR PDB; 2XO3; X-ray; 2.30 A; A=1-320.
DR PDBsum; 1ANW; -.
DR PDBsum; 1ANX; -.
DR PDBsum; 1AVH; -.
DR PDBsum; 1AVR; -.
DR PDBsum; 1HAK; -.
DR PDBsum; 1HVD; -.
DR PDBsum; 1HVE; -.
DR PDBsum; 1HVF; -.
DR PDBsum; 1HVG; -.
DR PDBsum; 1SAV; -.
DR PDBsum; 2XO2; -.
DR PDBsum; 2XO3; -.
DR ProteinModelPortal; P08758; -.
DR SMR; P08758; 3-318.
DR IntAct; P08758; 16.
DR MINT; MINT-1382250; -.
DR STRING; 9606.ENSP00000296511; -.
DR PhosphoSite; P08758; -.
DR DMDM; 113960; -.
DR OGP; P08758; -.
DR REPRODUCTION-2DPAGE; IPI00329801; -.
DR REPRODUCTION-2DPAGE; P08758; -.
DR PaxDb; P08758; -.
DR PeptideAtlas; P08758; -.
DR PRIDE; P08758; -.
DR DNASU; 308; -.
DR Ensembl; ENST00000296511; ENSP00000296511; ENSG00000164111.
DR GeneID; 308; -.
DR KEGG; hsa:308; -.
DR UCSC; uc003idu.4; human.
DR CTD; 308; -.
DR GeneCards; GC04M122589; -.
DR HGNC; HGNC:543; ANXA5.
DR HPA; CAB003677; -.
DR MIM; 131230; gene.
DR MIM; 614391; phenotype.
DR neXtProt; NX_P08758; -.
DR PharmGKB; PA24833; -.
DR eggNOG; NOG281174; -.
DR HOGENOM; HOG000158803; -.
DR HOVERGEN; HBG061815; -.
DR InParanoid; P08758; -.
DR KO; K16646; -.
DR OMA; KVFDAYM; -.
DR OrthoDB; EOG74XS72; -.
DR PhylomeDB; P08758; -.
DR SignaLink; P08758; -.
DR ChiTaRS; ANXA5; human.
DR EvolutionaryTrace; P08758; -.
DR GeneWiki; Annexin_A5; -.
DR GenomeRNAi; 308; -.
DR NextBio; 1243; -.
DR PRO; PR:P08758; -.
DR ArrayExpress; P08758; -.
DR Bgee; P08758; -.
DR CleanEx; HS_ANXA5; -.
DR Genevestigator; P08758; -.
DR GO; GO:0005737; C:cytoplasm; TAS:UniProtKB.
DR GO; GO:0072563; C:endothelial microparticle; IEA:Ensembl.
DR GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl.
DR GO; GO:0070062; C:extracellular vesicular exosome; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0005544; F:calcium-dependent phospholipid binding; IDA:UniProtKB.
DR GO; GO:0004859; F:phospholipase inhibitor activity; TAS:ProtInc.
DR GO; GO:0007596; P:blood coagulation; IEA:UniProtKB-KW.
DR GO; GO:0043066; P:negative regulation of apoptotic process; TAS:UniProtKB.
DR GO; GO:0050819; P:negative regulation of coagulation; IEA:InterPro.
DR GO; GO:0010033; P:response to organic substance; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; TAS: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; IPR015473; Annexins_V.
DR InterPro; IPR002392; AnnexinV.
DR PANTHER; PTHR10502:SF26; PTHR10502:SF26; 1.
DR Pfam; PF00191; Annexin; 4.
DR PRINTS; PR00196; ANNEXIN.
DR PRINTS; PR00201; ANNEXINV.
DR SMART; SM00335; ANX; 4.
DR PROSITE; PS00223; ANNEXIN; 4.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Annexin; Blood coagulation; Calcium;
KW Calcium/phospholipid-binding; Complete proteome;
KW Direct protein sequencing; Hemostasis; Reference proteome; Repeat.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 320 Annexin A5.
FT /FTId=PRO_0000067487.
FT REPEAT 24 84 Annexin 1.
FT REPEAT 96 156 Annexin 2.
FT REPEAT 180 240 Annexin 3.
FT REPEAT 255 315 Annexin 4.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 70 70 N6-acetyllysine.
FT MOD_RES 76 76 N6-acetyllysine.
FT MOD_RES 79 79 N6-acetyllysine.
FT MOD_RES 97 97 N6-acetyllysine.
FT MOD_RES 101 101 N6-acetyllysine.
FT CONFLICT 135 135 S -> L (in Ref. 10; CAG38759).
FT CONFLICT 279 279 I -> T (in Ref. 13; AAH18671).
FT HELIX 17 28
FT STRAND 29 32
FT HELIX 35 43
FT HELIX 47 61
FT HELIX 65 72
FT HELIX 75 85
FT HELIX 88 100
FT STRAND 102 104
FT HELIX 107 116
FT HELIX 119 133
FT HELIX 137 144
FT HELIX 147 157
FT HELIX 169 182
FT TURN 183 185
FT STRAND 186 188
FT HELIX 191 200
FT HELIX 203 217
FT HELIX 221 228
FT HELIX 231 245
FT HELIX 247 256
FT HELIX 257 259
FT STRAND 260 263
FT HELIX 266 276
FT TURN 277 280
FT HELIX 281 290
FT STRAND 292 294
FT HELIX 296 303
FT HELIX 306 316
SQ SEQUENCE 320 AA; 35937 MW; 45E14E3964BA4D1A CRC64;
MAQVLRGTVT DFPGFDERAD AETLRKAMKG LGTDEESILT LLTSRSNAQR QEISAAFKTL
FGRDLLDDLK SELTGKFEKL IVALMKPSRL YDAYELKHAL KGAGTNEKVL TEIIASRTPE
ELRAIKQVYE EEYGSSLEDD VVGDTSGYYQ RMLVVLLQAN RDPDAGIDEA QVEQDAQALF
QAGELKWGTD EEKFITIFGT RSVSHLRKVF DKYMTISGFQ IEETIDRETS GNLEQLLLAV
VKSIRSIPAY LAETLYYAMK GAGTDDHTLI RVMVSRSEID LFNIRKEFRK NFATSLYSMI
KGDTSGDYKK ALLLLCGEDD
//
ID ANXA5_HUMAN Reviewed; 320 AA.
AC P08758; D3DNW7; Q6FHB3; Q6FI16; Q8WV69; Q9UDH9;
DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 166.
