Reviewed, UniProtKB/Swiss-Prot P07355 (ANXA2_HUMAN)

Names and origin

Protein names

Recommended name:
    Annexin A2
Alternative name(s):
    Annexin-2
    Annexin II
    Lipocortin II
    Calpactin I heavy chain
    Chromobindin-8
    p36
    Protein I
    Placental anticoagulant protein IV
      Short name=PAP-IV

Gene names

Name:	ANXA2
Synonyms:	ANX2, ANX2L4, CAL1H, LPC2D

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	339 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	Calcium-regulated membrane-binding protein whose affinity for calcium is greatly enhanced by anionic phospholipids. It binds two calcium ions with high affinity. May be involved in heat-stress response.
Subunit structure	Heterotetramer containing 2 light chains of S100A10/p11 and 2 heavy chains of ANXA2/p36. Interacts with ATP1B1 and DYSF By similarity.
Subcellular location	Secreted › extracellular space › extracellular matrix › basement membrane. Melanosome. Note: In the lamina beneath the plasma membrane. Identified by mass spectrometry in melanosome fractions from stage I to stage IV. Translocated from the cytoplasm to the cell surface through a Golgi-independent mechanism. Ref.14
Domain	A pair of annexin repeats may form one binding site for calcium and phospholipid.
Post-translational modification	Phosphorylation of Tyr-24 enhances heat stress-induced translocation to the cell surface.
Miscellaneous	It may cross-link plasma membrane phospholipids with actin and the cytoskeleton and be involved with exocytosis.
Sequence similarities	Belongs to the annexin family. Contains 4 annexin repeats.

Ontologies

Keywords
Cellular component	Basement membrane Extracellular matrix Secreted
Coding sequence diversity	Polymorphism
Domain	Annexin Repeat
Ligand	Calcium Calcium/phospholipid-binding
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	skeletal system development Traceable author statement. Source: ProtInc
Cellular component	basement membrane Inferred from electronic annotation. Source: UniProtKB-SubCell extracellular space Inferred from electronic annotation. Source: UniProtKB-SubCell melanosome Inferred from electronic annotation. Source: UniProtKB-SubCell soluble fraction Traceable author statement. Source: ProtInc
Molecular function	calcium ion binding Inferred from electronic annotation. Source: UniProtKB-KW calcium-dependent phospholipid binding Inferred from electronic annotation. Source: UniProtKB-KW cytoskeletal protein binding Inferred from electronic annotation. Source: InterPro phospholipase inhibitor activity Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PPM1B	O75688	1	EBI-352622,EBI-1047039

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.5

Chain

2 – 339

338

Annexin A2

PRO_0000067470

Regions

Repeat

42 – 102

61

Annexin 1

Repeat

114 – 174

61

Annexin 2

Repeat

199 – 259

61

Annexin 3

Repeat

274 – 334

61

Annexin 4

Region

2 – 24

23

S100A10-binding site Potential

Amino acid modifications

Modified residue

2

1

N-acetylserine Ref.5

Modified residue

18

1

Phosphoserine Ref.15

Modified residue

19

1

Phosphothreonine Ref.13 Ref.17

Modified residue

24

1

Phosphotyrosine; by SRC Ref.11 Ref.16 Ref.18

Modified residue

26

1

Phosphoserine; by PKC Ref.10

Modified residue

30

1

Phosphotyrosine Ref.16 Ref.12

Modified residue

188

1

Phosphotyrosine Ref.16

Modified residue

199

1

Phosphotyrosine Ref.16

Modified residue

238

1

Phosphotyrosine Ref.16

Modified residue

316

1

Phosphotyrosine Ref.16

Modified residue

317

1

Phosphotyrosine Ref.16

Modified residue

318

1

Phosphotyrosine Ref.16

Natural variations

Natural variant

98

1

V → L Ref.4

VAR_012982

Experimental info

Mutagenesis

24

1

Y → A: Abolishes heat stress-induced cell surface localization. Ref.11

Sequence conflict

29

1

A → P AA sequence Ref.7

Secondary structure

1

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339

Helix Strand Turn

Details...

