Reviewed, UniProtKB/Swiss-Prot P08758 (ANXA5_HUMAN)

Names and origin

Protein names

Recommended name:
    Annexin A5
Alternative name(s):
    Annexin-5
    Annexin V
    Lipocortin V
    Endonexin II
    Calphobindin I
      Short name=CBP-I
    Placental anticoagulant protein I
      Short name=PAP-I
    Placental anticoagulant protein 4
      Short name=PP4
    Thromboplastin inhibitor
    Vascular anticoagulant-alpha
      Short name=VAC-alpha
    Anchorin CII

Gene names

Name:	ANXA5
Synonyms:	ANX5, ENX2, PP4

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	320 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	This protein is an anticoagulant protein that acts as an indirect inhibitor of the thromboplastin-specific complex, which is involved in the blood coagulation cascade.
Subunit structure	Monomer. Binds ATRX By similarity.
Domain	A pair of annexin repeats may form one binding site for calcium and phospholipid.
Sequence similarities	Belongs to the annexin family. Contains 4 annexin repeats.
Caution	This protein has been independently sequenced by at least seven groups under different names. Ref.9 sequence was thought to originate from mouse.

Ontologies

Keywords
Biological process	Blood coagulation
Domain	Annexin Repeat
Ligand	Calcium Calcium/phospholipid-binding
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	anti-apoptosis Traceable author statement. Source: UniProtKB signal transduction Traceable author statement. Source: UniProtKB
Cellular component	cytoplasm Traceable author statement. Source: UniProtKB
Molecular function	phospholipase inhibitor activity Ref.6 Traceable author statement. Source: ProtInc phospholipid binding Ref.4 Traceable author statement. Source: ProtInc protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Abp10	P70489	1	EBI-296601,EBI-78367	From a different organism.
Atrx	P70486	1	EBI-296601,EBI-78333	From a different organism.
Dnmt1	Q9Z330	1	EBI-296601,EBI-78342	From a different organism.
Eif5b	P70488	1	EBI-296601,EBI-78359	From a different organism.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Molecule processing

Initiator methionine

1

1

Removed

Chain

2 – 320

319

Annexin A5

Regions

Repeat

24 – 84

61

Annexin 1

Repeat

96 – 156

61

Annexin 2

Repeat

180 – 240

61

Annexin 3

Repeat

255 – 315

61

Annexin 4

Amino acid modifications

Modified residue

2

1

N-acetylalanine

Modified residue

94

1

Phosphotyrosine

Modified residue

101

1

N6-acetyllysine

Experimental info

Sequence conflict

135

1

S → L in CAG38759. Ref.9

Sequence conflict

279

1

I → T in AAH18671. Ref.10

Secondary structure

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320

Helix Strand Turn

Details...