DE RecName: Full=Annexin A5;
DE AltName: Full=Anchorin CII;
DE AltName: Full=Annexin V;
DE AltName: Full=Annexin-5;
DE AltName: Full=Calphobindin I;
DE Short=CBP-I;
DE AltName: Full=Endonexin II;
DE AltName: Full=Lipocortin V;
DE AltName: Full=Placental anticoagulant protein 4;
DE Short=PP4;
DE AltName: Full=Placental anticoagulant protein I;
DE Short=PAP-I;
DE AltName: Full=Thromboplastin inhibitor;
DE AltName: Full=Vascular anticoagulant-alpha;
DE Short=VAC-alpha;
GN Name=ANXA5; Synonyms=ANX5, ENX2, PP4;
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=2964863; DOI=10.1021/bi00399a011;
RA Funakoshi T., Hendrickson L.E., McMullen B.A., Fujikawa K.;
RT "Primary structure of human placental anticoagulant protein.";
RL Biochemistry 26:8087-8092(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 2-320.
RX PubMed=2963810;
RA Iwasaki A., Suda M., Nakao H., Nagoya T., Saino Y., Arai K.,
RA Mizoguchi T., Sato F., Yoshizaki H., Hirata M., Miyata T., Shidara Y.,
RA Murata M., Maki M.;
RT "Structure and expression of cDNA for an inhibitor of blood
RT coagulation isolated from human placenta: a new lipocortin-like
RT protein.";
RL J. Biochem. 102:1261-1273(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=2455636; DOI=10.1111/j.1432-1033.1988.tb14139.x;
RA Maurer-Fogy I., Reutelingsperger C.P.M., Pieters J., Bodo G.,
RA Stratowa C., Hauptmann R.;
RT "Cloning and expression of cDNA for human vascular anticoagulant, a
RT Ca2+-dependent phospholipid-binding protein.";
RL Eur. J. Biochem. 174:585-592(1988).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2967291;
RA Kaplan R., Jaye M., Burgess W.H., Schlaepfer D.D., Haigler H.T.;
RT "Cloning and expression of cDNA for human endonexin II, a Ca2+ and
RT phospholipid binding protein.";
RL J. Biol. Chem. 263:8037-8043(1988).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2968983;
RA Pepinsky R.B., Tizard R., Mattaliano R.J., Sinclair L.K., Miller G.T.,
RA Browning J.L., Chow E.P., Burne C., Huang K.-S., Pratt D., Wachter L.,
RA Hession C., Frey A.Z., Wallner B.P.;
RT "Five distinct calcium and phospholipid binding proteins share
RT homology with lipocortin I.";
RL J. Biol. Chem. 263:10799-10811(1988).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2967495; DOI=10.1073/pnas.85.11.3708;
RA Grundmann U., Abel K.-J., Bohn H., Loebermann H., Lottspeich F.,
RA Kuepper H.;
RT "Characterization of cDNA encoding human placental anticoagulant
RT protein (PP4): homology with the lipocortin family.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:3708-3712(1988).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Lung;
RX PubMed=7958998; DOI=10.1016/0378-1119(94)90157-0;
RA Fernandez M.-P., Morgan R.O., Fernandez M.R., Carcedo M.-T.;
RT "The gene encoding human annexin V has a TATA-less promoter with a
RT high G+C content.";
RL Gene 149:253-260(1994).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8034319; DOI=10.1006/geno.1994.1201;
RA Cookson B.T., Engelhardt S., Smith C., Bamford H.A., Prochazka M.,
RA Tait J.F.;
RT "Organization of the human annexin V (ANX5) gene.";
RL Genomics 20:463-467(1994).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Neuroblastoma;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S.,
RA Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W.,
RA Korn B., Zuo D., Hu Y., LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [13]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Muscle, Ovary, and Skin;
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 [14]
RP PARTIAL PROTEIN SEQUENCE.
RX PubMed=2532007;
RA Rothhut R., Comera C., Cortial S., Haumont P.-Y., Diep Le K.H.,
RA Cavadore J.-C., Conard J., Russo-Marie F., Lederer F.;
RT "A 32 kDa lipocortin from human mononuclear cells appears to be
RT identical with the placental inhibitor of blood coagulation.";
RL Biochem. J. 263:929-935(1989).
RN [15]
RP PROTEIN SEQUENCE OF 7-18; 30-45; 187-201 AND 277-286, AND MASS
RP SPECTROMETRY.
RC TISSUE=Melanoma;
RA Quadroni M., Potts A., Barblan J., Bienvenut W.V.;
RL Submitted (JAN-2005) to UniProtKB.
RN [16]
RP PROTEIN SEQUENCE OF 21-31; 93-108; 176-188 AND 304-319, AND
RP INTERACTION WITH HBV.
RX PubMed=8249278; DOI=10.1006/viro.1993.1628;
RA Hertogs K., Leenders W.P., Depla E., De Bruin W.C., Meheus L.,
RA Raymackers J., Moshage H., Yap S.H.;
RT "Endonexin II, present on human liver plasma membranes, is a specific
RT binding protein of small hepatitis B virus (HBV) envelope protein.";
RL Virology 197:549-557(1993).
RN [17]
RP PROTEIN SEQUENCE OF 86-131; 259-297 AND 300-320.
RX PubMed=2957692; DOI=10.1073/pnas.84.17.6078;
RA Schlaepfer D.D., Mehlman T., Burgess W.H., Haigler H.T.;
RT "Structural and functional characterization of endonexin II, a
RT calcium- and phospholipid-binding protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:6078-6082(1987).
RN [18]
RP PROTEIN SEQUENCE OF 85-93.
RC TISSUE=Placenta;
RX PubMed=2974032;
RA Ahn N.G., Teller D.C., Bienkowski M.J., McMullen B.A., Lipkin E.W.,
RA de Haen C.;
RT "Sedimentation equilibrium analysis of five lipocortin-related
RT phospholipase A2 inhibitors from human placenta. Evidence against a
RT mechanistically relevant association between enzyme and inhibitor.";
RL J. Biol. Chem. 263:18657-18663(1988).
RN [19]
RP PROTEIN SEQUENCE OF 152-161 AND 246-260.
RC TISSUE=Adipocyte;
RX PubMed=15242332; DOI=10.1042/BJ20040647;
RA Aboulaich N., Vainonen J.P., Stralfors P., Vener A.V.;
RT "Vectorial proteomics reveal targeting, phosphorylation and specific
RT fragmentation of polymerase I and transcript release factor (PTRF) at
RT the surface of caveolae in human adipocytes.";
RL Biochem. J. 383:237-248(2004).