Helix

35 – 47

13

Helix

53 – 60

8

Helix

65 – 79

15

Helix

83 – 90

8

Helix

93 – 103

11

Helix

106 – 117

12

Helix

125 – 134

10

Helix

137 – 151

15

Helix

155 – 161

7

Helix

165 – 175

11

Helix

188 – 200

13

Turn

201 – 204

4

Beta strand

205 – 207

3

Helix

210 – 219

10

Helix

222 – 232

11

Turn

233 – 235

3

Helix

240 – 247

8

Helix

250 – 264

15

Helix

266 – 278

13

Beta strand

279 – 282

4

Helix

285 – 295

11

Turn

296 – 298

3

Helix

300 – 311

12

Helix

315 – 322

8

Helix

325 – 335

11

Sequences

	Sequence		Length	Mass (Da)
	P07355-1 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 5126E1337A0CBEA1	FASTA	339	38,604
	10 20 30 40 50 60 MSTVHEILCK LSLEGDHSTP PSAYGSVKAY TNFDAERDAL NIETAIKTKG VDEVTIVNIL 70 80 90 100 110 120 TNRSNAQRQD IAFAYQRRTK KELASALKSA LSGHLETVIL GLLKTPAQYD ASELKASMKG 130 140 150 160 170 180 LGTDEDSLIE IICSRTNQEL QEINRVYKEM YKTDLEKDII SDTSGDFRKL MVALAKGRRA 190 200 210 220 230 240 EDGSVIDYEL IDQDARDLYD AGVKRKGTDV PKWISIMTER SVPHLQKVFD RYKSYSPYDM 250 260 270 280 290 300 LESIRKEVKG DLENAFLNLV QCIQNKPLYF ADRLYDSMKG KGTRDKVLIR IMVSRSEVDM 310 320 330 LKIRSEFKRK YGKSLYYYIQ QDTKGDYQKA LLYLCGGDD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Two human 35 kd inhibitors of phospholipase A2 are related to substrates of pp60v-src and of the epidermal growth factor receptor/kinase." Huang K.-S., Wallner B.P., Mattaliano R.J., Tizard R., Burne C., Frey A., Hession C., McGray P., Sinclair L.K., Chow E.P., Browning J.L., Ramachandran K.L., Tang J., Smart J.E., Pepinsky R.B. Cell 46:191-199(1986) [PubMed: 3013422] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Placenta.
[2]	"Characterization of the human lipocortin-2-encoding multigene family: its structure suggests the existence of a short amino acid unit undergoing duplication." Spano F., Raugei G., Palla E., Colella C., Melli M. Gene 95:243-251(1990) [PubMed: 2174397] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"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], VARIANT LEU-98. Tissue: Brain, Colon, Pancreas, Prostate, Skin and Testis.
[5]	Bienvenut W.V., Murray L., Brunton V.G., Frame M.C., Bensaad K., Vousden K.H. Submitted (FEB-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-10; 38-47; 50-63; 69-77; 89-115; 153-169 AND 213-220, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT SER-2, MASS SPECTROMETRY. Tissue: Colon adenocarcinoma and Osteosarcoma.
[6]	"The protein-tyrosine kinase substrate, calpactin I heavy chain (p36), is part of the primer recognition protein complex that interacts with DNA polymerase alpha." Jindal H.K., Chaney W.G., Anderson C.W., Davis R.G., Vishwanatha J.K. J. Biol. Chem. 266:5169-5176(1991) [PubMed: 1825830] [Abstract] Cited for: PROTEIN SEQUENCE OF 11-27; 49-62; 68-77; 120-135; 314-323 AND 329-339.
[7]	"Identification and characterization of alpha-protein kinase C binding proteins in normal and transformed REF52 cells." Hyatt S.L., Liao L., Chapline C., Jaken S. Biochemistry 33:1223-1228(1994) [PubMed: 8110754] [Abstract] Cited for: PROTEIN SEQUENCE OF 15-40 AND 50-63.
[8]	"An endothelial cell-surface form of annexin II binds human cytomegalovirus." Wright J.F., Kurosky A., Wasi S. Biochem. Biophys. Res. Commun. 198:983-989(1994) [PubMed: 8117306] [Abstract] Cited for: PROTEIN SEQUENCE OF 18-37; 119-126; 172-191 AND 301-307.
[9]	"Annexin II is a major component of fusogenic endosomal vesicles." Emans N., Gorvel J.P., Walter C., Gerke V., Kellner R., Griffiths G., Gruenberg J. J. Cell Biol. 120:1357-1369(1993) [PubMed: 8449982] [Abstract] Cited for: PROTEIN SEQUENCE OF 234-241 AND 252-261.
[10]	"The protein-tyrosine kinase substrate p36 is also a substrate for protein kinase C in vitro and in vivo." Gould K.L., Woodgett J.R., Isacke C.M., Hunter T. Mol. Cell. Biol. 6:2738-2744(1986) [PubMed: 2946940] [Abstract] Cited for: PHOSPHORYLATION AT SER-26.
[11]	"An annexin 2 phosphorylation switch mediates p11-dependent translocation of annexin 2 to the cell surface." Deora A.B., Kreitzer G., Jacovina A.T., Hajjar K.A. J. Biol. Chem. 279:43411-43418(2004) [PubMed: 15302870] [Abstract] Cited for: PHOSPHORYLATION AT TYR-24, MUTAGENESIS OF TYR-24.
[12]	"Time-resolved mass spectrometry of tyrosine phosphorylation sites in the epidermal growth factor receptor signaling network reveals dynamic modules." Zhang Y., Wolf-Yadlin A., Ross P.L., Pappin D.J., Rush J., Lauffenburger D.A., White F.M. Mol. Cell. Proteomics 4:1240-1250(2005) [PubMed: 15951569] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-30, MASS SPECTROMETRY. Tissue: Epithelium.
[13]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-19, MASS SPECTROMETRY. Tissue: Epithelium.
[14]	"Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes." Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F. J. Proteome Res. 5:3135-3144(2006) [PubMed: 17081065] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[15]	"Phosphoproteome analysis of the human mitotic spindle." Nousiainen M., Sillje H.H.W., Sauer G., Nigg E.A., Koerner R. Proc. Natl. Acad. Sci. U.S.A. 103:5391-5396(2006) [PubMed: 16565220] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-18, MASS SPECTROMETRY. Tissue: Epithelium.
[16]	"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-24; TYR-30; TYR-188; TYR-199; TYR-238; TYR-316; TYR-317 AND TYR-318, MASS SPECTROMETRY.
[17]	"Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra." Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D. J. Proteome Res. 6:4150-4162(2007) [PubMed: 17924679] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-19, MASS SPECTROMETRY. Tissue: Epithelium.
[18]	"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry." Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A. Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-24, MASS SPECTROMETRY.
[19]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[20]	"The crystal structure and ion channel activity of human annexin II, a peripheral membrane protein." Burger A., Berendes R., Liemann S., Benz J., Hofmann A., Goettig P., Huber R., Gerke V., Tiel C., Roemisch J., Weber K. J. Mol. Biol. 257:839-847(1996) [PubMed: 8636985] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
+	Additional computationally mapped references.