Helix

17 – 28

12

Beta strand

29 – 32

4

Helix

35 – 42

8

Helix

47 – 61

15

Helix

65 – 72

8

Helix

75 – 85

11

Helix

88 – 99

12

Helix

102 – 104

3

Helix

107 – 116

10

Helix

119 – 133

15

Helix

137 – 144

8

Helix

147 – 157

11

Helix

169 – 184

16

Turn

185 – 187

3

Helix

191 – 200

10

Helix

203 – 215

13

Helix

221 – 224

4

Turn

227 – 229

3

Helix

232 – 245

14

Helix

247 – 257

11

Beta strand

260 – 263

4

Helix

266 – 275

10

Turn

276 – 280

5

Helix

281 – 292

12

Helix

296 – 303

8

Helix

306 – 316

11

Sequences

	Sequence		Length	Mass (Da)
	P08758-1 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 45E14E3964BA4D1A	FASTA	320	35,937
	10 20 30 40 50 60 MAQVLRGTVT DFPGFDERAD AETLRKAMKG LGTDEESILT LLTSRSNAQR QEISAAFKTL 70 80 90 100 110 120 FGRDLLDDLK SELTGKFEKL IVALMKPSRL YDAYELKHAL KGAGTNEKVL TEIIASRTPE 130 140 150 160 170 180 ELRAIKQVYE EEYGSSLEDD VVGDTSGYYQ RMLVVLLQAN RDPDAGIDEA QVEQDAQALF 190 200 210 220 230 240 QAGELKWGTD EEKFITIFGT RSVSHLRKVF DKYMTISGFQ IEETIDRETS GNLEQLLLAV 250 260 270 280 290 300 VKSIRSIPAY LAETLYYAMK GAGTDDHTLI RVMVSRSEID LFNIRKEFRK NFATSLYSMI 310 320 KGDTSGDYKK ALLLLCGEDD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Primary structure of human placental anticoagulant protein." Funakoshi T., Hendrickson L.E., McMullen B.A., Fujikawa K. Biochemistry 26:8087-8092(1987) [PubMed: 2964863] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Structure and expression of cDNA for an inhibitor of blood coagulation isolated from human placenta: a new lipocortin-like protein." Iwasaki A., Suda M., Nakao H., Nagoya T., Saino Y., Arai K., Mizoguchi T., Sato F., Yoshizaki H., Hirata M., Miyata T., Shidara Y., Murata M., Maki M. J. Biochem. 102:1261-1273(1987) [PubMed: 2963810] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 2-320.
[3]	"Cloning and expression of cDNA for human vascular anticoagulant, a Ca2+-dependent phospholipid-binding protein." Maurer-Fogy I., Reutelingsperger C.P.M., Pieters J., Bodo G., Stratowa C., Hauptmann R. Eur. J. Biochem. 174:585-592(1988) [PubMed: 2455636] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
[4]	"Cloning and expression of cDNA for human endonexin II, a Ca2+ and phospholipid binding protein." Kaplan R., Jaye M., Burgess W.H., Schlaepfer D.D., Haigler H.T. J. Biol. Chem. 263:8037-8043(1988) [PubMed: 2967291] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]	"Five distinct calcium and phospholipid binding proteins share homology with lipocortin I." Pepinsky R.B., Tizard R., Mattaliano R.J., Sinclair L.K., Miller G.T., Browning J.L., Chow E.P., Burne C., Huang K.-S., Pratt D., Wachter L., Hession C., Frey A.Z., Wallner B.P. J. Biol. Chem. 263:10799-10811(1988) [PubMed: 2968983] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[6]	"Characterization of cDNA encoding human placental anticoagulant protein (PP4): homology with the lipocortin family." Grundmann U., Abel K.-J., Bohn H., Loebermann H., Lottspeich F., Kuepper H. Proc. Natl. Acad. Sci. U.S.A. 85:3708-3712(1988) [PubMed: 2967495] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[7]	"The gene encoding human annexin V has a TATA-less promoter with a high G+C content." Fernandez M.-P., Morgan R.O., Fernandez M.R., Carcedo M.-T. Gene 149:253-260(1994) [PubMed: 7958998] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Lung.
[8]	"Organization of the human annexin V (ANX5) gene." Cookson B.T., Engelhardt S., Smith C., Bamford H.A., Prochazka M., Tait J.F. Genomics 20:463-467(1994) [PubMed: 8034319] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[9]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[10]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Muscle, Ovary and Skin.
[11]	"A 32 kDa lipocortin from human mononuclear cells appears to be identical with the placental inhibitor of blood coagulation." Rothhut R., Comera C., Cortial S., Haumont P.-Y., Diep Le K.H., Cavadore J.-C., Conard J., Russo-Marie F., Lederer F. Biochem. J. 263:929-935(1989) [PubMed: 2532007] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE.
[12]	Quadroni M., Potts A., Barblan J., Bienvenut W.V. Submitted (JAN-2005) to UniProtKB Cited for: PROTEIN SEQUENCE OF 7-18; 30-45; 187-201 AND 277-286, MASS SPECTROMETRY. Tissue: Melanoma.
[13]	"Structural and functional characterization of endonexin II, a calcium- and phospholipid-binding protein." Schlaepfer D.D., Mehlman T., Burgess W.H., Haigler H.T. Proc. Natl. Acad. Sci. U.S.A. 84:6078-6082(1987) [PubMed: 2957692] [Abstract] Cited for: PROTEIN SEQUENCE OF 86-131; 259-297 AND 300-320.
[14]	"Sedimentation equilibrium analysis of five lipocortin-related phospholipase A2 inhibitors from human placenta. Evidence against a mechanistically relevant association between enzyme and inhibitor." Ahn N.G., Teller D.C., Bienkowski M.J., McMullen B.A., Lipkin E.W., de Haen C. J. Biol. Chem. 263:18657-18663(1988) [PubMed: 2974032] [Abstract] Cited for: PROTEIN SEQUENCE OF 85-93.
[15]	"Vectorial proteomics reveal targeting, phosphorylation and specific fragmentation of polymerase I and transcript release factor (PTRF) at the surface of caveolae in human adipocytes." Aboulaich N., Vainonen J.P., Stralfors P., Vener A.V. Biochem. J. 383:237-248(2004) [PubMed: 15242332] [Abstract] Cited for: PROTEIN SEQUENCE OF 152-161 AND 246-260. Tissue: Adipocyte.
[16]	"Substrate and functional diversity of lysine acetylation revealed by a proteomics survey." Kim S.C., Sprung R., Chen Y., Xu Y., Ball H., Pei J., Cheng T., Kho Y., Xiao H., Xiao L., Grishin N.V., White M., Yang X.-J., Zhao Y. Mol. Cell 23:607-618(2006) [PubMed: 16916647] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-101, MASS SPECTROMETRY. Tissue: Epithelium.
[17]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-94, MASS SPECTROMETRY.
[18]	"The crystal and molecular structure of human annexin V, an anticoagulant protein that binds to calcium and membranes." Huber R., Roemisch J., Paques E.-P. EMBO J. 9:3867-3874(1990) [PubMed: 2147412] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
[19]	"The calcium binding sites in human annexin V by crystal structure analysis at 2.0-A resolution. Implications for membrane binding and calcium channel activity." Huber R., Schneider M., Mayr I., Roemisch J., Paques E.-P. FEBS Lett. 275:15-21(1990) [PubMed: 2148156] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
[20]	"Crystal and molecular structure of human annexin V after refinement. Implications for structure, membrane binding and ion channel formation of the annexin family of proteins." Huber R., Berendes R., Burger A., Schneider M., Karshikov A., Luecke H., Roemisch J., Paques E.-P. J. Mol. Biol. 223:683-704(1992) [PubMed: 1311770] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
[21]	"Crystal structure of annexin V with its ligand K-201 as a calcium channel activity inhibitor." Kaneko N., Ago H., Matsuda R., Inagaki E., Miyano M. J. Mol. Biol. 274:16-20(1997) [PubMed: 9398511] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS).
[22]	"Residue-specific bioincorporation of non-natural, biologically active amino acids into proteins as possible drug carriers: structure and stability of the per-thiaproline mutant of annexin V." Budisa N., Minks C., Medrano F.J., Lutz J., Huber R., Moroder L. Proc. Natl. Acad. Sci. U.S.A. 95:455-459(1998) [PubMed: 9435213] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
+	Additional computationally mapped references.