RN [20]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-101, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=16916647; DOI=10.1016/j.molcel.2006.06.026;
RA Kim S.C., Sprung R., Chen Y., Xu Y., Ball H., Pei J., Cheng T.,
RA Kho Y., Xiao H., Xiao L., Grishin N.V., White M., Yang X.-J., Zhao Y.;
RT "Substrate and functional diversity of lysine acetylation revealed by
RT a proteomics survey.";
RL Mol. Cell 23:607-618(2006).
RN [21]
RP INVOLVEMENT IN RPRGL3.
RX PubMed=17339269; DOI=10.1093/hmg/ddm017;
RA Bogdanova N., Horst J., Chlystun M., Croucher P.J., Nebel A.,
RA Bohring A., Todorova A., Schreiber S., Gerke V., Krawczak M.,
RA Markoff A.;
RT "A common haplotype of the annexin A5 (ANXA5) gene promoter is
RT associated with recurrent pregnancy loss.";
RL Hum. Mol. Genet. 16:573-578(2007).
RN [22]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [23]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-70; LYS-76; LYS-79 AND
RP LYS-97, AND MASS 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 [24]
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 [25]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
RX PubMed=2147412;
RA Huber R., Roemisch J., Paques E.-P.;
RT "The crystal and molecular structure of human annexin V, an
RT anticoagulant protein that binds to calcium and membranes.";
RL EMBO J. 9:3867-3874(1990).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
RX PubMed=2148156; DOI=10.1016/0014-5793(90)81428-Q;
RA Huber R., Schneider M., Mayr I., Roemisch J., Paques E.-P.;
RT "The calcium binding sites in human annexin V by crystal structure
RT analysis at 2.0-A resolution. Implications for membrane binding and
RT calcium channel activity.";
RL FEBS Lett. 275:15-21(1990).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
RX PubMed=1311770; DOI=10.1016/0022-2836(92)90984-R;
RA Huber R., Berendes R., Burger A., Schneider M., Karshikov A.,
RA Luecke H., Roemisch J., Paques E.-P.;
RT "Crystal and molecular structure of human annexin V after refinement.
RT Implications for structure, membrane binding and ion channel formation
RT of the annexin family of proteins.";
RL J. Mol. Biol. 223:683-704(1992).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS).
RX PubMed=9398511; DOI=10.1006/jmbi.1997.1375;
RA Kaneko N., Ago H., Matsuda R., Inagaki E., Miyano M.;
RT "Crystal structure of annexin V with its ligand K-201 as a calcium
RT channel activity inhibitor.";
RL J. Mol. Biol. 274:16-20(1997).
RN [29]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
RX PubMed=9435213; DOI=10.1073/pnas.95.2.455;
RA Budisa N., Minks C., Medrano F.J., Lutz J., Huber R., Moroder L.;
RT "Residue-specific bioincorporation of non-natural, biologically active
RT amino acids into proteins as possible drug carriers: structure and
RT stability of the per-thiaproline mutant of annexin V.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:455-459(1998).
CC -!- FUNCTION: This protein is an anticoagulant protein that acts as an
CC indirect inhibitor of the thromboplastin-specific complex, which
CC is involved in the blood coagulation cascade.
CC -!- SUBUNIT: Monomer. Binds ATRX and EIF5B (By similarity). Interacts
CC with hepatitis B virus (HBV).
CC -!- DOMAIN: A pair of annexin repeats may form one binding site for
CC calcium and phospholipid.
CC -!- DISEASE: Pregnancy loss, recurrent, 3 (RPRGL3) [MIM:614391]: A
CC common complication of pregnancy, resulting in spontaneous
CC abortion before the fetus has reached viability. The term includes
CC all miscarriages from the time of conception until 24 weeks of
CC gestation. Recurrent pregnancy loss is defined as 3 or more
CC consecutive spontaneous abortions. Note=Disease susceptibility is
CC associated with variations affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the annexin family.
CC -!- SIMILARITY: Contains 4 annexin repeats.
CC -!- WEB RESOURCE: Name=R&D; Systems' cytokine source book: Annexin V;
CC URL="http://www.rndsystems.com/molecule_detail.aspx?m=1063";
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; M18366; AAA35570.1; -; mRNA.
DR EMBL; D00172; BAA00122.1; -; mRNA.
DR EMBL; X12454; CAA30985.1; -; mRNA.
DR EMBL; J03745; AAA52386.1; -; mRNA.
DR EMBL; M21731; AAA36166.1; -; mRNA.
DR EMBL; M19384; AAB59545.1; -; mRNA.
DR EMBL; U01691; AAB40047.1; -; Genomic_DNA.
DR EMBL; U01681; AAB40047.1; JOINED; Genomic_DNA.
DR EMBL; U01682; AAB40047.1; JOINED; Genomic_DNA.
DR EMBL; U01683; AAB40047.1; JOINED; Genomic_DNA.
DR EMBL; U01685; AAB40047.1; JOINED; Genomic_DNA.
DR EMBL; U01686; AAB40047.1; JOINED; Genomic_DNA.
DR EMBL; U01687; AAB40047.1; JOINED; Genomic_DNA.
DR EMBL; U01689; AAB40047.1; JOINED; Genomic_DNA.
DR EMBL; U01690; AAB40047.1; JOINED; Genomic_DNA.
DR EMBL; U05770; AAB60648.1; -; Genomic_DNA.
DR EMBL; U05760; AAB60648.1; JOINED; Genomic_DNA.
DR EMBL; U05761; AAB60648.1; JOINED; Genomic_DNA.
DR EMBL; U05762; AAB60648.1; JOINED; Genomic_DNA.
DR EMBL; U05764; AAB60648.1; JOINED; Genomic_DNA.
DR EMBL; U05765; AAB60648.1; JOINED; Genomic_DNA.
DR EMBL; U05766; AAB60648.1; JOINED; Genomic_DNA.
DR EMBL; U05767; AAB60648.1; JOINED; Genomic_DNA.
DR EMBL; U05768; AAB60648.1; JOINED; Genomic_DNA.
DR EMBL; U05769; AAB60648.1; JOINED; Genomic_DNA.
DR EMBL; AK312644; BAG35528.1; -; mRNA.
DR EMBL; CR536522; CAG38759.1; -; mRNA.
DR EMBL; CR541842; CAG46640.1; -; mRNA.
DR EMBL; AC096730; AAY40954.1; -; Genomic_DNA.
DR EMBL; CH471056; EAX05257.1; -; Genomic_DNA.
DR EMBL; CH471056; EAX05258.1; -; Genomic_DNA.
DR EMBL; BC001429; AAH01429.1; -; mRNA.
DR EMBL; BC004993; AAH04993.1; -; mRNA.