Web resources

Protein Spotlight

Red velvet - Issue 86 of September 2007

Cross-references

Sequence databases

EMBLGenBankDDBJ

D00017 mRNA. Translation: BAA00013.1.
BT007432 mRNA. Translation: AAP36100.1.
BC001388 mRNA. Translation: AAH01388.1.
BC009564 mRNA. Translation: AAH09564.1.
BC015834 mRNA. Translation: AAH15834.1.
BC016774 mRNA. Translation: AAH16774.1.
BC021114 mRNA. Translation: AAH21114.1.
BC052558 mRNA. Translation: AAH52558.1.
BC052567 mRNA. Translation: AAH52567.1.
BC066955 mRNA. Translation: AAH66955.2. Different initiation.
BC068065 mRNA. Translation: AAH68065.1.
BC093056 mRNA. Translation: AAH93056.1.

IPI

IPI00455315.

PIR

LUHU36. A23942.

RefSeq

NP_001002857.1.
NP_001129487.1.
NP_004030.1.

UniGene

Hs.511605

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1W7B	X-ray	1.52	A	1-339	[»]
1XJL	X-ray	2.59	A/B	21-338	[»]
2HYU	X-ray	1.86	A	32-338	[»]
2HYV	X-ray	1.42	A	32-338	[»]
2HYW	X-ray	2.10	A/B	32-338	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P07355. 21 interactions.

PTM databases

PhosphoSite

P07355.

2-D gel databases

Cornea-2DPAGE

P07355.

DOSAC-COBS-2DPAGE

P07355.

REPRODUCTION-2DPAGE

IPI00455315.
P07355.

Proteomic databases

PRIDE

P07355.

Genome annotation databases

Ensembl

ENSG00000182718. Homo sapiens. [Contig view]

GeneID

302.

KEGG

hsa:302.

Organism-specific databases

GeneCards

GC15M058426.

H-InvDB

HIX0012298.

HGNC

HGNC:537. ANXA2.

HPA

CAB004311.

MIM

151740. gene.

PharmGKB

PA24827.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P07355.

Gene expression databases

ArrayExpress

P07355.

Bgee

P07355.

CleanEx

HS_ANXA2.

GermOnline

ENSG00000182718. Homo sapiens.

Family and domain databases

InterPro

IPR001464. Annexin.
IPR018502. Annexin_repeat.
IPR018252. Annexin_repeat_CS.
IPR002389. AnnexinII.
[Graphical view]

Gene3D

G3DSA:1.10.220.10. Annexin. 4 hits.

PANTHER

PTHR10502. Annexin. 1 hit.
PTHR10502:SF18. AnnexinII. 1 hit.

Pfam

PF00191. Annexin. 4 hits.
[Graphical view]

PRINTS

PR00196. ANNEXIN.
PR00198. ANNEXINII.

ProDom

PD000143. Annexin. 4 hits.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00335. ANX. 4 hits.
[Graphical view]

PROSITE

PS00223. ANNEXIN. 4 hits.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00009. Alteplase.
DB00029. Anistreplase.
DB00031. Tenecteplase.

NextBio

1217.

SOURCE

Search...

Entry information

Entry name

ANXA2_HUMAN

Accession

Primary (citable) accession number: P07355
Secondary accession number(s): Q567R4, Q96DD5

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1988
Last sequence update:	January 23, 2007
Last modified:	June 16, 2009
This is version 123 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)