Web resources

R&D Systems' cytokine source book: Annexin V

Cross-references

Sequence databases

EMBLGenBankDDBJ

M18366 mRNA. Translation: AAA35570.1.
D00172 mRNA. Translation: BAA00122.1.
X12454 mRNA. Translation: CAA30985.1.
J03745 mRNA. Translation: AAA52386.1.
M21731 mRNA. Translation: AAA36166.1.
M19384 mRNA. Translation: AAB59545.1.
U01691 , U01681, U01682, U01683, U01685, U01686, U01687, U01689, U01690 Genomic DNA. Translation: AAB40047.1.
U05770 , U05760, U05761, U05762, U05764, U05765, U05766, U05767, U05768, U05769 Genomic DNA. Translation: AAB60648.1.
CR536522 mRNA. Translation: CAG38759.1.
BC001429 mRNA. Translation: AAH01429.1.
BC004993 mRNA. Translation: AAH04993.1.
BC012804 mRNA. Translation: AAH12804.1.
BC012822 mRNA. Translation: AAH12822.1.
BC018671 mRNA. Translation: AAH18671.1.

PIR

AQHUP. D29250.

RefSeq

NP_001145.1.

UniGene

Hs.480653
Hs.658778

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1ANW	X-ray	2.40	A/B	1-320	[»]
1ANX	X-ray	1.90	A/B/C	1-320	[»]
1AVH	X-ray	2.30	A/B	1-320	[»]
1AVR	X-ray	2.30	A	1-320	[»]
1HAK	X-ray	3.00	A/B	1-320	[»]
1HVD	X-ray	2.00	A	1-320	[»]
1HVE	X-ray	2.30	A	1-320	[»]
1HVF	X-ray	2.00	A	1-320	[»]
1HVG	X-ray	3.00	A	1-320	[»]
1SAV	X-ray	2.50	A	1-320	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P08758.

PTM databases

PhosphoSite

P08758.

2-D gel databases