DR EMBL; BC012804; AAH12804.1; -; mRNA.
DR EMBL; BC012822; AAH12822.1; -; mRNA.
DR EMBL; BC018671; AAH18671.1; -; mRNA.
DR PIR; D29250; AQHUP.
DR RefSeq; NP_001145.1; NM_001154.3.
DR UniGene; Hs.480653; -.
DR PDB; 1ANW; X-ray; 2.40 A; A/B=2-319.
DR PDB; 1ANX; X-ray; 1.90 A; A/B/C=2-319.
DR PDB; 1AVH; X-ray; 2.30 A; A/B=1-320.
DR PDB; 1AVR; X-ray; 2.30 A; A=1-320.
DR PDB; 1HAK; X-ray; 3.00 A; A/B=1-320.
DR PDB; 1HVD; X-ray; 2.00 A; A=2-319.
DR PDB; 1HVE; X-ray; 2.30 A; A=2-319.
DR PDB; 1HVF; X-ray; 2.00 A; A=2-319.
DR PDB; 1HVG; X-ray; 3.00 A; A=2-319.
DR PDB; 1SAV; X-ray; 2.50 A; A=1-320.
DR PDB; 2XO2; X-ray; 2.80 A; A=2-320.
DR PDB; 2XO3; X-ray; 2.30 A; A=1-320.
DR PDBsum; 1ANW; -.
DR PDBsum; 1ANX; -.
DR PDBsum; 1AVH; -.
DR PDBsum; 1AVR; -.
DR PDBsum; 1HAK; -.
DR PDBsum; 1HVD; -.
DR PDBsum; 1HVE; -.
DR PDBsum; 1HVF; -.
DR PDBsum; 1HVG; -.
DR PDBsum; 1SAV; -.
DR PDBsum; 2XO2; -.
DR PDBsum; 2XO3; -.
DR ProteinModelPortal; P08758; -.
DR SMR; P08758; 3-318.
DR IntAct; P08758; 16.
DR MINT; MINT-1382250; -.
DR STRING; 9606.ENSP00000296511; -.
DR PhosphoSite; P08758; -.
DR DMDM; 113960; -.
DR OGP; P08758; -.
DR REPRODUCTION-2DPAGE; IPI00329801; -.
DR REPRODUCTION-2DPAGE; P08758; -.
DR PaxDb; P08758; -.
DR PeptideAtlas; P08758; -.
DR PRIDE; P08758; -.
DR DNASU; 308; -.
DR Ensembl; ENST00000296511; ENSP00000296511; ENSG00000164111.
DR GeneID; 308; -.
DR KEGG; hsa:308; -.
DR UCSC; uc003idu.4; human.
DR CTD; 308; -.
DR GeneCards; GC04M122589; -.
DR HGNC; HGNC:543; ANXA5.
DR HPA; CAB003677; -.
DR MIM; 131230; gene.
DR MIM; 614391; phenotype.
DR neXtProt; NX_P08758; -.
DR PharmGKB; PA24833; -.
DR eggNOG; NOG281174; -.
DR HOGENOM; HOG000158803; -.
DR HOVERGEN; HBG061815; -.
DR InParanoid; P08758; -.
DR KO; K16646; -.
DR OMA; KVFDAYM; -.
DR OrthoDB; EOG74XS72; -.
DR PhylomeDB; P08758; -.
DR SignaLink; P08758; -.
DR ChiTaRS; ANXA5; human.
DR EvolutionaryTrace; P08758; -.
DR GeneWiki; Annexin_A5; -.
DR GenomeRNAi; 308; -.
DR NextBio; 1243; -.
DR PRO; PR:P08758; -.
DR ArrayExpress; P08758; -.
DR Bgee; P08758; -.
DR CleanEx; HS_ANXA5; -.
DR Genevestigator; P08758; -.
DR GO; GO:0005737; C:cytoplasm; TAS:UniProtKB.
DR GO; GO:0072563; C:endothelial microparticle; IEA:Ensembl.
DR GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl.
DR GO; GO:0070062; C:extracellular vesicular exosome; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0005544; F:calcium-dependent phospholipid binding; IDA:UniProtKB.
DR GO; GO:0004859; F:phospholipase inhibitor activity; TAS:ProtInc.
DR GO; GO:0007596; P:blood coagulation; IEA:UniProtKB-KW.
DR GO; GO:0043066; P:negative regulation of apoptotic process; TAS:UniProtKB.
DR GO; GO:0050819; P:negative regulation of coagulation; IEA:InterPro.
DR GO; GO:0010033; P:response to organic substance; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; TAS: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; IPR015473; Annexins_V.
DR InterPro; IPR002392; AnnexinV.
DR PANTHER; PTHR10502:SF26; PTHR10502:SF26; 1.
DR Pfam; PF00191; Annexin; 4.
DR PRINTS; PR00196; ANNEXIN.
DR PRINTS; PR00201; ANNEXINV.
DR SMART; SM00335; ANX; 4.
DR PROSITE; PS00223; ANNEXIN; 4.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Annexin; Blood coagulation; Calcium;
KW Calcium/phospholipid-binding; Complete proteome;
KW Direct protein sequencing; Hemostasis; Reference proteome; Repeat.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 320 Annexin A5.
FT /FTId=PRO_0000067487.
FT REPEAT 24 84 Annexin 1.
FT REPEAT 96 156 Annexin 2.
FT REPEAT 180 240 Annexin 3.
FT REPEAT 255 315 Annexin 4.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 70 70 N6-acetyllysine.
FT MOD_RES 76 76 N6-acetyllysine.
FT MOD_RES 79 79 N6-acetyllysine.
FT MOD_RES 97 97 N6-acetyllysine.
FT MOD_RES 101 101 N6-acetyllysine.
FT CONFLICT 135 135 S -> L (in Ref. 10; CAG38759).
FT CONFLICT 279 279 I -> T (in Ref. 13; AAH18671).
FT HELIX 17 28
FT STRAND 29 32
FT HELIX 35 43
FT HELIX 47 61
FT HELIX 65 72
FT HELIX 75 85
FT HELIX 88 100
FT STRAND 102 104
FT HELIX 107 116
FT HELIX 119 133
FT HELIX 137 144
FT HELIX 147 157
FT HELIX 169 182
FT TURN 183 185
FT STRAND 186 188
FT HELIX 191 200
FT HELIX 203 217
FT HELIX 221 228
FT HELIX 231 245
FT HELIX 247 256
FT HELIX 257 259
FT STRAND 260 263
FT HELIX 266 276
FT TURN 277 280
FT HELIX 281 290
FT STRAND 292 294
FT HELIX 296 303
FT HELIX 306 316
SQ SEQUENCE 320 AA; 35937 MW; 45E14E3964BA4D1A CRC64;
MAQVLRGTVT DFPGFDERAD AETLRKAMKG LGTDEESILT LLTSRSNAQR QEISAAFKTL
FGRDLLDDLK SELTGKFEKL IVALMKPSRL YDAYELKHAL KGAGTNEKVL TEIIASRTPE
ELRAIKQVYE EEYGSSLEDD VVGDTSGYYQ RMLVVLLQAN RDPDAGIDEA QVEQDAQALF
QAGELKWGTD EEKFITIFGT RSVSHLRKVF DKYMTISGFQ IEETIDRETS GNLEQLLLAV
VKSIRSIPAY LAETLYYAMK GAGTDDHTLI RVMVSRSEID LFNIRKEFRK NFATSLYSMI
KGDTSGDYKK ALLLLCGEDD
//
MIM
131230
*RECORD*
*FIELD* NO
131230
*FIELD* TI
*131230 ANNEXIN A5; ANXA5
;;ANNEXIN V; ANX5;;
ENDONEXIN II; ENX2;;
PLACENTAL ANTICOAGULANT PROTEIN I;;
read moreVASCULAR ANTICOAGULANT-ALPHA;;
LIPOCORTIN V;;
PLACENTAL PROTEIN 4; PP4;;
ANCHORIN CII
*FIELD* TX
CLONING
PP4 is an anticoagulant protein that acts as an indirect inhibitor of
the thromboplastin-specific complex, which is involved in the blood
coagulation cascade. It has a relative molecular weight of about 35,000
and is present in placental tissue to the extent of about 50 mg per
placenta with very little secretion into the maternal bloodstream. The
PP4 cDNA encoded a protein of 320 amino acid residues. In addition to
the PP4 cDNA, Grundmann et al. (1988) identified cDNA encoding a protein
with 74% identity to PP4, which they termed PP4-X. PP4 and PP4-X belong
to the lipocortin family, as judged by their homology to lipocortin I
(151690) and calpactin I (114085). The placental anticoagulant protein
called PAP, isolated by Funakoshi et al. (1987), may be the same
protein. PP4 is also known as endonexin II.
Endonexin II is a member of the family of Ca(2+)-dependent phospholipid
binding proteins, known as annexins, which bind to the phospholipids
that are preferentially located on the cytosolic face of the plasma
membrane. Kaplan et al. (1988) cloned endonexin II cDNA and expressed it
in Escherichia coli. A single mRNA, approximately 1.6 kb long, was found
to be expressed in human cell lines and placenta. The length of the cDNA
clone was 1.59 kb. The cDNA predicted a 320-amino acid protein with a
sequence in agreement with the previously determined partial amino acid
sequence of endonexin II isolated from placenta.
MAPPING
Using a cDNA clone of endonexin II, Modi et al. (1989) assigned the
ANXA5 gene to 4q28-q31 by in situ hybridization and Southern analysis of
human-rodent cell hybrid DNAs. Tait et al. (1991) found a somewhat
different localization which overlapped with the assignment of Modi et
al. (1989). By in situ hybridization with a cDNA probe and by polymerase
chain reaction (PCR) analysis of a human/hamster hybrid cell panel, they
assigned the ANXA5 gene to 4q26-q28. The regional localization was
supported by Southern blot analysis of a human cell line with a deletion
in 4q23-q27. A compromise assignment might be 4q26-q28. Rodriguez-Garcia
et al. (1996) mapped the homologous gene to mouse chromosome 3.
GENE FUNCTION
Annexin V forms the voltage-dependent Ca(2+) channels in phospholipid
bilayers and was the first ion channel to be structurally and
functionally characterized. Demange et al. (1994) outlined data
indicating that key amino acid residues act as selectivity filters and
voltage sensors, thereby regulating the permeability of the channel pore
to ions.
Tzima et al. (2000) showed that annexin V bound to F-actin and
gamma-actin (ACTG1; 102560), but not beta-actin (ACTB; 102630), in
activated human platelets.
MOLECULAR GENETICS
In 70 German patients with recurrent pregnancy loss (RPRGL3; 614391) who
were known to carry neither factor V Leiden (612309.0001) nor a
prothrombin (176930) mutation, Bogdanova et al. (2007) analyzed the
ANXA5 gene and identified 4 consecutive nucleotide substitutions in the
promoter region that were transmitted as a joint haplotype designated
'M2' (131230.0001). Carriers of the M2 haplotype had a 2- to 4-fold
higher risk of RPRGL than noncarriers.
ANIMAL MODEL
Brachvogel et al. (2003) found that heterozygous and homozygous
Anxa5-deficient mice were born at expected mendelian ratios, were viable
and fertile, and showed no obvious phenotypic or behavioral
abnormalities.
*FIELD* AV
.0001
PREGNANCY LOSS, RECURRENT, SUSCEPTIBILITY TO, 3
ANXA5, M2 HAPLOTYPE
In 70 German patients with recurrent pregnancy loss (RPRGL3; 614391) who
were negative for factor V Leiden (612309.0001) and a known
RPRGL-related prothrombin mutation (176930.0009), Bogdanova et al.
(2007) analyzed the ANXA5 gene and identified 4 consecutive nucleotide
substitutions in the promoter region, -19G-A, 1A-C, 27T-C, and 76G-A,
that were transmitted as a joint haplotype, which they designated 'M2.'
All substitutions changed a transcription factor consensus site or
affected a nucleotide adjacent to it. Reporter gene assays revealed that
when all 4 nucleotide substitutions were present, ANXA5 promoter
activity was reduced to less than half (37% to 42%) of wildtype
activity. Carriers of the M2 haplotype had a greater than 2-fold higher
risk of RPRGL than noncarriers (odds ratio, 2.42) when using unselected
controls; when compared to women with successful pregnancies and no
previous history of pregnancy loss, carriers had an almost 4-fold higher
risk of RPRGL (odds ratio, 3.88).
*FIELD* SA
Modi et al. (1989)
*FIELD* RF
1. Bogdanova, N.; Horst, J.; Chlystun, M.; Croucher, P. J. P.; Nebel,
A.; Bohring, A.; Todorova, A.; Schreiber, S.; Gerke, V.; Krawczak,
M.; Markoff, A.: A common haplotype of the annexin A5 (ANXA5) gene
promoter is associated with recurrent pregnancy loss. Hum. Molec.
Genet. 16: 573-578, 2007.
2. Brachvogel, B.; Dikschas, J.; Moch, H.; Welzel, H.; von der Mark,
K.; Hofmann, C.; Poschl, E.: Annexin A5 is not essential for skeletal
development. Molec. Cell. Biol. 23: 2907-2913, 2003.
3. Demange, P.; Voges, D.; Benz, J.; Liemann, S.; Gottig, P.; Berendes,
R.; Burger, A.; Huber, R.: Annexin V: the key to understanding ion
selectivity and voltage regulation? Trends Biochem. Sci. 19: 272-276,
1994.
4. Funakoshi, T.; Heimark, R. L.; Hendrickson, L. E.; McMullen, B.
A.; Fujikawa, K.: Human placental anticoagulant protein: isolation
and characterization. Biochemistry 26: 5572-5578, 1987.
5. Grundmann, U.; Abel, K.-J.; Bohn, H.; Lobermann, H.; Lottspeich,
F.; Kupper, H.: Characterization of cDNA encoding human placental
anticoagulant protein (PP4): homology with the lipocortin family. Proc.
Nat. Acad. Sci. 85: 3708-3712, 1988.
6. 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.
7. Modi, W. S.; Seuanez, H.; Jaye, M.; Kaplan, R.; Haigler, H.; O'Brien,
S. J.: Chromosomal mapping of the endonexin II gene. (Abstract) Cytogenet.
Cell Genet. 51: 1046, 1989.
8. Modi, W. S.; Seuanez, H. N.; Jaye, M.; Haigler, H. J.; Kaplan,
R.; O'Brien, S. J.: The human endonexin II (ENX2) gene is located
at 4q28-q32. Cytogenet. Cell Genet. 52: 167-169, 1989.
9. Rodriguez-Garcia, M. I.; Kozak, C. A.; Morgan, R. O.; Fernandez,
M. P.: Mouse annexin V chromosomal localization, cDNA sequence conservation,
and molecular evolution. Genomics 31: 151-157, 1996.
10. Tait, J. F.; Frankenberry, D. A.; Shiang, R.; Murray, J. C.; Adler,
D. A.; Disteche, C. M.: Chromosomal localization of the human gene
for annexin V (placental anticoagulant protein I) to 4q26-q28. Cytogenet.
Cell Genet. 57: 187-192, 1991.
11. Tzima, E.; Trotter, P. J.; Orchard, M. A.; Walker, J. H.: Annexin
V relocates to the platelet cytoskeleton upon activation and binds
to a specific isoform of actin. J. Biochem. 267: 4720-4730, 2000.
*FIELD* CN
Marla J. F. O'Neill - updated: 12/13/2011
Patricia A. Hartz - updated: 10/11/2006
Patricia A. Hartz - updated: 6/7/2005
*FIELD* CD
Victor A. McKusick: 8/22/1988
*FIELD* ED
alopez: 12/13/2011
terry: 5/20/2010
mgross: 10/11/2006
wwang: 6/22/2005
terry: 6/7/2005
mgross: 9/17/1999
terry: 4/30/1999
alopez: 7/16/1997
mark: 3/11/1996
terry: 3/6/1996
carol: 10/14/1994
carol: 7/22/1993
carol: 3/26/1992
supermim: 3/16/1992
carol: 2/5/1992
carol: 6/11/1990
*RECORD*
*FIELD* NO
131230
*FIELD* TI
*131230 ANNEXIN A5; ANXA5
;;ANNEXIN V; ANX5;;
ENDONEXIN II; ENX2;;
PLACENTAL ANTICOAGULANT PROTEIN I;;
read moreVASCULAR ANTICOAGULANT-ALPHA;;
LIPOCORTIN V;;
PLACENTAL PROTEIN 4; PP4;;
ANCHORIN CII
*FIELD* TX
CLONING
PP4 is an anticoagulant protein that acts as an indirect inhibitor of
the thromboplastin-specific complex, which is involved in the blood
coagulation cascade. It has a relative molecular weight of about 35,000
and is present in placental tissue to the extent of about 50 mg per
placenta with very little secretion into the maternal bloodstream. The
PP4 cDNA encoded a protein of 320 amino acid residues. In addition to
the PP4 cDNA, Grundmann et al. (1988) identified cDNA encoding a protein
with 74% identity to PP4, which they termed PP4-X. PP4 and PP4-X belong
to the lipocortin family, as judged by their homology to lipocortin I
(151690) and calpactin I (114085). The placental anticoagulant protein
called PAP, isolated by Funakoshi et al. (1987), may be the same
protein. PP4 is also known as endonexin II.
Endonexin II is a member of the family of Ca(2+)-dependent phospholipid
binding proteins, known as annexins, which bind to the phospholipids
that are preferentially located on the cytosolic face of the plasma
membrane. Kaplan et al. (1988) cloned endonexin II cDNA and expressed it
in Escherichia coli. A single mRNA, approximately 1.6 kb long, was found
to be expressed in human cell lines and placenta. The length of the cDNA
clone was 1.59 kb. The cDNA predicted a 320-amino acid protein with a
sequence in agreement with the previously determined partial amino acid
sequence of endonexin II isolated from placenta.
MAPPING
Using a cDNA clone of endonexin II, Modi et al. (1989) assigned the
ANXA5 gene to 4q28-q31 by in situ hybridization and Southern analysis of
human-rodent cell hybrid DNAs. Tait et al. (1991) found a somewhat
different localization which overlapped with the assignment of Modi et
al. (1989). By in situ hybridization with a cDNA probe and by polymerase
chain reaction (PCR) analysis of a human/hamster hybrid cell panel, they
assigned the ANXA5 gene to 4q26-q28. The regional localization was
supported by Southern blot analysis of a human cell line with a deletion
in 4q23-q27. A compromise assignment might be 4q26-q28. Rodriguez-Garcia
et al. (1996) mapped the homologous gene to mouse chromosome 3.
GENE FUNCTION
Annexin V forms the voltage-dependent Ca(2+) channels in phospholipid
bilayers and was the first ion channel to be structurally and
functionally characterized. Demange et al. (1994) outlined data
indicating that key amino acid residues act as selectivity filters and
voltage sensors, thereby regulating the permeability of the channel pore
to ions.
Tzima et al. (2000) showed that annexin V bound to F-actin and
gamma-actin (ACTG1; 102560), but not beta-actin (ACTB; 102630), in
activated human platelets.
MOLECULAR GENETICS
In 70 German patients with recurrent pregnancy loss (RPRGL3; 614391) who
were known to carry neither factor V Leiden (612309.0001) nor a
prothrombin (176930) mutation, Bogdanova et al. (2007) analyzed the
ANXA5 gene and identified 4 consecutive nucleotide substitutions in the
promoter region that were transmitted as a joint haplotype designated
'M2' (131230.0001). Carriers of the M2 haplotype had a 2- to 4-fold
higher risk of RPRGL than noncarriers.
ANIMAL MODEL
Brachvogel et al. (2003) found that heterozygous and homozygous
Anxa5-deficient mice were born at expected mendelian ratios, were viable
and fertile, and showed no obvious phenotypic or behavioral
abnormalities.
*FIELD* AV
.0001
PREGNANCY LOSS, RECURRENT, SUSCEPTIBILITY TO, 3
ANXA5, M2 HAPLOTYPE
In 70 German patients with recurrent pregnancy loss (RPRGL3; 614391) who
were negative for factor V Leiden (612309.0001) and a known
RPRGL-related prothrombin mutation (176930.0009), Bogdanova et al.
(2007) analyzed the ANXA5 gene and identified 4 consecutive nucleotide
substitutions in the promoter region, -19G-A, 1A-C, 27T-C, and 76G-A,
that were transmitted as a joint haplotype, which they designated 'M2.'
All substitutions changed a transcription factor consensus site or
affected a nucleotide adjacent to it. Reporter gene assays revealed that
when all 4 nucleotide substitutions were present, ANXA5 promoter
activity was reduced to less than half (37% to 42%) of wildtype
activity. Carriers of the M2 haplotype had a greater than 2-fold higher
risk of RPRGL than noncarriers (odds ratio, 2.42) when using unselected
controls; when compared to women with successful pregnancies and no
previous history of pregnancy loss, carriers had an almost 4-fold higher
risk of RPRGL (odds ratio, 3.88).
*FIELD* SA
Modi et al. (1989)
*FIELD* RF
1. Bogdanova, N.; Horst, J.; Chlystun, M.; Croucher, P. J. P.; Nebel,
A.; Bohring, A.; Todorova, A.; Schreiber, S.; Gerke, V.; Krawczak,
M.; Markoff, A.: A common haplotype of the annexin A5 (ANXA5) gene
promoter is associated with recurrent pregnancy loss. Hum. Molec.
Genet. 16: 573-578, 2007.
2. Brachvogel, B.; Dikschas, J.; Moch, H.; Welzel, H.; von der Mark,
K.; Hofmann, C.; Poschl, E.: Annexin A5 is not essential for skeletal
development. Molec. Cell. Biol. 23: 2907-2913, 2003.
3. Demange, P.; Voges, D.; Benz, J.; Liemann, S.; Gottig, P.; Berendes,
R.; Burger, A.; Huber, R.: Annexin V: the key to understanding ion
selectivity and voltage regulation? Trends Biochem. Sci. 19: 272-276,
1994.
4. Funakoshi, T.; Heimark, R. L.; Hendrickson, L. E.; McMullen, B.
A.; Fujikawa, K.: Human placental anticoagulant protein: isolation
and characterization. Biochemistry 26: 5572-5578, 1987.
5. Grundmann, U.; Abel, K.-J.; Bohn, H.; Lobermann, H.; Lottspeich,
F.; Kupper, H.: Characterization of cDNA encoding human placental
anticoagulant protein (PP4): homology with the lipocortin family. Proc.
Nat. Acad. Sci. 85: 3708-3712, 1988.
6. 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.
7. Modi, W. S.; Seuanez, H.; Jaye, M.; Kaplan, R.; Haigler, H.; O'Brien,
S. J.: Chromosomal mapping of the endonexin II gene. (Abstract) Cytogenet.
Cell Genet. 51: 1046, 1989.
8. Modi, W. S.; Seuanez, H. N.; Jaye, M.; Haigler, H. J.; Kaplan,
R.; O'Brien, S. J.: The human endonexin II (ENX2) gene is located
at 4q28-q32. Cytogenet. Cell Genet. 52: 167-169, 1989.
9. Rodriguez-Garcia, M. I.; Kozak, C. A.; Morgan, R. O.; Fernandez,
M. P.: Mouse annexin V chromosomal localization, cDNA sequence conservation,
and molecular evolution. Genomics 31: 151-157, 1996.
10. Tait, J. F.; Frankenberry, D. A.; Shiang, R.; Murray, J. C.; Adler,
D. A.; Disteche, C. M.: Chromosomal localization of the human gene
for annexin V (placental anticoagulant protein I) to 4q26-q28. Cytogenet.
Cell Genet. 57: 187-192, 1991.
11. Tzima, E.; Trotter, P. J.; Orchard, M. A.; Walker, J. H.: Annexin
V relocates to the platelet cytoskeleton upon activation and binds
to a specific isoform of actin. J. Biochem. 267: 4720-4730, 2000.
*FIELD* CN
Marla J. F. O'Neill - updated: 12/13/2011
Patricia A. Hartz - updated: 10/11/2006
Patricia A. Hartz - updated: 6/7/2005
*FIELD* CD
Victor A. McKusick: 8/22/1988
*FIELD* ED
alopez: 12/13/2011
terry: 5/20/2010
mgross: 10/11/2006
wwang: 6/22/2005
terry: 6/7/2005
mgross: 9/17/1999
terry: 4/30/1999
alopez: 7/16/1997
mark: 3/11/1996
terry: 3/6/1996
carol: 10/14/1994
carol: 7/22/1993
carol: 3/26/1992
supermim: 3/16/1992
carol: 2/5/1992
carol: 6/11/1990
MIM
614391
*RECORD*
*FIELD* NO
614391
*FIELD* TI
#614391 PREGNANCY LOSS, RECURRENT, SUSCEPTIBILITY TO, 3; RPRGL3
*FIELD* TX
A number sign (#) is used with this entry because of evidence that
read moresusceptibility to recurrent pregnancy loss can be caused by variation in
the ANXA5 gene (131230) on chromosome 4q26-q28.
For a discussion of genetic heterogeneity of susceptibility to recurrent
pregnancy loss, see RPRGL1 (614389).
DESCRIPTION
Miscarriage, the commonest complication of pregnancy, is the spontaneous
loss of a pregnancy before the fetus has reached viability. The term
therefore includes all pregnancy losses from the time of conception
until 24 weeks of gestation. Recurrent miscarriage, defined as 3 or more
consecutive pregnancy losses, affects about 1% of couples; when defined
as 2 or more losses, the scale of the problem increases to 5% of all
couples trying to conceive (summary by Rai and Regan, 2006).
Pregnancy losses have traditionally been designated 'spontaneous
abortions' if they occur before 20 weeks' gestation and 'stillbirths' if
they occur after 20 weeks. Subtypes of spontaneous abortions can be
further distinguished on the basis of embryonic development and include
anembryonic loss in the first 5 weeks after conception (so-called
'blighted ovum'), embryonic loss from 6 to 9 weeks' gestation, and fetal
loss from 10 weeks' gestation through the remainder of the pregnancy.
These distinctions are important because the causes of pregnancy loss
vary over gestational ages, with anembryonic losses being more likely to
be associated with chromosomal abnormalities, for example. Possible
etiologies for recurrent pregnancy loss include uterine anatomic
abnormalities, cytogenetic abnormalities in the parents or fetus, single
gene disorders, thrombophilic conditions, and immunologic or endocrine
factors as well as environmental or infectious agents (summary by Warren
and Silver, 2008).
MOLECULAR GENETICS
In 70 German patients with recurrent pregnancy loss (RPRGL) who were
known to carry neither factor V Leiden (612309.0001) nor the 20210G-A
prothrombin mutation (176930.0009), Bogdanova et al. (2007) analyzed the
gene encoding the placental anticoagulant protein annexin A5 (ANXA5;
131230). They identified 4 consecutive nucleotide substitutions in the
promoter region that were transmitted as a joint haplotype that they
designated 'M2' (131230.0001). Carriers of the M2 haplotype had a
greater than 2-fold higher risk of RPRGL than noncarriers (odds ratio,
2.42) when using unselected controls; when compared to women with
successful pregnancies and no previous history of pregnancy loss,
carriers had an almost 4-fold higher risk of RPRGL (odds ratio, 3.88).
*FIELD* RF
1. Bogdanova, N.; Horst, J.; Chlystun, M.; Croucher, P. J. P.; Nebel,
A.; Bohring, A.; Todorova, A.; Schreiber, S.; Gerke, V.; Krawczak,
M.; Markoff, A.: A common haplotype of the annexin A5 (ANXA5) gene
promoter is associated with recurrent pregnancy loss. Hum. Molec.
Genet. 16: 573-578, 2007.
2. Rai, R.; Regan, L.: Recurrent miscarriage. Lancet 368: 601-611,
2006.
3. Warren, J. E.; Silver, R. M.: Genetics of pregnancy loss. Clin.
Obstet. Gynec. 51: 84-95, 2008.
*FIELD* CS
INHERITANCE:
Autosomal dominant
GENITOURINARY:
[Internal genitalia, female];
Spontaneous abortion, recurrent
MOLECULAR BASIS:
Caused by mutation in the annexin A5 gene (ANXA5, 131230.0001)
*FIELD* CD
Marla J. F. O'Neill: 12/13/2011
*FIELD* ED
joanna: 12/13/2011
*FIELD* CD
Marla J. F. O'Neill: 12/12/2011
*FIELD* ED
alopez: 12/13/2011
*RECORD*
*FIELD* NO
614391
*FIELD* TI
#614391 PREGNANCY LOSS, RECURRENT, SUSCEPTIBILITY TO, 3; RPRGL3
*FIELD* TX
A number sign (#) is used with this entry because of evidence that
read moresusceptibility to recurrent pregnancy loss can be caused by variation in
the ANXA5 gene (131230) on chromosome 4q26-q28.
For a discussion of genetic heterogeneity of susceptibility to recurrent
pregnancy loss, see RPRGL1 (614389).
DESCRIPTION
Miscarriage, the commonest complication of pregnancy, is the spontaneous
loss of a pregnancy before the fetus has reached viability. The term
therefore includes all pregnancy losses from the time of conception
until 24 weeks of gestation. Recurrent miscarriage, defined as 3 or more
consecutive pregnancy losses, affects about 1% of couples; when defined
as 2 or more losses, the scale of the problem increases to 5% of all
couples trying to conceive (summary by Rai and Regan, 2006).
Pregnancy losses have traditionally been designated 'spontaneous
abortions' if they occur before 20 weeks' gestation and 'stillbirths' if
they occur after 20 weeks. Subtypes of spontaneous abortions can be
further distinguished on the basis of embryonic development and include
anembryonic loss in the first 5 weeks after conception (so-called
'blighted ovum'), embryonic loss from 6 to 9 weeks' gestation, and fetal
loss from 10 weeks' gestation through the remainder of the pregnancy.
These distinctions are important because the causes of pregnancy loss
vary over gestational ages, with anembryonic losses being more likely to
be associated with chromosomal abnormalities, for example. Possible
etiologies for recurrent pregnancy loss include uterine anatomic
abnormalities, cytogenetic abnormalities in the parents or fetus, single
gene disorders, thrombophilic conditions, and immunologic or endocrine
factors as well as environmental or infectious agents (summary by Warren
and Silver, 2008).
MOLECULAR GENETICS
In 70 German patients with recurrent pregnancy loss (RPRGL) who were
known to carry neither factor V Leiden (612309.0001) nor the 20210G-A
prothrombin mutation (176930.0009), Bogdanova et al. (2007) analyzed the
gene encoding the placental anticoagulant protein annexin A5 (ANXA5;
131230). They identified 4 consecutive nucleotide substitutions in the
promoter region that were transmitted as a joint haplotype that they
designated 'M2' (131230.0001). Carriers of the M2 haplotype had a
greater than 2-fold higher risk of RPRGL than noncarriers (odds ratio,
2.42) when using unselected controls; when compared to women with
successful pregnancies and no previous history of pregnancy loss,
carriers had an almost 4-fold higher risk of RPRGL (odds ratio, 3.88).
*FIELD* RF
1. Bogdanova, N.; Horst, J.; Chlystun, M.; Croucher, P. J. P.; Nebel,
A.; Bohring, A.; Todorova, A.; Schreiber, S.; Gerke, V.; Krawczak,
M.; Markoff, A.: A common haplotype of the annexin A5 (ANXA5) gene
promoter is associated with recurrent pregnancy loss. Hum. Molec.
Genet. 16: 573-578, 2007.
2. Rai, R.; Regan, L.: Recurrent miscarriage. Lancet 368: 601-611,
2006.
3. Warren, J. E.; Silver, R. M.: Genetics of pregnancy loss. Clin.
Obstet. Gynec. 51: 84-95, 2008.
*FIELD* CS
INHERITANCE:
Autosomal dominant
GENITOURINARY:
[Internal genitalia, female];
Spontaneous abortion, recurrent
MOLECULAR BASIS:
Caused by mutation in the annexin A5 gene (ANXA5, 131230.0001)
*FIELD* CD
Marla J. F. O'Neill: 12/13/2011
*FIELD* ED
joanna: 12/13/2011
*FIELD* CD
Marla J. F. O'Neill: 12/12/2011
*FIELD* ED
alopez: 12/13/2011